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S1 Diabetes Care Volume 37, Supplement 1, January 2014

414

Standards of Medical Care in American Diabetes Association

Diabetesd2014
Diabetes mellitus is a complex, chronic illness requiring continuous medical
care with multifactorial risk reduction strategies beyond glycemic control.
Ongoing
patient self-management education and support are critical to preventing acute
complications and reducing the risk of long-term complications. Signicant
evidence exists that supports a range of interventions to improve diabetes
outcomes.
The American Diabetes Associations (ADAs) Standards of Care are intended to
provide clinicians, patients, researchers, payers, and other interested
individuals with the components of diabetes care, general treatment goals,
POSITION STATEMENT

and tools to evaluate the quality of care. The Standards of Care


recommendations are not intended to preclude clinical judgment and must be
applied in the context of excellent clinical care and with adjustments for
individual preferences, comorbidities, and other patient factors. For
more detailed information about management of diabetes, refer to
references 1,2.
The recommendations include screening, diagnostic, and therapeutic actions
that are known or believed to favorably affect health outcomes of patients with
diabetes. Many of these interventions have also been shown to be cost-effective
(3). A grading system (Table 1) developed by ADA and modeled after existing
methods was used to clarify and codify the evidence that forms the basis for the
recommendations. The letters A, B, C, or E show the evidence level that supports
each recommendation. The Standards of Care conclude with evidence and
recommendations for strategies to improve the process of diabetes care. It must
be emphasized that clinical evidence and expert recommendations alone cannot
improve patients lives, but must be effectively translated into clinical
management.

I. CLASSIFICATION AND DIAGNOSIS


A. Classication
Diabetes can be classied into four clinical categories:

c Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin


deciency)
c Type 2 diabetes (due to a progressive insulin secretory defect on the background
of insulin resistance)
c Other specic types of diabetes due to other causes, e.g., genetic defects in b-
cell function, genetic defects in insulin action, diseases of the exocrine pancreas
(such as cystic brosis), and drug- or chemical-induced (such as in the treatment
of HIV/ AIDS or after organ transplantation)
c Gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy that
is not clearly overt diabetes)

Some patients cannot be clearly classied as type 1 or type 2 diabetic.


Clinical presentation and disease progression vary considerably in both types of
diabetes. Occasionally, patients diagnosed with type 2 diabetes may present
with ketoacidosis. Children with type 1 diabetes typically present with the Originally approved 1988. Most recent review/
revision October 2013.
hallmark symptoms of polyuria/polydipsia and occasionally with diabetic
DOI: 10.2337/dc14-S014
ketoacidosis (DKA). However, difculties in diagnosis may occur in children,
2014 by the American Diabetes
adolescents, and adults, with the true diagnosis becoming more obvious Association. See
over time. http://creativecommons.org/licenses/by- nc-
S1 Diabetes Care Volume 37, Supplement 1, January 2014
nd515
/3.0/ for details.
Table 1ADA evidence grading system for Clinical Practice Recommendations abnormal hemoglobins should be used.
Level of
An updated list is available at
ev id enc e Des cr ip t io n www.ngsp. org/interf.asp. In situations
of abnormal red cell turnover, such as
A Clear evidence from well-conducted, generalizable RCTs that are adequately
powered, including:
pregnancy, recent blood loss or
c Evidence from a well-conducted multicenter trial transfusion, or some anemias, only
c Evidence from a meta-analysis that incorporated quality ratings in the analysis blood glucose criteria should be used to
Compelling nonexperimental evidence, i.e., all or none rule developed diagnose diabetes.
by the Center for Evidence-Based Medicine at the University of Oxford
Supportive evidence from well-conducted RCTs that are adequately powered, cell turnover, such as sickle cell trait, an A1C
including: assay without interference from
c Evidence from a well-conducted trial at one or more institutions
c Evidence from a meta-analysis that incorporated quality ratings in the analysis
B Supportive evidence from well-conducted cohort studies
c Evidence from a well-conducted prospective cohort study or registry
c Evidence from a well-conducted meta-analysis of cohort studies
Supportive evidence from a well-conducted case-control study
C Supportive evidence from poorly controlled or uncontrolled studies
c Evidence from randomized clinical trials with one or more major or three
or more minor methodological aws that could invalidate the results
c Evidence from observational studies with high potential for bias (such as case
series with comparison with historical controls)
c Evidence from case series or case reports
Conicting evidence with the weight of evidence supporting the recommendation
E Expert consensus or clinical experience

B. Diagnosis of Diabetes cost, the limited availability of A1C


Diabetes is usually diagnosed based on testing in certain regions of the
plasma glucose criteria, either the developing world, and the incomplete
fasting plasma glucose (FPG) or the 2-h correlation between A1C and average
plasma glucose (2-h PG) value after a glucose in certain individuals.
75-g oral glucose tolerance test (OGTT)
Race/Ethnicity
(4). Recently, an International Expert
Committee added the A1C (threshold A1C levels may vary with patients race/
$6.5%) as a third option to diagnose ethnicity (6,7). Glycation rates may differ
diabetes (5) (Table 2). by race. For example, African Americans
may have higher rates of glycation, but
A1C this is controversial. A recent
The A1C test should be performed epidemiological study found that, when
using a method that is certied by the matched for FPG, African Americans
National Glycohemoglobin (with and without diabetes) had higher
Standardization Program (NGSP) and A1C than non- Hispanic whites, but also
standardized or traceable to the had higher levels of fructosamine and
Diabetes Control and Complications glycated albumin and lower levels of 1,5
Trial (DCCT) reference assay. Although anhydroglucitol, suggesting that their
point-of-care (POC) A1C assays may be glycemic burden (particularly
NGSP-certied, prociency testing is not postprandially) may be higher (8).
mandated for performing the test, so Epidemiological studies forming the
use of these assays for diagnostic framework for recommending A1C to
purposes may be problematic. diagnose diabetes have all been in adult
Epidemiological data show a similar populations. It is unclear if the same
relationship of A1C with the risk of A1C cut point should be used to
retinopathy as seen with FPG and 2-h diagnose children or adolescents with
PG. The A1C has several advantages to diabetes (9,10).
the FPG and OGTT, including greater Anemias/Hemoglobinopathies
convenience (fasting not required), Interpreting A1C levels in the presence
possibly greater preanalytical stability, of certain anemias and
and less day-to-day perturbations hemoglobinopathies is particularly
during stress and illness. These problematic. For patients with an
advantages must be balanced by greater abnormal hemoglobin but normal red
Fasting and Two-Hour Plasma
Glucose
In addition to the A1C test, the FPG and
2-h PG may also be used to
diagnose diabetes. The current
diagnostic criteria for diabetes
are summarized in Table 2. The
concordance between the FPG
and
2-h PG tests is ,100%. The
concordance between A1C and
either glucose-based test is also
imperfect. National Health and
Nutrition Examination Survey
(NHANES) data indicate that the
A1C cut point of
$6.5% identies one-third fewer
cases of undiagnosed diabetes
than a fasting glucose cut point of
$126 mg/dL (7.0 mmol/L) (11).
Numerous studies have conrmed
that, at these cut points, the
2-h OGTT value diagnoses more
screened people with diabetes
(12). In reality, a large portion of
the diabetic population remains
undiagnosed. Of note, the lower
sensitivity of A1C at the
designated cut point may be
offset by the tests ability to
facilitate the diagnosis.
As with most diagnostic tests, a
test result should be repeated
when feasible
Table 2Criteria for the diagnosis of
diabetes
A1C $6.5%. The test should be performed
in a laboratory using a method that is
NGSP certied and standardized to the
DCCT assay.*
OR
FPG $126 mg/dL (7.0 mmol/L). Fasting
is dened as no caloric intake for at
least 8 h.*
OR
Two-hour PG $200 mg/dL (11.1 mmol/L)
during an OGTT. The test should be
performed as described by the WHO,
using a glucose load containing the
equivalent of 75 g anhydrous glucose
dissolved in water.*
OR
In a patient with classic symptoms of
hyperglycemia or hyperglycemic crisis,
a random plasma glucose $200 mg/dL
(1 1. 1 mm ol /L ).
*In the absence of unequivocal
hyperglycemia, result should be conrmed
by repeat testing.
S1616 Position Diabetes Care Volume 37, Supplement 1, January 2014
Statement

to rule out laboratory error (e.g., an 140199 mg/dL [7.811.0 Prediabetes is the term used for
elevated A1C should be repeated when mmol/L]). individuals with IFG and/or IGT, indicating
feasible, and not necessarily in 3 It should be noted that the the relatively high risk for the future
months). Unless there is a clear clinical World Health Organization development of diabetes. IFG and IGT
diagnosis (e.g., a patient in a (WHO) and a number of other should not be viewed as clinical entities
hyperglycemic crisis or classic symptoms diabetes organizations dene in their own right but rather risk factors
of hyperglycemia and a random plasma the cutoff for IFG at 110 mg/dL for diabetes and cardiovascular disease
glucose $200 mg/dL), it is preferable (6.1 mmol/L). (CVD). IFG and IGT are associated with
that the same test be repeated for obesity (especially
conrmation, since there will be a abdominal or visceral obesity),
greater likelihood of concurrence. For dyslipidemia with high triglycerides
example, if the A1C is and/or low HDL cholesterol, and
7.0% and a repeat result is 6.8%, the hypertension.
diagnosis of diabetes is conrmed. If
two different tests (such as A1C and As with the glucose measures, several
FPG) are both above the diagnostic prospective studies that used A1C to
threshold, this also conrms the predict the progression to diabetes
diagnosis. demonstrated a strong, continuous
association between A1C and subsequent
On the other hand, if a patient has diabetes. In a systematic review of 44,203
discordant results on two different individuals from 16 cohort studies with a
tests, then the test result that is above follow-up interval averaging 5.6 years
the diagnostic cut point should be (range 2.812 years), those with an A1C
repeated. The diagnosis is made on the between 5.5 and 6.0% had a substantially
basis of the conrmed test. For example, increased risk of diabetes (5-year
if a patient meets the diabetes criterion incidences from
of the A1C (two results $6.5%) but not 9 to 25%). An A1C range of 6.06.5%
the FPG (,126 mg/dL or 7.0 mmol/L), had a 5-year risk of developing diabetes
or between 2550%, and a relative risk (RR)
vice versa, that person should be
20 times higher compared with an A1C of
considered to have diabetes.
5.0% (15). In a community-based study of
Since there is preanalytic and analytic African American and non-
variability of all the tests, it is possible Hispanic white adults without diabetes,
that an abnormal result (i.e., above the baseline A1C was a stronger predictor of
diagnostic threshold), when repeated, subsequent diabetes and
will produce a value below the cardiovascular events than fasting
diagnostic cut point. This is least likely glucose (16). Other analyses suggest
for A1C, somewhat more likely for FPG, that an A1C of 5.7% is associated with
and most likely for the 2-h PG. Barring a similar diabetes risk to the high-risk
laboratory error, such patients will likely participants in the Diabetes Prevention
have test results near the margins of the Program (DPP) (17).
diagnostic threshold. The health care
Hence, it is reasonable to consider an
professional might opt to follow the
A1C range of 5.76.4% as identifying
patient closely and repeat the test in 3
individuals with prediabetes. As with
6 months.
those with IFG and IGT, individuals with
C. Categories of Increased Risk for an A1C of 5.76.4% should be informed
Diabetes (Prediabetes) of their increased risk for diabetes and
In 1997 and 2003, the Expert CVD and counseled about effective
Committee on Diagnosis and strategies to lower their risks (see
Classication of Diabetes Mellitus Section IV). Similar to glucose
(13,14) recognized a group of measurements, the continuum of risk is
individuals whose glucose levels did not curvilinear, so as A1C rises, the
meet the criteria for diabetes, but were diabetes risk rises disproportionately
too high to be (15). Aggressive interventions and
considered normal. These persons were vigilant follow-up should be pursued
dened as having impaired fasting for those considered at very high risk
glucose (IFG) (FPG levels 100125 (e.g., those with A1Cs .6.0%). Table 3
mg/dL [5.66.9 mmol/L]), or impaired
summarizes the categories of
glucose tolerance (IGT) (2-h PG OGTT
prediabetes.
values of
care.diabetesjournals.org Position Statement
II. TESTING FOR DIABETES IN S1717
ASYMPTOMATIC PATIENTS
Recommendations
c Testing to detect type 2 diabetes and
prediabetes in asymptomatic people should
be considered in adults of any age who are
overweight or obese (BMI $25 kg/m2) and
who have one or more additional risk
factors for diabetes (Table 4). In those
without these risk factors, testing should
begin at age 45 years. B
c If tests are normal, repeat testing at
least at 3-year intervals is reasonable. E
c To test for diabetes or prediabetes, the
A1C, FPG, or 2-h 75-g OGTT are
appropriate. B
c In those identied with prediabetes,
identify and, if appropriate, treat other
CVD risk factors. B

The same tests are used for both screening


and diagnosing diabetes. Diabetes may be
identied anywhere along the spectrum of
clinical scenarios: from a seemingly low-risk
individual who happens to have glucose
testing, to a higher-risk individual whom the
provider tests because of high suspicion of
diabetes, and nally, to the symptomatic
patient. The discussion herein is primarily
framed as testing for diabetes in asymptomatic
individuals. The same assays used for testing
will also detect individuals with prediabetes.
A. Testing for Type 2 Diabetes and Risk of
Future Diabetes in Adults Prediabetes and
diabetes meet established criteria for
conditions in which early detection is
appropriate.
Both conditions are common, are
increasing in prevalence, and impose

Table 3Categories of increased risk


for diabetes (prediabetes)*
FPG 100 mg/dL (5.6 mmol/L) to 125
mg/dL (6.9 mmol/L) (IFG)
OR
2-h PG in the 75-g OGTT 140 mg/dL
(7.8 mmol/L) to 199 mg/dL
(11.0 mmol/L) (IGT)
OR
A1 C 5. 7 6. 4%
*For all three tests, risk is continuous,
extending below the lower limit of the
range and becoming disproportionately
greater at higher ends of the range.
Table 4Criteria for testing for diabetes in asymptomatic adult individuals risk factors, testing should begin at age
1. Testing should be considered in all adults who are overweight (BMI $25 kg/m2*) and 45 years.
have additional risk factors: The A1C, FPG, or the 2-h OGTT are
c physical inactivity
appropriate for testing. It should be
c rst-degree relative with diabetes
c high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian
noted that the tests do not necessarily
American, Pacic Islander) detect diabetes in the same individuals.
c women who delivered a baby weighing .9 lb or were diagnosed with GDM The efcacy of interventions for primary
c hypertension ($140/90 mmHg or on therapy for hypertension) prevention of type 2 diabetes (2329)
c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level has primarily been demonstrated
.250 mg/dL (2.82 mmol/L) among individuals with IGT, not for
c women with polycystic ovarian syndrome
c A1C $5.7%, IGT, or IFG on previous testing
individuals with isolated IFG or for
c other clinical conditions associated with insulin resistance (e.g., severe obesity, individuals with specic A1C levels.
acanthosis nigricans) Testing Interval
c history of CVD
The appropriate interval between tests
2. In the absence of the above criteria, testing for diabetes should begin at age 45 years.
is not known (30). The rationale for the
3. If results are normal, testing should be repeated at least at 3-year intervals, with 3-year interval is that false negatives
consideration of more frequent testing depending on initial results (e.g., those with
prediabetes should be tested yearly) and risk status.
will be repeated before substantial time
elapses. It is also unlikely that an
*At-risk BMI may be lower in some ethnic groups. individual will develop signicant
complications of diabetes within 3 years
of a negative test result. In the modeling
signicant public health burdens. There lower event rates than predicted. The of a control unscreened arm limits the ability to
is often a long presymptomatic phase absence denitely prove that screening impacts
before the diagnosis of type 2 diabetes is outcomes. Mathematical modeling studies
made. Simple tests to detect preclinical suggest that screening, independent of risk
disease are readily available. The factors, beginning at age 30 or 45 years is highly
duration of glycemic burden is a strong cost-effective (,$11,000 per quality-adjusted
predictor of adverse outcomes, and life-year gained) (19).
effective interventions exist to prevent
BMI Cut Points
progression of prediabetes to diabetes
Testing recommendations for diabetes in
(see Section IV) and to reduce risk of
asymptomatic, undiagnosed adults are listed in
complications of diabetes (see Section
Table 4. Testing should be considered in adults
VI).
of any age with BMI
Type 2 diabetes is frequently not $25 kg/m2 and one or more of the
diagnosed until complications appear. known risk factors for diabetes. In addition to
Approximately one-fourth of the U.S. the listed risk factors, certain medications, such
population may have undiagnosed as glucocorticoids and antipsychotics (20), are
diabetes. Mass screening of known to increase the risk of type 2 diabetes.
asymptomatic individuals has not There is compelling evidence that lower BMI cut
effectively identied those with points suggest diabetes risk in some racial and
prediabetes or diabetes, and rigorous ethnic groups. In a large multiethnic cohort
clinical trials to provide such proof are study, for an equivalent incidence rate of
unlikely to occur. In a large randomized diabetes conferred by a BMI of 30 kg/m in
2

controlled trial (RCT) in Europe, general non- Hispanic whites, the BMI cutoff value was
practice patients between the ages of 40 24 kg/m2 in South Asians, 25 kg/m2 in Chinese,
69 years were screened for diabetes, then and 26 kg/m2 in African Americans (21).
randomized by practice to routine Disparities in screening rates, not explainable
diabetes care or intensive treatment of by insurance status, are highlighted by evidence
multiple risk factors. After 5.3 years of that despite much higher prevalence of type 2
follow-up, CVD risk factors were diabetes, ethnic minorities in an insured
modestly but signicantly improved with population are no more likely than non- Hispanic
intensive treatment. Incidence of rst whites to be screened for diabetes (22). Because
CVD event and mortality rates were not age is a major risk factor for diabetes, in those
signicantly different between groups without these
(18). This study would seem to add
support for early treatment of screen-
detected diabetes, as risk factor control
was excellent even in the routine
treatment arm and both groups had
study, repeat screening every 3 or
5 years was cost-effective (19).
Community Screening
Testing should be carried out
within the health care setting
because of the need for follow-up
and discussion of abnormal
results. Community screening
outside a health care setting is not
recommended because people
with positive tests may not seek,
or have access to, appropriate
follow-up testing and care.
Conversely, there may be failure
to ensure appropriate repeat
testing for individuals who test
negative. Community screening
may also be poorly targeted; i.e.,
it may fail to reach the groups
most at risk and inappropriately
test those at low risk or even
those already diagnosed.
B. Screening for Type 2 Diabetes in
Children
Recommendation
c Testing to detect type 2
diabetes and prediabetes
should be considered in
children and adolescents who
are overweight and who have
two or more additional risk
factors for diabetes (Table 5). E

In the last decade, the incidence of


type 2 diabetes in adolescents has
increased dramatically, especially
in minority populations (31). As
with adult recommendations,
children and youth at increased
risk for the presence or the
development of type 2 diabetes
should be tested within the health
care setting (32).
A1C in Pediatrics and prevalence of type 1 diabetes is diabetes at the rst prenatal visit in
Recent studies question the validity of increasing (31,37,38). Several studies
A1C in the pediatric population, suggest that measuring islet
especially in ethnic minorities, and autoantibodies in relatives of those with
suggest OGTT or FPG as more suitable type 1 diabetes may identify individuals
diagnostic tests (33). However, many of who are at risk for developing type 1
these studies do not recognize that diabetes. Such testing, coupled with
diabetes diagnostic criteria are based education about diabetes symptoms and
upon long-term health outcomes, and close follow-up in an observational clinical
validations are not currently available in study, may enable earlier identication of
the pediatric population (34). ADA type 1 diabetes onset. A recent study
acknowledges the limited data reported the risk of progression to type 1
supporting A1C for diagnosing diabetes diabetes from the time of seroconversion
in children and adolescents. However, to autoantibody positivity in three
aside from rare instances, such as cystic pediatric cohorts from Finland, Germany,
brosis and hemoglobinopathies, ADA and the U.S. Of the 585 children who
continues to recommend A1C in this developed more than two autoantibodies,
cohort (35,36). The modied nearly 70% developed type
recommendations of the ADA consensus 1 diabetes within 10 years and 84%
statement Type 2 within
Diabetes in Children and Adolescents 15 years (39,40). These ndings are
are summarized in Table 5. highly signicant because, while the
German group was recruited from
C. Screening for Type 1 Diabetes offspring of parents with type 1 diabetes,
Recommendation the Finnish and Colorado groups were
c Inform type 1 diabetic patients of the recruited from the general population.
opportunity to have their relatives Remarkably, the ndings in all three
screened for type 1 diabetes risk in groups were the same, suggesting that
the setting of a clinical research the same sequence of events led to
study. E clinical disease in both sporadic and
genetic cases of type 1 diabetes. There is
Type 1 diabetic patients often present
evidence to suggest that early diagnosis
with acute symptoms of diabetes and
may limit acute complications (39) and
markedly elevated blood glucose levels,
extend long-term endogenous insulin
and some cases are diagnosed with life- production (41). While there is currently
threatening ketoacidosis. The incidence a lack of accepted screening programs,
one should consider referring relatives of
Table 5Testing for type 2 diabetes those with type 1 diabetes for antibody
in asymptomatic children* testing for risk assessment in the setting
Criteria
of a clinical research study (http://www2.
c Overweight (BMI .85th percentile
for age and sex, weight for height . diabetestrialnet.org).
85th percentile, or weight .120% of Widespread clinical testing of
ideal for height) asymptomatic low-risk individuals is not
Plus any two of the following risk factors: currently recommended. Higher-risk
c Family history of type 2 diabetes in
individuals may be screened, but only in
rst- or second-degree relative
the context of a clinical research setting.
c Race/ethnicity (Native American,
African American, Latino, Asian Individuals who screen positive will be
American, Pacic Islander) counseled about the risk of developing
c Signs of insulin resistance or diabetes, diabetes symptoms, and the
conditions associated with insulin prevention of DKA. Numerous clinical
resistance (acanthosis nigricans, studies are being conducted to test
hypertension, dyslipidemia,
various methods of preventing type 1
polycystic ovarian syndrome, or
small-for-gestational-age birth weight)
diabetes in those with evidence of
c Maternal history of diabetes or GDM autoimmunity (www.clinicaltrials.gov).
during the childs gestation
Age of initiation: age 10 years or at onset III. DETECTION AND DIAGNOSIS OF
of puberty, if puberty occurs at GESTATIONAL DIABETES MELLITUS
a younger age
Recommendations
Frequency: every 3 years
c Screen for undiagnosed type 2
*Persons aged 18 years and younger.
those with risk factors, using standard
diagnostic criteria. B
c Screen for GDM at 2428 weeks of
gestation in pregnant women not
previously known to have diabetes. A
c Screen women with GDM for persistent
diabetes at 612 weeks postpartum,
using the OGTT and
nonpregnancy diagnostic criteria. E
c Women with a history of GDM should have
lifelong screening for the development of
diabetes or
prediabetes at least every 3 years. B
c Women with a history of GDM found to
have prediabetes should receive lifestyle
interventions or metformin to prevent
diabetes. A
c Further research is needed to establish
a uniform approach to diagnosing
GDM. E

For many years, GDM was dened as any


degree of glucose intolerance with onset or
rst recognition during
pregnancy (13), whether or not the condition
persisted after pregnancy, and not excluding
the possibility that unrecognized glucose
intolerance may
have antedated or begun concomitantly with
the pregnancy. This denition facilitated a
uniform strategy for detection and
classication of GDM, but its limitations were
recognized for many years. As the ongoing
epidemic of obesity and diabetes has led to
more type 2 diabetes in women of
childbearing age, the number of pregnant
women with undiagnosed type 2 diabetes has
increased (42). Because of this, it is
reasonable to screen women with risk factors
for type
2 diabetes (Table 4) at their initial prenatal
visit, using standard diagnostic criteria (Table
2). Women with diabetes in the rst trimester
should receive a diagnosis of overt, not
gestational,
diabetes.
GDM carries risks for the mother and
neonate. Not all adverse outcomes are of
equal clinical importance. The Hyperglycemia
and Adverse Pregnancy Outcome (HAPO)
study (43), a large- scale (;25,000 pregnant
women) multinational epidemiological study,
demonstrated that risk of adverse
maternal, fetal, and neonatal
outcomes continuously increased as a
function of maternal glycemia at 2428
weeks, even within ranges previously
Table 6Screening for and diagnosis of GDM
considered normal for pregnancy. For One-step (IADPSG consensus)
most complications, there was no Perform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 h, at
threshold for risk. These results have 2428 weeks of gestation in women not previously diagnosed with overt diabetes.
led to careful reconsideration of the The OGTT should be performed in the morning after an overnight fast of at least 8 h.
diagnostic criteria for GDM. GDM The diagnosis of GDM is made when any of the following plasma glucose values are
screening can be accomplished with exceeded:
c Fasting: $92 mg/dL (5.1 mmol/L)
either of two strategies: c 1 h: $180 mg/dL (10.0 mmol/L)
c 2 h: $153 mg/dL (8.5 mmol/L)
1. One-step 2-h 75-g OGTT or
Two-step (NIH consensus)
2. Two-step approach with a 1-h
Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h (Step 1), at
50-g (nonfasting) screen followed 2428 weeks of gestation in women not previously diagnosed with overt diabetes.
by a 3-h 100-g OGTT for those who If the plasma glucose level measured 1 h after the load is $140 mg/dL* (7.8 mmol/L), proceed
screen positive (Table 6) to
100-g OGTT (Step 2). The 100-g OGTT should be performed when the patient is fasting.
Different diagnostic criteria will identify The diagnosis of GDM is made when at least two of the following four plasma glucose levels
different magnitudes of maternal (measured fasting, 1 h, 2 h, 3 h after the OGTT) are met or exceeded:
hyperglycemia and maternal/fetal risk. Ca rp ent er/ Co us ta n or NDDG

In the 2011 Standards of Care (44), ADA cFasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L)
for the rst time recommended that all c1h 180 mg/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L)
c2h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L)
pregnant women not known to have
c 3 h 140 mg/ dL (7 .8 mm ol /L ) 14 5 mg /dL (8 .
prior diabetes undergo a 75-g OGTT at
2428 weeks of gestation based on an 0 mmo l/ L)
International Association of Diabetes NDDG, National Diabetes Data Group. *The American College of Obstetricians and
and Pregnancy Study Groups (IADPSG) Gynecologists (ACOG) recommends a lower threshold of 135 mg/dL (7.5 mmol/L) in high-risk
ethnic minorities with higher prevalence of GDM; some experts also recommend 130 mg/dL
consensus meeting (45). Diagnostic cut (7.2 mmol/L).
points for the fasting, 1-h, and 2-h PG hyperglycemia than identied using continuation of the two-step
measurements were dened that older GDM diagnostic criteria and that
conveyed an odds ratio for adverse found modest benets including
outcomes of at least 1.75 compared reduced rates of large-for-gestational-
with women with the mean glucose age (LGA) births (46,47). However, while
levels in the HAPO study, a strategy treatment of lower threshold
anticipated to signicantly increase the hyperglycemia can reduce LGA, it has
prevalence of GDM (from 56% to not been shown to reduce primary
;1520%), primarily because only one cesarean delivery rates. Data are lacking
abnormal value, not two, is sufcient to on how treatment of lower threshold
make the diagnosis. ADA recognized hyperglycemia impacts prognosis of
that the anticipated increase in the future diabetes for the mother and
incidence of GDM diagnosed by these future obesity, diabetes risk, or other
criteria would have signicant impact metabolic consequences for the
on the costs, medical infrastructure offspring. The frequency of follow-up
capacity, and potential for increased and blood glucose monitoring for these
medicalization of pregnancies women has also not yet been
previously categorized as normal, but standardized, but is likely to be less
recommended these diagnostic criteria intensive than for women diagnosed by
changes in the context of worrisome the older criteria.
worldwide increases in obesity and
National Institutes of Health
diabetes rates with the intent of
Consensus Report
optimizing gestational outcomes for
Since this initial IADPSG
women and their babies. It is important recommendation, the National
to note that 8090% of women in both
Institutes of Health (NIH) completed a
of the mild GDM studies (whose glucose consensus development conference
values overlapped with the thresholds
involving a 15-member panel with
recommended herein) could be representatives from obstetrics/
managed with lifestyle therapy alone.
gynecology, maternal-fetal medicine,
The expected benets to these pediatrics, diabetes research,
pregnancies and offspring are inferred
biostatistics, and other related elds
from intervention trials that focused on
(48). Reviewing the same available data,
women with lower levels of
the NIH consensus panel recommended
approach of screening with a 1-h
50-g glucose load test (GLT)
followed by a 3-h
100-g OGTT for those who screen
positive, a strategy commonly
used in the U.S. Key factors
reported in the NIH panels
decision-making process were the
lack of clinical trial interventions
demonstrating the benets of the
one- step strategy and the
potential
negative consequences of
identifying a large new group of
women with GDM. Moreover,
screening with a 50-g GLT does
not require fasting and is
therefore easier to accomplish for
many women. Treatment of
higher threshold maternal
hyperglycemia, as identied by
the two- step approach, reduces
rates of neonatal macrosomia,
LGA, and shoulder dystocia,
without increasing small-for-
gestational- age births (49).
How do two different groups of
experts arrive at different GDM
screening and
diagnosis recommendations?
Because glycemic dysregulation
exists on a
continuum, the decision to pick a
single binary threshold for
diagnosis requires
balancing the harms and benets
associated with greater versus
lesser sensitivity. While data from
the HAPO study demonstrated a
correlation between increased
fasting glucose levels identied
through the one-step
strategy with increased odds for adverse
S2020 Position Diabetes Care Volume 37, Supplement 1, January 2014
Statement

pregnancy outcomes, this large patterns. Adjusting for BMI moderately, lifestyle interventions as delivered
observational study was not designed but not completely, attenuated this
to determine the benet of association (52).
intervention. Moreover, there are no
available cost-effective analyses to IV. PREVENTION/DELAY OF TYPE 2
examine the balance of achieved DIABETES
benets versus the increased costs Recommendations
generated by this strategy. c Patients with IGT A, IFG E, or an A1C
The conicting recommendations from 5.76.4% E should be referred to an
these two consensus panels underscore effective ongoing support program
several key points: targeting weight loss of 7% of body
weight and increasing physical
1. There are insufcient data to activity to at least 150 min/week of
strongly demonstrate the superiority moderate activity such as walking.
of one strategy over the other. c Follow-up counseling appears to be
2. The decision of which strategy to important for success. B
implement must therefore be made c Based on the cost-effectiveness of
based on the relative values placed diabetes prevention, such programs
on currently unmeasured factors should be covered by third-party
(e.g., cost-benet estimation, payers. B
willingness to change practice based c Metformin therapy for prevention
on correlation studies rather than of type 2 diabetes may be
clinical intervention trial results, considered
relative role of cost considerations, in those with IGT A, IFG E, or an
and available infrastructure). A1C 5.76.4% E, especially for those
3. Further research is needed to resolve with BMI .35 kg/m2, aged
these uncertainties. ,60 years, and women with prior
GDM. A
There remains strong consensus that c At least annual monitoring for the
establishing a uniform approach to development of diabetes in those
diagnosing GDM will have extensive with prediabetes is suggested. E
benets for patients, caregivers, and c Screening for and treatment of
policymakers. Longer-term outcome modiable risk factors for CVD is
studies are currently underway. suggested. B
Because some cases of GDM may RCTs have shown that individuals at high
represent preexisting undiagnosed type risk for developing type 2 diabetes (IFG,
2 diabetes, women with a history of IGT, or both) can signicantly decrease
GDM should be screened for diabetes the rate of diabetes onset with
612 weeks postpartum, using particular interventions (2329). These
nonpregnant OGTT criteria. Because of include intensive lifestyle modication
their antepartum treatment for programs that have been shown to be
hyperglycemia, A1C for diagnosis of very effective (;58% reduction after
persistent diabetes at the postpartum 3 years) and pharmacological agents
visit is not recommended (50). Women metformin, a-glucosidase inhibitors,
with a history of GDM have a greatly orlistat, and thiazolidinediones, each of
increased subsequent diabetes risk (51) which has been shown to decrease
and should be followed up with incident diabetes to various degrees.
subsequent screening for the Follow-up of all three large studies of
development of diabetes or lifestyle intervention has shown
prediabetes, as outlined in Section II. sustained reduction in the rate of
Lifestyle interventions or metformin conversion to type 2 diabetes, with
should be offered to women with a 43% reduction at 20 years in the Da
history of GDM who develop Qing study (53), 43% reduction at 7
prediabetes, as discussed in Section IV. years in the Finnish Diabetes
In the prospective Nurses Health Study Prevention Study (DPS) (54), and 34%
II, subsequent diabetes risk after a reduction at 10 years in the U.S.
history of GDM was signicantly lower Diabetes Prevention Program Outcomes
in women who followed healthy eating Study (DPPOS) (55). A cost-
effectiveness model suggested that
care.diabetesjournals.org Position Statement
in the DPP are cost-effective (56), and actual S2121
cost data from the DPP and DPPOS conrm
that lifestyle interventions are highly cost-
effective (57). Group delivery of the DPP
intervention in community settings has the
potential to be signicantly less expensive
while still achieving similar weight loss (58).
The Centers for Disease Control and
Prevention (CDC) helps coordinate the National
Diabetes Prevention Program, a resource
designed to bring evidence-based lifestyle
change programs for preventing type 2
diabetes to communities (http://www.cdc.gov/
diabetes/prevention/index.htm).
Given the clinical trial results and the known
risks of progression of prediabetes to
diabetes, persons with an A1C of 5.76.4%,
IGT, or IFG should be counseled on lifestyle
changes with goals similar to those of the
DPP (7% weight loss and moderate physical
activity of at least 150 min/week). Metformin
has a strong evidence base and demonstrated
long-term safety as pharmacological therapy
for diabetes prevention (59). For other drugs,
cost, side effects, and lack of a persistent
effect require consideration (60).

Metformin
Metformin was less effective than lifestyle
modication in the DPP and DPPOS, but may
be cost-saving over a
10-year period (57). It was as effective as
lifestyle modication in participants with a
BMI $35 kg/m2, but not signicantly better
than placebo in those over age 60 years (23).
In the DPP, for women with a history of
GDM, metformin and intensive lifestyle
modication led to an equivalent 50%
reduction in diabetes risk (61). Metformin
therefore might reasonably be recommended
for very-high-risk individuals (e.g., history of
GDM, very obese, and/or those with more
severe
or progressive hyperglycemia).
People with prediabetes often have other
cardiovascular risk factors, such as obesity,
hypertension, and
dyslipidemia, and are at increased risk for
CVD events. While treatment goals are the
same as for other patients
without diabetes, increased vigilance is
warranted to identify and treat these and
other risk factors (e.g., smoking).
V. DIABETES CARE enable the health care team to The management plan should be
A. Initial Evaluation optimally manage the patient with formulated as a collaborative
A complete medical evaluation should diabetes. therapeutic alliance among the patient
be performed to classify the diabetes, and family, the physician, and other
detect the presence of diabetes B. Management members of the health care team. A
complications, review previous People with diabetes should receive variety of strategies and techniques
treatment and risk factor control in medical care from a team that may should be used to provide adequate
patients with established diabetes, include physicians, nurse practitioners, education and development of
assist in formulating a management physicians assistants, nurses, dietitians, problem-solving skills in the numerous
plan, and provide a basis for pharmacists, and mental health aspects of diabetes management.
continuing care. Laboratory tests professionals with expertise in diabetes. Treatment goals and plans should be
appropriate to the evaluation of each In this collaborative and integrated individualized and take patient
patients team approach, the individuals with preferences into account. The
medical condition should be diabetes must also assume an active management plan should recognize
completed. A focus on the components role in their care. diabetes self-management education
of comprehensive care (Table 7) will (DSME) and ongoing diabetes support as
integral components of care. In
developing the plan, consideration
Table 7Components of the comprehensive diabetes evaluation
Medical history
should be given to the patients age,
c Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory nding) school or work schedule and conditions,
c Eating patterns, physical activity habits, nutritional status, and weight history; growth and physical activity, eating patterns, social
development in children and adolescents situation and cultural factors, presence
c Diabetes education history of diabetes complications, health
c Review of previous treatment regimens and response to therapy (A1C records) priorities, and other medical conditions.
c Current treatment of diabetes, including medications, medication adherence and barriers
thereto, meal plan, physical activity patterns, and readiness for behavior change C. Glycemic Control
c Results of glucose monitoring and patients use of data 1. Assessment of Glycemic Control
c DKA frequency, severity, and cause
Two primary techniques are available
c Hypoglycemic episodes
c Hypoglycemia awareness
for health providers and patients to
c Any severe hypoglycemia: frequency and cause assess the effectiveness of the
c History of diabetes-related complications management plan on glycemic control:
c Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of patient self-monitoring of blood glucose
foot lesions; autonomic, including sexual dysfunction and gastroparesis) (SMBG) or interstitial glucose, and A1C.
c Macrovascular: CHD, cerebrovascular disease, and PAD
c Other: psychosocial problems,* dental disease*
a. Glucose Monitoring
Recommendations
Physical examination
c Height, weight, BMI c Patients on multiple-dose insulin
c Blood pressure determination, including orthostatic measurements when indicated (MDI) or insulin pump therapy should
c Fundoscopic examination* do SMBG prior to meals and snacks,
c Thyroid palpation occasionally postprandially, at
c Skin examination (for acanthosis nigricans and insulin injection sites)
bedtime, prior to exercise, when they
c Comprehensive foot examination
suspect low blood glucose, after
c Inspection
c Palpation of dorsalis pedis and posterior tibial pulses
treating low blood glucose until they
c Presence/absence of patellar and Achilles reexes are normoglycemic, and prior to
c Determination of proprioception, vibration, and monolament sensation critical tasks such as driving. B
Laboratory evaluation c When prescribed as part of a broader
c A1C, if results not available within past 23 months educational context, SMBG results
c If not performed/available within past year may be helpful to guide treatment
c Fasting lipid prole, including total, LDL, and HDL cholesterol and triglycerides decisions and/or patient self-
c Liver function tests
management for patients using less
c Test for urine albumin excretion with spot urine albumin-to-creatinine ratio
c Serum creatinine and calculated GFR
frequent insulin injections or
c TSH in type 1 diabetes, dyslipidemia, or women over age 50 years noninsulin therapies. E
Referrals c When prescribing SMBG, ensure that
c Eye care professional for annual dilated eye exam patients receive ongoing instruction
c Family planning for women of reproductive age and regular evaluation of SMBG
c Registered dietitian for MNT technique and SMBG results, as well
c DSME as their ability to use SMBG data to
c Dentist for comprehensive periodontal examination
adjust therapy. E
c Mental health professional, if needed
c When used properly, continuous
*See appropriate referrals for these categories. glucose monitoring (CGM) in
conjunction with intensive insulin complications (63). For patients on randomized trial
regimens is a useful tool to lower nonintensive insulin regimens, such as
A1C in selected adults (aged $25 those with type 2 diabetes on basal
years) with type 1 diabetes. A insulin, when to prescribe SMBG and the
c Although the evidence for A1C testing frequency are unclear because
lowering is less strong in children, there is insufcient evidence for testing
teens, and younger adults, CGM may in this cohort.
be helpful in these groups. Success
Several randomized trials have called
correlates with adherence to ongoing
into question the clinical utility and
use of the device. C
c CGM may be a supplemental tool to cost- effectiveness of routine SMBG in
SMBG in those with hypoglycemia noninsulin-treated patients (6466).
unawareness and/or frequent A recent meta-analysis suggested that
hypoglycemic episodes. E SMBG reduced A1C by 0.25% at
6 months (67), but a Cochrane review
Major clinical trials of insulin-treated concluded that the overall effect of
patients that demonstrated the benets SMBG in such patients is minimal up to
of intensive glycemic control on 6 months after initiation and subsides
diabetes complications have included after 12 months (68). A key
SMBG as part of multifactorial consideration is that SMBG alone does
interventions, suggesting that SMBG is a not lower blood glucose level; to be
component of effective therapy. SMBG useful, the information must be
allows patients to evaluate their integrated into clinical and self-
individual response to therapy and management plans.
assess whether glycemic targets are
SMBG accuracy is instrument and user
being achieved. Results of SMBG can be
dependent (69), so it is important to
useful in preventing hypoglycemia and
evaluate each patients monitoring
adjusting medications (particularly
technique, both initially and at regular
prandial insulin doses), medical
intervals thereafter. Optimal use of
nutrition therapy (MNT), and physical
SMBG requires proper review and
activity. Evidence also supports a
interpretation of the data, both by the
correlation between SMBG frequency
patient and provider. Among patients
and lower A1C (62).
who checked their blood glucose at
SMBG frequency and timing should be least once daily, many reported taking
dictated by the patients specic needs no action when results were high or
and goals. SMBG is especially important low (70). In one study of insulin-nave
for patients treated with insulin to patients with suboptimal initial
monitor for and prevent asymptomatic glycemic control, use of structured
hypoglycemia and hyperglycemia. Most SMBG (a paper tool to collect and
patients with type 1 diabetes or on interpret
intensive insulin regimens (MDI or 7-point SMBG proles over 3 days at
insulin pump therapy) should consider least quarterly) reduced A1C by 0.3%
SMBG prior to meals and snacks, more than an active control group (71).
occasionally postprandially, at bedtime, Patients should be taught how to use
prior to exercise, when they suspect low SMBG data to adjust food intake,
blood glucose, after treating low blood exercise, or pharmacological therapy to
glucose until they are normoglycemic, achieve specic goals. The ongoing need
and prior to critical tasks such as for and frequency of SMBG should be
driving. For many patients, this will reevaluated at each routine visit.
require testing 68 times daily,
although Continuous Glucose Monitoring Real-
individual needs may vary. A database time CGM through the measurement of
study of almost 27,000 children and interstitial glucose (which correlates
adolescents with type 1 diabetes well with plasma glucose) is available.
showed that, after adjustment for These sensors require calibration with
multiple confounders, increased daily SMBG, and the latter are still required
frequency of SMBG was signicantly for making acute treatment decisions.
associated with lower A1C (20.2% per CGM devices have alarms for hypo- and
additional test per day, leveling off at
hyperglycemic excursions. A 26-week
ve tests per day) and with fewer acute
of 322 type 1 diabetic patients showed that
adults aged $25 years using intensive insulin
therapy and CGM experienced a 0.5%
reduction in A1C (from ;7.6 to 7.1%)
compared with usual intensive insulin therapy
with SMBG (72). Sensor use in those ,25
years of age (children, teens, and adults) did
not result in signicant A1C lowering, and there
was no signicant difference in hypoglycemia
in any group. The greatest predictor of A1C
lowering for all age-groups was frequency of
sensor use, which was lower in younger age-
groups. In a smaller RCT of
129 adults and children with baseline A1C
,7.0%, outcomes combining A1C and
hypoglycemia favored the group using CGM,
suggesting that CGM is also benecial for
individuals with type 1 diabetes who have
already achieved excellent control (72).
Overall, meta-analyses suggest that
compared with SMBG, CGM use is
associated with A1C lowering by
;0.26% (73). The technology may be
particularly useful in those with
hypoglycemia unawareness and/or frequent
hypoglycemic episodes,
although studies have not shown signicant
reductions in severe hypoglycemia (73). A
CGM device equipped with an automatic low
glucose suspend feature was recently
approved by the U.S. Food and Drug
Administration (FDA). The ASPIRE trial of 247
patients showed that sensor- augmented
insulin pump therapy with a low glucose
suspend signicantly
reduced nocturnal hypoglycemia,
without increasing A1C levels for those over
16 years of age (74). These devices may offer
the opportunity to reduce severe
hypoglycemia for those with a
history of nocturnal hypoglycemia. CGM forms
the underpinning for the articial pancreas
or the closed-loop system. However, before
CGM is widely adopted, data must be reported
and analyzed using a standard universal
template that is predictable and intuitive (75).
b. A1C
Recommendations
c Perform the A1C test at least two times a
year in patients who are meeting
treatment goals (and who have stable
glycemic control). E
c Perform the A1C test quarterly in
patients whose therapy has changed
or who are not meeting glycemic different recommendations about testing A1C or
Table 8Correlation of A1C with
goals. E average glucose
c Use of POC testing for A1C provides Mean plasma glucose
the opportunity for more timely
treatment changes. E A1 C (%) mg/ dL mm ol/ L
6 126 7.0
A1C reects average glycemia over 7 154 8.6
several months (69) and has strong 8 183 10.2
predictive value for diabetes 9 212 11.8
complications (76,77). Thus, A1C testing 10 240 13.4
should be performed routinely in all 11 269 14.9
patients with diabetes: at initial 12 298 16 .5
assessment and as part of continuing
These estimates are based on ADAG data of
care. Measurement approximately ;2,700 glucose measurements over 3
every 3 months determines whether a months per A1C measurement in 507 adults
patients glycemic targets have been with type 1, type 2, and no diabetes. The
reached and maintained. The frequency correlation between A1C and average
glucose was 0.92 (ref. 78). A calculator for
of A1C testing should be dependent on converting A1C results into eAG, in either
the clinical situation, the treatment mg/dL or mmol/L, is available at http://
regimen used, and the clinicians professional.diabetes.org/ eAG.
judgment. Some patients with stable
glycemia well within target may do well
with testing only twice per year. Chemistry have determined that the
Unstable or highly intensively managed correlation (r 5 0.92) is strong enough
patients (e.g., pregnant type 1 diabetic to justify reporting both the A1C result
women) may require testing more and an estimated average glucose (eAG)
frequently than every 3 months. result when a clinician orders the A1C
test. The table in pre-2009 versions of
A1C Limitations
the Standards of Medical Care in
As mentioned above, the A1C test is
Diabetes describing the correlation
subject to certain limitations.
between A1C and mean glucose was
Conditions that affect erythrocyte
derived from relatively sparse data (one
turnover (hemolysis, blood loss) and
7-point prole over 1 day per A1C
hemoglobin variants must be
reading) in the primarily non-Hispanic
considered, particularly when the A1C
white type 1 diabetic participants in the
result does not correlate with the
DCCT (79). Clinicians should note that
patients clinical situation (69). A1C also
the numbers in the table are now
does not provide a measure of
different because they are based on ;
glycemic variability or hypoglycemia.
2,800 readings per A1C in the ADAG
For patients prone to glycemic
trial.
variability, especially type 1 diabetic
patients or type 2 diabetic patients In the ADAG study, there were no
with severe insulin deciency, glycemic signicant differences among racial and
control is best evaluated by the ethnic groups in the regression lines
combination of results from self- between A1C and mean glucose,
monitoring and the A1C. The A1C may although there was a trend toward a
also conrm the accuracy of the difference between the African/African
patients meter (or the patients American and non-Hispanic white
reported SMBG results) and the cohorts. A small study comparing A1C to
adequacy of the SMBG testing schedule. CGM data in type 1 diabetic children
found a highly statistically signicant
A1C and Plasma Glucose correlation between A1C and mean
Table 8 contains the correlation blood glucose, although the correlation
between A1C levels and mean plasma (r 5
glucose levels based on data from the 0.7) was signicantly lower than in the
international A1C-Derived Average ADAG trial (80). Whether there are
Glucose (ADAG) trial using frequent signicant differences in how A1C
SMBG and CGM in 507 adults (83% non- relates to average glucose in children or
Hispanic whites) with type 1, type 2, in African American patients is an area
and no diabetes (78). The ADA and the for further study (33,81). For the time
American Association for Clinical being, the question has not led to
to different interpretations of the Complications Hyperglycemia
clinical meaning of given levels of denes diabetes, and glycemic
A1C in those populations. control is fundamental to
For patients in whom A1C/eAG diabetes management. The
and measured blood glucose DCCT study (76), a prospective
appear discrepant, clinicians RCT of intensive versus
should consider the possibilities standard glycemic control in
of hemoglobinopathy or patients with relatively recently
altered red cell turnover, and the diagnosed type 1 diabetes showed
options of more frequent and/or denitively that improved glycemic
different timing
of SMBG or use of CGM. Other
measures of chronic glycemia such
as fructosamine are available, but
their linkage to average glucose
and their prognostic signicance
are not as clear as for A1C.
2. Glycemic Goals in Adults
Recommendations
c Lowering A1C to below or
around 7% has been shown to
reduce microvascular
complications of diabetes and,
if implemented soon after the
diagnosis of diabetes, is
associated with long-term
reduction in macrovascular
disease.
Therefore, a reasonable A1C
goal for many nonpregnant
adults is ,7%. B
c Providers might reasonably
suggest more stringent A1C
goals (such as
,6.5%) for selected individual
patients, if this can be achieved
without signicant
hypoglycemia or other
adverse effects of treatment.
Appropriate patients might
include
those with short duration of
diabetes, long life expectancy,
and no signicant CVD. C
c Less stringent A1C goals (such
as ,8%) may be appropriate for
patients with a history of severe
hypoglycemia, limited life
expectancy, advanced
microvascular or macrovascular
complications, and extensive
comorbid conditions and in
those with long- standing
diabetes in whom the general
goal is difcult to attain despite
DSME, appropriate glucose
monitoring, and effective doses
of multiple glucose- lowering
agents including insulin. B
Diabetes Control and
Complications
Trial/Epidemiology of Diabetes
Interventions and
control is associated with signicantly when setting glycemic targets. three trials were conducted in participants
decreased rates of microvascular However, based on physician judgment with more long-standing diabetes (mean
(retinopathy and nephropathy) and and patient preferences, select patients, duration 811 years) and
neuropathic complications. Follow-up especially those with little comorbidity
of the DCCT cohorts in the Epidemiology and long life expectancy, may benet
of Diabetes Interventions and from adopting more intensive glycemic
Complications (EDIC) study (82,83) targets (e.g., A1C target ,6.5%) as long
demonstrated persistence of these as signicant hypoglycemia does not
microvascular benets in previously become a barrier.
intensively treated subjects, even
though their glycemic control Cardiovascular Disease Outcomes
approximated that of previous standard CVD is a more common cause of death
arm subjects during follow-up. than microvascular complications in
populations with diabetes. However, it
Kumamoto and UK Prospective is less clearly impacted by hyperglycemia
Diabetes Study levels or intensity of glycemic control. In
The Kumamoto (84) and UK Prospective the DCCT, there was a trend toward
Diabetes Study (UKPDS) (85,86) lower risk of CVD events with intensive
conrmed that intensive glycemic control. In the 9-year post-DCCT follow-
control was associated with signicantly up of the EDIC cohort, participants
decreased rates of microvascular and previously randomized to the intensive
neuropathic complications in type 2 arm had a signicant 57% reduction in
diabetic patients. Long-term follow-up the risk of nonfatal myocardial infarction
of the UKPDS cohorts showed enduring (MI),
effects of early glycemic control on stroke, or CVD death compared with
most microvascular complications (87). those previously in the standard arm
Three landmark trials (ACCORD, (92). The benet of intensive glycemic
ADVANCE, and VADT, described in control in this type 1 diabetic cohort has
further detail below) were designed to recently been shown to persist for
examine the impact of intensive A1C several decades (93).
control on CVD outcomes and showed In type 2 diabetes, there is evidence that
that lower A1C levels were associated more intensive treatment of glycemia in
with reduced onset or progression of newly diagnosed patients may reduce
microvascular complications (8890). long- term CVD rates. During the UKPDS
Epidemiological analyses of the DCCT trial, there was a 16% reduction in CVD
and UKPDS (76,77) demonstrate a events (combined fatal or nonfatal MI and
curvilinear relationship between sudden death) in the intensive glycemic
A1C and microvascular complications. control arm that did not reach statistical
Such analyses suggest that, on a signicance (P 5 0.052), and there was
population level, the greatest number of no suggestion of benet on other CVD
complications will be averted by taking outcomes (e.g., stroke). However, after
patients from very poor control to fair/ 10 years of follow-up, those originally
good control. These analyses also randomized to intensive glycemic control
suggest that further lowering of A1C had signicant long-term reductions in MI
from 7 to 6% is associated with further (15% with sulfonylurea or insulin as
reduction in the risk of microvascular initial pharmacotherapy, 33% with
complications, though the absolute risk metformin as initial pharmacotherapy)
reductions become much smaller. Given and in all-cause mortality (13% and 27%,
the substantially increased risk of respectively) (87).
hypoglycemia in type 1 diabetes trials, The Action to Control Cardiovascular
and now seen in recent type 2 diabetes Risk in Diabetes (ACCORD), Action in
trials, the risks of lower glycemic targets Diabetes and Vascular Disease: Preterax
may outweigh the potential benets on and Diamicron Modied Release
microvascular complications on a Controlled Evaluation (ADVANCE), and
population level. The concerning the Veterans Affairs Diabetes Trial
mortality ndings in the ACCORD trial (VADT) studies suggested no signicant
(91) and the relatively much greater reduction in CVD outcomes with
effort required to achieve near- intensive glycemic control in participants
euglycemia should also be considered who had more advanced type 2
diabetes than UKPDS participants. All
either known CVD or multiple cardiovascular
risk factors. Details of these studies are
reviewed extensively in an ADA position
statement (94).
ACCORD
The ACCORD study participants had either
known CVD or two or more major
cardiovascular risk factors and were
randomized to intensive glycemic control
(goal A1C ,6%) or standard glycemic control
(goal A1C 78%). The glycemic control
comparison was halted early due to an
increased mortality rate in the intensive
compared with the standard arm (1.41 vs.
1.14%/year; hazard ratio [HR] 1.22 [95% CI
1.01
1.46]); with a similar increase in
cardiovascular deaths. Initial analysis of the
ACCORD data (evaluating variables including
weight gain, use of any specic drug or drug
combination, and hypoglycemia) did not
identify a clear explanation for the excess
mortality in the intensive arm (91). A
subsequent analysis showed no increase in
mortality in the intensive arm participants
who achieved A1C levels below 7%, nor in
those who lowered their A1C quickly after
trial enrollment. There was no A1C level at
which intensive versus standard arm
participants had signicantly
lower mortality. The highest risk for mortality
was observed in intensive arm participants
with the highest A1C levels (95). Severe
hypoglycemia was signicantly more likely in
participants randomized to the intensive
glycemic control arm. Unlike the DCCT, where
lower achieved A1C levels were related to
signicantly increased rates of severe
hypoglycemia, in ACCORD every 1%
decline in A1C from baseline to 4 months into
the trial was associated with a signicant
decrease in the rate of severe hypoglycemia in
both arms (95).
ADVANCE
The primary outcome of ADVANCE was a
combination of microvascular events
(nephropathy and retinopathy) and major
adverse cardiovascular events (MI, stroke, and
cardiovascular death). Intensive glycemic
control (A1C ,6.5%, vs. treatment to local
standards) signicantly reduced the primary
end point, primarily due to a signicant
reduction in the microvascular
outcome, specically development of
albuminuria (.300 mg/24 h), with
no signicant reduction in the advanced atherosclerosis, and advanced associated with increased cardiovascular
macrovascular outcome. There was no age/frailty may benet from less risk independent of FPG in some
difference in overall or cardiovascular aggressive targets. Providers should be epidemiological studies. In diabetic
mortality between the two arms (89). vigilant in preventing severe subjects, surrogate measures of vascular
VADT hypoglycemia in patients with advanced pathology, such as endothelial
The primary outcome of the VADT was a disease and should not aggressively dysfunction, are negatively affected by
composite of CVD events. The trial attempt to achieve near-normal A1C postprandial hyperglycemia (101). It is
randomized type 2 diabetic participants levels in patients in whom such targets clear that postprandial hyperglycemia,
who were uncontrolled on insulin or on cannot be safely and reasonably like preprandial hyperglycemia,
maximal dose oral agents (median entry achieved. Severe or frequent contributes to elevated A1C levels, with
A1C 9.4%) to a strategy of intensive hypoglycemia is an absolute indication its relative contribution being greater at
glycemic control (goal A1C ,6.0%) or for the modication of treatment A1C levels that are closer to 7%.
standard glycemic control, with a regimens, including setting higher However, outcome studies have clearly
planned A1C separation of at least glycemic goals. Many factors, including shown
1.5%. The cumulative primary outcome patient preferences, should be taken A1C to be the primary predictor of
was nonsignicantly lower in the into account when developing a complications, and landmark glycemic
intensive arm (88). An ancillary study of patients individualized goals (99) (Fig. control trials such as the DCCT and
the VADT demonstrated that intensive 1). UKPDS relied overwhelmingly on
glycemic control signicantly reduced preprandial SMBG. Additionally, an RCT
the primary CVD outcome in individuals Glycemic Goals in patients with known CVD found no
with less atherosclerosis at baseline but Recommended glycemic goals for many CVD benet of insulin regimens
not in persons with more extensive nonpregnant adults are shown in targeting postprandial glucose compared
baseline atherosclerosis (96). A post hoc Table 9. The recommendations are with those targeting preprandial glucose
analysis showed that mortality in the based on those for A1C values, with (102). A reasonable recommendation
intensive versus standard glycemic blood glucose levels that appear to for postprandial testing and targets is
control arm was related to duration of correlate with achievement of an A1C of that for individuals who have premeal
diabetes at study enrollment. Those ,7%. The issue of pre- versus glucose values within
with diabetes duration less than 15 postprandial SMBG targets is complex target but have A1C values above
years had a mortality benet in the (100). Elevated postchallenge (2-h target, monitoring postprandial plasma
intensive arm, while those with OGTT) glucose values have been glucose (PPG) 12 h after the start of the
duration of 20 years or more had higher meal and treatment aimed at reducing
mortality in the intensive arm (97).
The evidence for a cardiovascular
benet of intensive glycemic control
primarily rests on long-term follow-up
of study cohorts treated early in the
course of type 1 and type 2 diabetes,
and a subset analyses of ACCORD,
ADVANCE, and VADT. A group-level
meta-analysis of the latter three trials
suggests that glucose lowering has a
modest (9%) but statistically signicant
reduction in major CVD outcomes,
primarily nonfatal MI, with no
signicant effect on mortality.
However, heterogeneity of the
mortality effects across studies was
noted. A prespecied subgroup analysis
suggested that major CVD outcome
reduction occurred in patients without
known CVD at baseline (HR 0.84 [95%
CI 0.740.94]) (98). Conversely, the
mortality ndings in
ACCORD and subgroup analyses of the Figure 1Approach to management of hyperglycemia. Depiction of the elements of decision
VADT suggest that the potential risks of making used to determine appropriate efforts to achieve glycemic targets. Characteristics/
intensive glycemic control may predicaments toward the left justify more stringent efforts to lower A1C, whereas those toward
the right are compatible with less stringent efforts. Where possible, such decisions should be
outweigh its benets in some patients. made in conjunction with the patient, reecting his or her preferences, needs, and values. This
Those with long duration of diabetes, scale is not designed to be applied rigidly but to be used as a broad construct to help guide
known history of severe hypoglycemia, clinical decisions. Adapted with permission from Ismail-Beigi et al. (99).
Table 9Summary of glycemic recommendations for many nonpregnant 1. Use MDI injections (34 injections
adults with diabetes per day of basal and prandial insulin)
A1C ,7.0%* or CSII therapy.
Preprandial capillary plasma glucose 70130 mg/dL* (3.97.2 mmol/L) 2. Match prandial insulin to
Peak postprandial capillary plasma glucose ,180 mg/dL* (,10.0 mmol/L) carbohydrate intake, premeal
c *Goals should be individualized based on: blood glucose, and anticipated
c duration of diabetes activity.
c age/life expectancy 3. For most patients (especially
c comorbid conditions
with hypoglycemia), use insulin
c known CVD or advanced microvascular
complications analogs.
c hypoglycemia unawareness 4. For patients with frequent
c individual patient considerations nocturnal hypoglycemia and/or
c More or less stringent glycemic goals hypoglycemia unawareness, use of
may be appropriate for individual patients sensor-augmented low glucose
c Postprandial glucose may be targeted if A1C
suspend threshold pump may be
goals are not met despite reaching
considered.
preprandial glucose goals
Postprandial glucose measurements should be made 12 h after the beginning of the meal,
generally peak levels in patients with diabetes. There are excellent reviews to guide
the initiation and management of
insulin therapy to achieve desired
PPG values to ,180 mg/dL may help (three to four injections per day of components:
lower A1C. basal and prandial insulin) or
Glycemic goals for children are provided continuous subcutaneous insulin
in Section VIII.A.1.a. infusion (CSII). A
c Most people with type 1 diabetes
Glycemic Goals in Pregnant Women should be educated in how to match
The goals for glycemic control for prandial insulin dose to carbohydrate
women with GDM are based on intake, premeal blood glucose, and
recommendations from the Fifth anticipated activity. E
International Workshop-Conference on c Most people with type 1 diabetes
Gestational Diabetes Mellitus (103) and should use insulin analogs to reduce
have the following targets for maternal hypoglycemia risk. A
capillary glucose concentrations:
Screening
c Preprandial: #95 mg/dL (5.3 c Consider screening those with type 1
mmol/L), and either: diabetes for other autoimmune
c 1-h postmeal: #140 mg/dL diseases (thyroid, vitamin B12
(7.8 mmol/L) or deciency, celiac) as appropriate. B
c 2-h postmeal: #120 mg/dL
(6.7 mmol/L) The DCCT clearly showed that intensive
insulin therapy (three or more injections
For women with preexisting type 1 or per day of insulin, or CSII (or insulin
type 2 diabetes who become pregnant, pump therapy) was a key part of
the following are recommended as improved glycemia and better
optimal glycemic goals, if they can be outcomes (76,92). The study was carried
achieved without excessive out with short- and intermediate-acting
hypoglycemia (104): human insulins. Despite better
microvascular outcomes, intensive
c Premeal, bedtime, and overnight insulin therapy was associated with a
glucose 6099 mg/dL (3.35.4 high rate of severe hypoglycemia (62
mmol/L) episodes per 100 patient-years of
c Peak postprandial glucose 100129 therapy). Since the DCCT, a number of
mg/dL (5.47.1 mmol/L) rapid-acting and long-acting insulin
c A1C ,6.0% analogs have been developed. These
analogs are associated with less
D. Pharmacological and Overall hypoglycemia with equal A1C lowering
Approaches to Treatment in type 1 diabetes (105,106).
1. Insulin Therapy for Type 1 Diabetes
Recommended therapy for type 1
c Most people with type 1 diabetes diabetes consists of the following
should be treated with MDI injections
glycemic goals (105,107,108). Although most
studies of MDI versus pump
therapy have been small and of short
duration, a systematic review and
meta-analysis concluded that there
were no systematic differences in A1C
or severe hypoglycemia rates in
children and adults between the two
forms of intensive insulin therapy (73).
Recently, a large randomized trial in
type 1 diabetic patients with nocturnal
hypoglycemia reported that sensor-
augmented insulin pump therapy with the
threshold-suspend feature reduced nocturnal
hypoglycemia, without
increasing glycated hemoglobin values
(74). Overall, intensive management
through pump therapy/CGM and active
patient/family participation should be
strongly encouraged (109111). For
selected individuals who have
mastered carbohydrate counting,
education on the impact of protein and fat on
glycemic excursions can be
incorporated into diabetes
management (112).

Screening
Because of the increased frequency of other
autoimmune diseases in type 1
diabetes, screening for thyroid dysfunction,
vitamin B12 deciency, and celiac disease
should be considered based on signs and
symptoms. Periodic screening in asymptomatic
individuals
has been recommended, but the effectiveness
and optimal frequency are unclear.
Figure 2Antihyperglycemic therapy in type 2 diabetes: general recommendations. DPP-4-i, DPP-4 inhibitor; Fxs, bone fractures; GI, gastrointestinal;
GLP-1- RA, GLP-1 receptor agonist; HF, heart failure; SU, sulfonylurea; TZD, thiazolidinedione. For further details, see ref. 113. Adapted with
permission.

2. Pharmacological Therapy for patient preferences, cost and potential side


Considerations include efcacy, cost,
Hyperglycemia in Type 2 Diabetes effects of each class, effects
potential side effects, effects on
Recommendations
weight, comorbidities, hypoglycemia
c Metformin, if not contraindicated risk, and patient preferences. E
and if tolerated, is the preferred c Due to the progressive nature of type
initial pharmacological agent for type 2 diabetes, insulin therapy is
2 diabetes. A eventually indicated for many
c In newly diagnosed type 2 diabetic patients with type 2 diabetes. B
patients with markedly symptomatic
and/or elevated blood glucose levels The ADA and the European Association
or A1C, consider insulin therapy, with for the Study of Diabetes (EASD) formed
or without additional agents, from a joint task force to evaluate the data
the outset. E and develop recommendations for the
c If noninsulin monotherapy at use of antihyperglycemic agents in type 2
maximum tolerated dose does not diabetic patients (113). This 2012
achieve or maintain the A1C target position statement is less prescriptive
over 3 months, add a second oral than prior algorithms and discusses
agent, a glucagon-like peptide 1 (GLP- advantages and disadvantages of the
1) receptor agonist, or insulin. A available medication classes and
c A patient-centered approach should considerations for their use. A patient-
be used to guide choice of centered approach is stressed, including
pharmacological agents.
on body weight, and hypoglycemia
risk. The position statement
reafrms metformin as the
preferred initial agent, barring
contraindication or intolerance,
either in addition to lifestyle
counseling and support for weight
loss and exercise, or when lifestyle
efforts alone have not achieved or
maintained glycemic goals.
Metformin has a long-standing
evidence base for efcacy and
safety, is inexpensive, and may
reduce risk of cardiovascular events
(87). When metformin fails to
achieve or maintain glycemic goals,
another agent should be added.
Although there are numerous
trials comparing
dual therapy to metformin
alone, few directly compare
drugs as add-on
therapy. Comparative
effectiveness meta-analyses
(114) suggest that
overall, each new class of noninsulin
agents added to initial therapy lowers
A1C around 0.91.1%.
Many patients with type 2 diabetes carbohydrate, protein, and fat for all than quantity. B
eventually require and benet from people with diabetes B; therefore,
insulin therapy. The progressive nature macronutrient distribution should be
of type 2 diabetes and its therapies based on individualized assessment
should be regularly and objectively of current eating patterns,
explained to patients. Providers should preferences, and metabolic goals. E
avoid using insulin as a threat or c A variety of eating patterns
describing it as a failure or punishment. (combinations of different foods or
Equipping patients with an algorithm food groups) are acceptable for the
for self-titration of insulin doses based management of diabetes. Personal
on SMBG results improves glycemic preference (e.g., tradition, culture,
control in type 2 diabetic patients religion, health beliefs and goals,
initiating insulin (115). Refer to the economics) and metabolic goals
ADA-EASD position statement for more should be considered when
details on pharmacotherapy for recommending one eating pattern
hyperglycemia in type 2 diabetes (113) over another. E
(Fig. 2).
Carbohydrate Amount and Quality
E. Medical Nutrition Therapy c Monitoring carbohydrate intake,
General Recommendations whether by carbohydrate counting
c Nutrition therapy is recommended or experience-based estimation,
for all people with type 1 and type 2 remains a key strategy in achieving
diabetes as an effective component glycemic control. B
of the overall treatment plan. A c For good health, carbohydrate intake
c Individuals who have prediabetes or from vegetables, fruits, whole grains,
diabetes should receive legumes, and dairy products should
individualized MNT as needed to be advised over intake from other
achieve treatment goals, preferably carbohydrate sources, especially
provided by a registered dietitian those that contain added fats, sugars,
familiar with the components of or sodium. B
diabetes MNT. A c Substituting low-glycemic load foods
c Because diabetes nutrition therapy for higher-glycemic load foods may
can result in cost savings B and modestly improve glycemic control. C
improved outcomes such as c People with diabetes should consume
reduction in A1C A, nutrition therapy at least the amount of ber and
should be adequately reimbursed by whole grains recommended for the
insurance and other payers. E general public. C
c While substituting sucrose-
Energy Balance, Overweight, and Obesity
containing foods for isocaloric
c For overweight or obese adults with amounts of other carbohydrates may
type 2 diabetes or at risk for diabetes, have similar blood glucose effects,
reducing energy intake while consumption should be minimized to
maintaining a healthful eating avoid displacing nutrient-dense food
pattern is recommended to promote choices. A
weight loss. A c People with diabetes and those at
c Modest weight loss may provide risk for diabetes should limit or
clinical benets (improved glycemia, avoid intake of sugar-sweetened
blood pressure, and/or lipids) in some beverages (from any caloric
individuals with diabetes, especially sweetener including high-fructose
those early in the disease process. To corn syrup and sucrose) to reduce
achieve modest weight loss, risk for weight gain and worsening of
intensive lifestyle interventions cardiometabolic risk
(counseling about nutrition therapy, prole. B
physical activity, and behavior
change) with ongoing support are Dietary Fat Quantity and Quality
recommended. A c Evidence is inconclusive for an ideal
Eating Patterns and Macronutrient
amount of total fat intake for people
Distribution
with diabetes; therefore, goals should
be individualized. C Fat quality
c Evidence suggests that there is not an
appears to be far more important
ideal percentage of calories from
c In people with type 2 diabetes, a
Mediterranean-style, MUFA-rich
eating pattern may benet glycemic
control and CVD risk factors and
can therefore be recommended as an
effective alternative to a lower- fat,
higher-carbohydrate eating
pattern. B
c As recommended for the general public, an
increase in foods containing long-chain n-3
fatty acids (EPA and DHA) (from fatty sh)
and n-3 linolenic acid (ALA) is
recommended for individuals with
diabetes because of their benecial
effects on lipoproteins, prevention of heart
disease, and associations with positive
health outcomes in
observational studies. B
c The amount of dietary saturated fat,
cholesterol, and trans fat
recommended for people with
diabetes is the same as that
recommended for the general
population. C

Supplements for Diabetes Management


c There is no clear evidence of benet from
vitamin or mineral
supplementation in people with
diabetes who do not have underlying
deciencies. C
c Routine supplementation with antioxidants,
such as vitamins E and C and carotene, is not
advised because of lack of evidence of
efcacy and concern related to long-term
safety. A
c Evidence does not support
recommending n-3 (EPA and DHA)
supplements for people with
diabetes for the prevention or
treatment of cardiovascular
events. A
c There is insufcient evidence to support
the routine use of micronutrients such as
chromium, magnesium, and vitamin D to
improve glycemic control in people with
diabetes. C
c There is insufcient evidence to
support the use of cinnamon or other
herbs/supplements for the treatment of
diabetes. C
c It is reasonable for individualized
meal planning to include optimization of
food choices to meet recommended daily
allowance/ dietary reference intake for all
micronutrients. E
Alcohol of calories from fat, and ;1618% from
therapy or individualized education
c If adults with diabetes choose to sessions have reported A1C decreases
drink alcohol, they should be advised of 0.31% for type 1 diabetes (117120)
to do so in moderation (one drink and 0.52% for type 2 diabetes
per day or less for adult women and (85,121137).
two drinks per day or less for adult
men). E Individuals with type 1 diabetes should
c Alcohol consumption may place be offered intensive insulin therapy
people with diabetes at increased risk education using the carbohydrate-
for delayed hypoglycemia, especially counting meal planning approach
if taking insulin or insulin (117,119,120,124,138140); this
secretagogues. Education and approach has been shown to improve
awareness regarding the recognition glycemic control (139,141). Consistent
and management of delayed carbohydrate intake with respect to
hypoglycemia is warranted. C time and amount can result in improved
glycemic control for individuals using
Sodium
xed daily insulin doses (142,143). A
c The recommendation for the general simple diabetes meal planning approach
population to reduce sodium to such as portion control or healthful
,2,300 mg/day is also appropriate food choices may be better suited for
for people with diabetes. B individuals with health literacy and
c For individuals with both diabetes
numeracy concerns (125127).
and hypertension, further reduction
in sodium intake should be Weight loss of 28 kg may provide
individualized. B clinical benets in those with type 2
diabetes, especially early in the disease
Primary Prevention of Type 2 Diabetes
process (144146). Weight loss studies
c Among individuals at high risk for have used a variety of energy-restricted
developing type 2 diabetes, eating patterns, with no clear evidence
structured programs that emphasize that one eating pattern or optimal
lifestyle changes that include macronutrient distribution was ideal.
moderate weight loss (7% of body
Although several studies resulted in
weight) and regular physical activity
improvements in A1C at 1 year
(150 min/week), with dietary
(144,145,147149), not all weight loss
strategies including reduced calories
interventions led to 1-year A1C
and reduced intake of dietary fat, can
improvements (128,150154). The most
reduce the risk for developing
consistently identied changes in
diabetes and are therefore
cardiovascular risk factors were an
recommended. A
increase in HDL cholesterol (144,145,
c Individuals at high risk for type 2
147,149,153,155), decrease in
diabetes should be encouraged to
triglycerides
achieve the U.S. Department of
(144,145,149,155,156) and
Agriculture (USDA) recommendation
decrease in blood pressure
for dietary ber (14 g ber/1,000
kcal) and foods containing whole (144,145,147,151,153,155).
grains (one-half of grain intake). B Intensive lifestyle programs with
frequent follow-up are required to
The ADA recently released an updated achieve signicant reductions in excess
position statement on nutrition therapy body weight and improve clinical
for adults living with diabetes (116). indicators (145,146). Several studies
Nutrition therapy is an integral have attempted to identify the optimal
component of diabetes prevention, mix of macronutrients for meal plans of
management, and self-management people with diabetes. However, a recent
education. All individuals with diabetes systematic review (157) found that
should receive individualized MNT there was no ideal macronutrient
preferably provided by a registered distribution and that macronutrient
dietitian who is knowledgeable and proportions should be individualized.
skilled in providing diabetes MNT. Studies show that people with diabetes
Comprehensive group diabetes on average eat about 45% of their
education programs including nutrition calories from carbohydrate, ;3640%
protein (158160). A variety of increased obesity and CHD with
eating patterns have been shown high intake of fat (166). The
to be effective in managing type of fatty acids consumed is
diabetes, including more important than total
Mediterranean-style amount of fat when looking at
(144,146,169), Dietary metabolic goals and risk of CVD
Approaches to Stop Hypertension (146,167,168).
(DASH)-style (161), plant-based Multiple RCTs including
(vegan or vegetarian) (129), patients with type 2 diabetes
lower-fat (145), and have reported improved
lower-carbohydrate patterns
(144,163).
Studies examining the ideal
amount of carbohydrate intake
for people with
diabetes are inconclusive,
although monitoring carbohydrate
intake and considering the
available insulin are key strategies
for improving postprandial
glucose control
(117,142,143,158). The literature
concerning glycemic index and
glycemic load in individuals with
diabetes is complex, although
reductions in A1C of 20.2% to
20.5% have been demonstrated
in some studies. In many
studies, it is often
difcult to discern the
independent effect of ber
compared with that of glycemic
index on glycemic control and
other outcomes. Improvements
in CVD risk measures are mixed
(164). Recent studies have shown
modest effect of ber on
lowering preprandial glucose and
mixed results on improving CVD
risk factors. A systematic review
(157) found consumption of
whole grains was not associated
with improvements in glycemic
control in people with type 2
diabetes, although it may reduce
systemic inammation. One study
did nd a potential benet of
whole grain intake in reducing
mortality and CVD (165).
Limited research exists
concerning the ideal amount of
fat for individuals with diabetes.
The Institute of Medicine has
dened an acceptable
macronutrient distribution range
(AMDR) for all adults for total fat
of 2035% of energy with no
tolerable upper intake level
dened. This AMDR was based on
evidence for CHD risk with a low
intake of fat and high intake of
carbohydrate, and evidence for
S3030 Position Diabetes Care Volume 37, Supplement 1, January 2014
Statement

glycemic control and/or blood lipids 2 diabetes (204) have warranted caution team to improve clinical outcomes,
when a Mediterranean-style, MUFA- for universal sodium restriction to 1,500 health status, and quality of life in a
rich eating pattern was consumed mg in this population. For individuals cost-effective manner (206).
(144,146,151,169171). Some of these with diabetes and hypertension, setting a DSME and DSMS are essential elements
studies also included caloric restriction, sodium intake goal of ,2,300 mg/day of diabetes care (207209), and the
which may have contributed to should be considered only on an current National Standards for Diabetes
improvements in glycemic control or individual basis. Goal sodium intake Self- Management Education and Support
blood lipids (169,170). The ideal ratio of recommendations should take into (206) are based on evidence for their
n-6 to n-3 fatty acids has not been account palatability, availability, additional benets. Education helps people with
determined; however, PUFA and MUFA cost of specialty low sodium products, diabetes initiate effective self-
are recommended substitutes for and the difculty of achieving both low management and cope with diabetes
saturated or trans fat (167,172). sodium recommendations and a when they are rst diagnosed. Ongoing
A recent systematic review (157) nutritionally adequate diet (205). For
DSME and DSMS also help people with
concluded that supplementation with complete discussion and references of all
diabetes maintain effective self-
n-3 fatty acids did not improve recommendations, see Nutrition Therapy
management throughout a lifetime of
glycemic control but that higher dose Recommendations for the Management
diabetes as they face new challenges and
supplementation decreased of Adults With Diabetes (116).
treatment advances become available.
triglycerides in individuals with type 2 DSME enables patients (including youth)
F. Diabetes Self-Management
diabetes. Six short-duration RCTs to optimize metabolic control, prevent
Education and Support
comparing n-3 supplements to placebo and manage complications, and maximize
Recommendations
published since the systematic review quality of life, in a cost-effective manner
reported minimal or no benecial c People with diabetes should receive
(208,210).
effects (173,174) or mixed/ DSME and diabetes self-management
support (DSMS) according to National Current best practice of DSME is a skills-
inconsistent benecial effects
Standards for Diabetes Self- based approach that focuses on helping
(175177) on CVD risk factors and
Management Education and Support those with diabetes make informed self-
other health issues. Three longer-
when their diabetes is diagnosed and management choices (206,208). DSME
duration studies also reported mixed
as needed thereafter. B has changed from a didactic approach
outcomes (178180). Thus, RCTs do focusing on providing information
c Effective self-management and
not support recommending n-3 to more theoretically based
quality of life are the key outcomes
supplements for primary or secondary empowerment models that focus on
of DSME and DSMS and should be
prevention of CVD. Little evidence has helping those with diabetes make
measured and monitored as part of
been published about the relationship informed self-management decisions
care. C
between dietary intake of saturated (208). Diabetes care has shifted to an
c DSME and DSMS should address
fatty acids and dietary cholesterol and approach that is more patient centered
psychosocial issues, since emotional
glycemic control and CVD risk in people and places the person with diabetes and
well-being is associated with positive
with diabetes. Therefore, people with his or her family at the center of the
diabetes outcomes. C
diabetes should follow the guidelines care model working in collaboration
c DSME and DSMS programs are
for the general population for the with health care professionals. Patient-
appropriate venues for people with
recommended intakes of saturated fat, centered care is respectful of and
prediabetes to receive education and
dietary cholesterol, and trans fat (167). responsive to individual patient
support to develop and maintain
Published data on the effects of plant behaviors that can prevent or delay preferences, needs, and values and
stanols and sterols on CVD risk in the onset of diabetes. C ensures that patient values guide all
individuals with diabetes include four c Because DSME and DSMS can result decision making (211).
RCTs that reported benecial effects for in cost-savings and improved
total, LDL, and non-HDL cholesterol outcomes B, DSME and DSMS should Evidence for the Benets of Diabetes
(181184). be adequately reimbursed by third- Self-Management Education and
There is limited evidence that the use of party payers. E Support
Multiple studies have found that DSME
vitamin, mineral, or herbal supplements
DSME and DSMS are the ongoing is associated with improved diabetes
is necessary in the management of
processes of facilitating the knowledge, knowledge and improved self-care
diabetes (185201).
skill, and ability necessary for diabetes behavior (206,207), improved clinical
Limited studies have been published on self-care. This process incorporates the outcomes such as lower A1C (209,212
sodium reduction in people with needs, goals, and life experiences of the 216), lower self-reported weight (207),
diabetes. A recent Cochrane review person with diabetes. The overall improved quality of life (213,216,217),
found that decreasing sodium intake objectives of DSME and DSMS are to healthy coping (218,219), and lower
reduces blood pressure in those with support informed decision making, self- costs (220,221). Better outcomes were
diabetes (202). However, two other care behaviors, problem solving, and reported for DSME interventions that
studies in type 1 diabetes (203) and active collaboration with the health care were longer and included follow-up
type support (DSMS) (207,222224), that
were culturally (225,226) and age maintaining behaviors that can prevent Reimbursement for Diabetes Self-
appropriate (227,228) and were tailored or delay the onset of diabetes Management Education and Support DSME,
to individual needs and preferences, (206,244,245). when provided by a program that meets
and that addressed psychosocial issues national standards for DSME and is recognized
and incorporated behavioral strategies by ADA or other approval
(207,208,218,219,229231). Both bodies, is reimbursed as part of the
individual and group approaches have Medicare program as overseen by the
been found effective (232,233). There is Centers for Medicare and Medicaid
growing evidence for the role of a Services (CMS). DSME is also covered by
community health workers (234) and most health insurance plans.
peer (235239) and lay leaders (240) in Although DSMS has been shown to be
delivering DSME and DSMS as part of instrumental for improving outcomes, as
the DSME/S team (241). described in Evidence for the
Diabetes education is associated with Benets of Diabetes Self-Management
increased use of primary and preventive Education and Support, and can be
services (220,242,243) and lower use of provided in formats such as phone calls and
acute, inpatient hospital services (220). via telehealth, it currently has
Patients who participate in diabetes limited reimbursement as face-to-face visits
education are more likely to follow best included as follow-up to DSME.
practice treatment recommendations,
particularly among the Medicare G. Physical Activity
population, and have lower Medicare Recommendations
and commercial claim costs (221,242). c As is the case for all children, children with
diabetes or prediabetes should be
The National Standards for Diabetes encouraged to engage in at least
Self-Management Education and 60 min of physical activity each day. B
Support c Adults with diabetes should be advised to
The National Standards for Diabetes perform at least 150 min/week of moderate-
Self-Management Education and intensity aerobic physical activity (5070% of
Support are designed to dene quality maximum heart rate), spread over at least 3
DSME and DSMS and to assist diabetes days/week with no more than 2 consecutive
educators days without exercise. A
in a variety of settings to provide c In the absence of contraindications, adults
evidence-based education and self- with type 2 diabetes should be encouraged to
management support (206). The perform resistance training at least twice per
standards are reviewed and updated
week. A
every 5 years by a task force
representing key organizations involved Exercise is an important part of the diabetes
in the eld of diabetes education and management plan. Regular exercise has been
care. shown to improve blood glucose control,
reduce cardiovascular risk factors, contribute to
Diabetes Self-Management Education
weight loss, and improve well-being.
and Support Providers and People
Furthermore, regular exercise may prevent type
With Prediabetes
2 diabetes in high-risk individuals (2325).
The standards for DSME and DSMS also
Structured exercise interventions of at least 8
apply to the education and support of
weeks
people with prediabetes. Currently,
duration have been shown to lower A1C by an
there are signicant barriers to the
average of 0.66% in people with type 2
provision of education and support to
diabetes, even with no signicant change in
those with prediabetes. However, the
BMI (246). There are
strategies for supporting successful
considerable data for the health
behavior change and the healthy
benets (e.g., increased cardiovascular tness,
behaviors recommended for people with
muscle strength, improved insulin sensitivity,
prediabetes are largely identical to those
etc.) of regular physical activity for those with
for people with diabetes. As barriers to
type 1 diabetes (247). Higher levels of exercise
care are overcome, providers of DSME
intensity are associated with greater
and DSMS, given their training and
experience, are particularly well
equipped to assist people with
prediabetes in developing and
improvements in A1C and in type 2 diabetes (255,256). In
tness (248). Other benets the absence of
include slowing the decline in contraindications, patients with
mobility among type 2
overweight patients with diabetes should be encouraged
diabetes (249). A joint position to do at least two weekly
statement of ADA and the sessions of resistance exercise
American College of Sports (exercise with free weights or
Medicine summarizes the weight machines), with each
evidence for the benets of session consisting of at least
exercise in people with type 2 one set of ve or
diabetes (250).

Frequency and Type of Exercise


The U.S. Department of Health
and Human Services Physical
Activity Guidelines for Americans
(251) suggest that adults over age
18 years do 150 min/week of
moderate-intensity, or 75
min/week of vigorous aerobic
physical activity, or an equivalent
combination of the two. In
addition, the guidelines suggest
that adults also do muscle-
strengthening activities that
involve all major muscle groups 2
or more days/ week. The
guidelines suggest that adults
over age 65 years, or those with
disabilities, follow the adult
guidelines if possible or (if this is
not possible) be as physically
active as they are able. Studies
included in the meta-analysis of
effects of exercise interventions
on
glycemic control (246) had a mean
of 3.4 sessions/week, with a
mean of 49 min/ session. The
DPP lifestyle intervention, which
included 150 min/week of
moderate-intensity exercise, had
a
benecial effect on glycemia in
those with prediabetes.
Therefore, it seems reasonable
to recommend that people with
diabetes follow the physical
activity guidelines for the
general population.
Progressive resistance exercise
improves insulin sensitivity in
older men with type 2 diabetes to
the same or even a greater extent
as aerobic exercise (252). Clinical
trials have provided strong
evidence for the A1C lowering
value of resistance training in
older adults with type 2 diabetes
(253,254), and for an additive
benet of combined aerobic and
resistance exercise in adults with
more different resistance exercises hypoglycemia are usually Exercise in the Presence of Specic
involving the large muscle groups (250). advised in these cases. Long-Term Complications of Diabetes
Pre-exercise Evaluation of the Retinopathy. In the presence of
Diabetic Patient proliferative diabetic retinopathy
As discussed more fully in Section (PDR) or severe non-PDR (NPDR),
VI.A.5, the area of screening vigorous aerobic or resistance
asymptomatic diabetic patients for exercise may be contraindicated
coronary artery disease (CAD) remains because of the risk of triggering
unclear. An ADA consensus statement vitreous hemorrhage or retinal
on this issue detachment (259).
concluded that routine screening is not
Peripheral Neuropathy. Decreased pain
recommended (257). Providers should
sensation and a higher pain threshold in
use clinical judgment in this area.
the extremities result in increased risk of
Certainly, high-risk patients should be
skin breakdown and infection and of
encouraged to start with short periods
Charcot joint destruction with some
of low-intensity exercise and increase
forms of exercise. However, studies have
the intensity and duration slowly.
shown that moderate-intensity walking
Providers should assess patients for
may not lead to increased risk of foot
conditions that might contraindicate
ulcers or reulceration in those with
certain types of exercise or predispose
peripheral neuropathy (260). In
to injury, such as uncontrolled
addition, 150 min/week of moderate
hypertension, severe autonomic
exercise was reported to improve
neuropathy, severe peripheral
outcomes in patients with milder forms
neuropathy or history of foot lesions,
of neuropathy (260a). All individuals
and unstable proliferative retinopathy.
with peripheral neuropathy should wear
The patients age and previous
proper footwear and examine their feet
physical activity level should be
daily to detect lesions early. Anyone
considered. For type 1 diabetic
with a foot injury or open sore should be
patients, the provider
restricted to nonweight-bearing
should customize the exercise regimen
activities.
to the individuals needs. Those with
complications may require a more Autonomic Neuropathy. Autonomic
thorough evaluation (247). neuropathy can increase the risk of
exercise-induced injury or adverse
Exercise in the Presence of
event through decreased cardiac
Nonoptimal Glycemic Control
responsiveness to exercise, postural
Hyperglycemia. When people with type 1 hypotension, impaired thermoregulation,
diabetes are deprived of insulin for impaired night vision due to impaired
1248 h and are ketotic, exercise can papillary reaction, and higher
worsen hyperglycemia and ketosis susceptibility to hypoglycemia (454).
(258); therefore, vigorous activity Cardiovascular autonomic neuropathy
should be avoided in the presence of (CAN) is also an independent risk
ketosis. However, it is not necessary to factor for cardiovascular death and
postpone exercise based simply on silent myocardial ischemia (261).
hyperglycemia, provided the patient Therefore, individuals with diabetic
feels well and urine and/or blood autonomic neuropathy should
ketones are negative. undergo cardiac investigation before
Hypoglycemia. In individuals taking beginning physical activity more
insulin and/or insulin secretagogues, intense than that to which they are
physical activity can cause accustomed.
hypoglycemia if medication dose or Albuminuria and Nephropathy. Physical
carbohydrate consumption is not activity can acutely increase urinary
altered. For individuals on these protein excretion. However, there is no
therapies, added carbohydrate should evidence that vigorous exercise increases
be ingested if pre- exercise glucose the rate of progression of diabetic kidney
levels are ,100 mg/dL (5.6 mmol/L). disease and likely no need for any specic
Hypoglycemia is less common in exercise restrictions for people with
diabetic individuals who are not treated diabetic
with insulin or insulin secretagogues, kidney disease (262).
and no preventive measures for
H. Psychosocial Assessment and Care
Recommendations
c It is reasonable to include assessment of the
patients psychological and social situation as
an ongoing part of the medical management
of diabetes. B
c Psychosocial screening and follow-up may
include, but are not limited to, attitudes
about the illness, expectations for medical
management and outcomes, affect/ mood,
general and diabetes-related quality of life,
resources (nancial, social, and emotional),
and psychiatric history. E
c Routinely screen for psychosocial
problems such as depression and
diabetes-related distress, anxiety, eating
disorders, and cognitive impairment. B
Emotional well-being is an important part of
diabetes care and self-management.
Psychological and social problems can impair
the individuals (263265) or familys ability
(266) to carry out diabetes care tasks and
therefore compromise health status. There are
opportunities for the clinician to routinely
assess psychosocial status in a timely and
efcient manner so that referral for
appropriate services can be accomplished. A
systematic review and meta-analysis showed
that psychosocial interventions modestly but
signicantly improved A1C (standardized mean
difference 20.29%) and mental health
outcomes. However, there was a limited
association between the effects on A1C and
mental health, and no intervention
characteristics predicted benet on both
outcomes (267).
Screening
Key opportunities for routine screening of
psychosocial status occur at diagnosis, during
regularly scheduled management visits, during
hospitalizations, with the discovery of
complications, or when problems with glucose
control, quality of life, or self-management are
identied. Patients are likely to exhibit
psychological vulnerability at diagnosis and
when their medical status changes, e.g., end of
the honeymoon period, when the need for
intensied treatment is evident, and when
complications are discovered. Depression
affects about 2025% of people with diabetes
(268) and increases the risk for MI and post-MI
(269) and
all-cause mortality (270). There diabetes and depression (286,287), interventions to enhance self- management
appears to be a bidirectional and and address severe distress have demonstrated
relationship with both diabetes (271) efcacy in diabetes-related distress (219).
and metabolic syndrome (272) and
depression. I. When Treatment Goals Are Not Met
Diabetes-related distress is distinct from Some people with diabetes and their
clinical depression and is very common health care providers may not achieve the
(273276) among people with diabetes desired treatment goals (Table 9). Rethinking
and their family members (266). the treatment regimen may require assessment
Prevalence is reported as 1845%, with of barriers including income, health literacy,
an incidence of 3848% over 18 months. diabetes- related distress, depression, and
High levels of distress are signicantly competing demands, including those related to
linked to A1C, self-efcacy, dietary and family responsibilities and dynamics. Other
exercise behaviors (219,274), and strategies may include culturally appropriate
medication taking (277). Other issues and enhanced DSME and DSMS, comanagement
known to impact self-management and with a diabetes team, referral to a medical
health outcomes include but are not social worker for assistance with insurance
limited to attitudes about the illness, coverage, assessing medication-taking
expectations for medical management behaviors, or change in pharmacological
and outcomes, anxiety, general and therapy. Initiation of or increase in SMBG, use
diabetes-related quality of life, of CGM,
resources (nancial, social, and frequent contact with the patient, or referral to
emotional) (278) and psychiatric history a mental health professional or physician with
(279,280). Screening tools are available special expertise in diabetes may be useful.
for a number of these areas
J. Intercurrent Illness
(229,281,282).
The stress of illness, trauma, and/or surgery
frequently aggravates glycemic control and
Referral to Mental Health Specialist may precipitate DKA or
Indications for referral to a mental nonketotic hyperosmolar state, life- threatening
health specialist familiar with diabetes conditions that require immediate medical care
management may include gross to prevent complications and death. Any
disregard for the medical regimen (by condition leading to deterioration in glycemic
self or others) (283), depression, control necessitates more frequent monitoring
possibility of self-harm, debilitating of blood glucose and (in ketosis-prone patients)
anxiety (alone or with depression), urine or blood ketones. If accompanied by
indications of an eating disorder (284), ketosis, vomiting, or alteration in level of
or cognitive functioning that consciousness, marked hyperglycemia requires
signicantly impairs judgment. It is temporary adjustment of the treatment
preferable to incorporate regimen and immediate interaction with the
psychological assessment and diabetes care team. The patient treated with
treatment into routine care rather than noninsulin therapies or MNT alone may
waiting for a specic problem or temporarily require insulin. Adequate uid and
deterioration in metabolic or caloric intake must be assured. Infection or
psychological status (229,273). In the dehydration is more likely to necessitate
recent DAWN2 study, signicant hospitalization of the person with diabetes than
diabetes-related distress was reported the person without diabetes.
by 44.6% of the participants, but only
The hospitalized patient should be treated by a
23.7% reported that their health care
physician with expertise in diabetes
team asked them how diabetes
management. For further information on
impacted their life (273).
management of patients
Although the clinician may not feel
qualied to treat psychological
problems (285), using the patient-
provider relationship as a foundation
can increase the likelihood that the
patient will accept referral for other
services. Collaborative care
interventions and use of a team
approach have demonstrated efcacy in
with hyperglycemia in the with increased vigilance for
hospital, see Section IX.A. For hypoglycemia by the
further information on clinician, patient, and
management of DKA or caregivers if low cognition
hyperglycemic nonketotic and/or declining
hyperosmolar state, refer to the cognition is found. B
ADA statement on hyperglycemic
crises (288). Hypoglycemia is the leading
limiting factor in the glycemic
K. Hypoglycemia management of type 1 and
Recommendations insulin-treated type 2 diabetes
c Individuals at risk for (289). Mild hypoglycemia may
hypoglycemia should be asked be inconvenient or frightening
about symptomatic and to patients with diabetes.
asymptomatic hypoglycemia Severe
at
each encounter. C
c Glucose (1520 g) is the
preferred treatment for the
conscious individual with
hypoglycemia,
although any form of
carbohydrate that contains
glucose may be used. After 15
min of treatment, if SMBG
shows continued
hypoglycemia, the treatment
should be repeated. Once
SMBG returns to normal, the
individual should consume a
meal or snack to prevent
recurrence of
hypoglycemia. E
c Glucagon should be
prescribed for all individuals
at signicant risk of
severe hypoglycemia, and
caregivers or family members
of these
individuals should be
instructed on its
administration. Glucagon
administration is not
limited to health care
professionals. E
c Hypoglycemia unawareness or
one or more episodes of severe
hypoglycemia should trigger re-
evaluation of the treatment
regimen. E
c Insulin-treated patients with
hypoglycemia unawareness
or an episode of severe
hypoglycemia should be
advised to raise their
glycemic targets to strictly
avoid further hypoglycemia
for at least several weeks, to
partially reverse
hypoglycemia unawareness
and reduce risk of future
episodes. A
c Ongoing assessment of
cognitive function is suggested
hypoglycemia can cause acute harm to Hypoglycemia treatment requires patients (296). Hence, patients with one
the person with diabetes or others, ingestion of glucose- or carbohydrate- or more episodes of severe
especially if it causes falls, motor vehicle containing foods. The acute glycemic hypoglycemia may benet from at least
accidents, or other injury. A large cohort response correlates better with the short-term relaxation of glycemic
study suggested that among older glucose content than with the targets.
adults with type 2 diabetes, a history of carbohydrate content of the food. Pure L. Bariatric Surgery
severe hypoglycemia was associated glucose is the preferred treatment, but Recommendations
with greater risk of dementia (290). any form of carbohydrate that
c Bariatric surgery may be considered
contains 2
Conversely, in a substudy of the for adults with BMI .35 kg/m and
glucose will raise blood glucose.
Added
ACCORD trial, cognitive impairment at outcomes (295). fat may retard and then prolong the acute
baseline or decline in cognitive function glycemic response. Ongoing insulin activity
during the trial was signicantly or insulin secretagogues may lead to
associated with subsequent episodes of recurrent hypoglycemia unless further
severe hypoglycemia (291). Evidence food is ingested after recovery.
from the DCCT/EDIC trial, which
involved younger adults and Glucagon
adolescents with type 1 diabetes, Those in close contact with, or having
suggested no association of frequency custodial care of, people with
of severe hypoglycemia with cognitive hypoglycemia-prone diabetes (family
decline (292), as discussed in Section members, roommates, school personnel,
VIII.A.1.a. child care providers, correctional
institution staff, or coworkers) should be
As described in Section V.b.2, severe
instructed on use of glucagon kits. An
hypoglycemia was associated with
individual does not need to be a health
mortality in participants in both the
care professional to safely administer
standard and intensive glycemia arms glucagon. A glucagon kit requires a
of the ACCORD trial, but the prescription. Care should be taken to
relationships with achieved A1C and ensure that glucagon kits are not expired.
treatment intensity were not
straightforward. An association of Hypoglycemia Prevention Hypoglycemia
severe hypoglycemia with mortality prevention is a critical component of
was also found in the ADVANCE trial diabetes management. SMBG and, for
(293). An association of self-reported some patients, CGM are key tools to
severe hypoglycemia with 5-year assess therapy and detect incipient
mortality has also been reported in hypoglycemia. Patients should understand
clinical practice (294). situations that increase their risk of
hypoglycemia, such as when fasting for
In 2013, ADA and The Endocrine Society
tests or procedures, during or after
published a consensus report on the
intense exercise, and during sleep, and
impact and treatment of hypoglycemia
that hypoglycemia may increase the risk
on diabetic patients. Severe
of harm to self or others, such as with
hypoglycemia was dened as an event
driving. Teaching people with diabetes to
requiring assistance of another person.
balance insulin use, carbohydrate intake,
Young children with type 1 diabetes and
and exercise is a necessary but not
the elderly were noted as particularly
always sufcient strategy for prevention.
vulnerable due to their limited ability to
In type 1 diabetes and severely insulin-
recognize hypoglycemic symptoms and
decient type 2 diabetes, hypoglycemia
effectively communicate their needs.
unawareness, or hypoglycemia-
The report recommended that short-
associated autonomic failure, can
acting insulin sliding scales, often used in
severely compromise stringent diabetes
long-term care facilities, should be
control and quality of life. The decient
avoided and complex regimens
counter-regulatory hormone release and
simplied. Individualized patient autonomic responses in this syndrome are
education, dietary intervention (e.g., both risk factors for, and caused by,
bedtime snack to prevent overnight hypoglycemia. A corollary to this vicious
hypoglycemia), exercise management, cycle is that several weeks of avoidance
medication adjustment, glucose of hypoglycemia has been demonstrated
monitoring, and routine clinical to improve counter-regulation and
surveillance may improve patient
awareness to some extent in many type 2 diabetes, especially if diabetes
or associated comorbidities are
difcult to control with lifestyle
and pharmacological therapy. B
c Patients with type 2 diabetes
who have undergone bariatric
surgery
need lifelong lifestyle support
and medical monitoring. B
c Although small trials have shown
glycemic benet of bariatric
surgery in patients with type 2
diabetes and BMI 3035 kg/m2,
there is currently insufcient
evidence to generally recommend
surgery in patients with BMI ,35
kg/m2 outside of a research
protocol. E
c The long-term benets, cost-
effectiveness, and risks of bariatric
surgery in individuals with type 2
diabetes should be studied in well-
designed controlled trials with
optimal medical and lifestyle
therapy as the comparator. E

Bariatric and metabolic surgeries,


either gastric banding or procedures
that involve bypassing, transposing, or
resecting sections of the small
intestine, when part of a
comprehensive team approach, can be
an effective weight loss treatment for
severe obesity, and national guidelines
support its consideration for people
with type 2 diabetes who have BMI
exceeding
35 kg/m2.
Advantages
Bariatric surgery has been shown to
lead to near- or complete
normalization of glycemia in ;40
95% of patients with type 2 diabetes,
depending on the study and the
surgical procedure (297300).
A meta-analysis of bariatric
surgery studies involving 3,188
patients with diabetes reported
that 78% had
remission of diabetes (normalization
of blood glucose levels in the absence
of medications) and that the
remission rates were sustained in
studies that had follow-up exceeding
2 years (301). Remission rates tend to
be lower with procedures that only
constrict the
stomach and higher with those that surgery was not associated with decreased mortality compared with usual
bypass portions of the small intestine. care (mean follow-up 6.7 years) (309). A
Additionally, intestinal bypass study that followed patients who had
procedures may have glycemic effects undergone laparoscopic adjustable gastric
that are independent of their effects on banding (LAGB) for
weight, perhaps involving the incretin 12 years found that 60% were satised with the
axis. procedure. Nearly one out of three patients
There is also evidence for diabetes experienced band erosion, and almost half had
remission following bariatric surgery in required removal of their bands. The authors
persons with type 2 diabetes who are conclusion was that LAGB appears to result in
less severely obese. One randomized relatively poor long-term outcomes (310).
trial compared adjustable gastric Understanding the mechanisms of glycemic
banding to best available medical and improvement, long-term benets, and risks of
lifestyle therapy in subjects with type 2 bariatric surgery in individuals with type 2
diabetes and BMI 3040 kg/m2 (302). diabetes, especially those who are not severely
Overall, 73% of surgically treated obese, will require well designed clinical trials,
patients achieved remission of their with optimal medical and lifestyle therapy, and
diabetes, compared with 13% of those cardiovascular risk factors as the comparator.
treated medically. The latter group lost
only 1.7% of body weight, suggesting M. Immunization
that their therapy was not optimal. Recommendations
Overall the trial had 60 subjects, and c Annually provide an inuenza vaccine to all
only 13 had a BMI under 35 kg/m2, diabetic patients $6 months of age. C
making it difcult to generalize these c Administer pneumococcal polysaccharide
results widely to diabetic patients who vaccine to all diabetic patients $2 years of
are less severely obese or with longer age. A one-time revaccination is
duration of diabetes. In a recent recommended for individuals .65 years of
nonrandomized study of 66 people with age who
BMI 3035 kg/m2, 88% of participants have been immunized .5 years ago. Other
had remission of their type 2 diabetes indications for repeat
up to 6 years after surgery (303). vaccination include nephrotic syndrome,
chronic renal disease, and other
Disadvantages
immunocompromised states, such as after
Bariatric surgery is costly in the short
transplantation. C
term and has associated risks. Morbidity
c Administer hepatitis B vaccination to
and mortality rates directly related to
unvaccinated adults with diabetes who are
the surgery have been reduced
aged 1959 years. C
considerably in recent years, with 30-
c Consider administering hepatitis B
day mortality rates now 0.28%, similar
vaccination to unvaccinated adults with
to those of laparoscopic
diabetes who are aged $60
cholecystectomy (304). Longer-term
years. C
concerns include vitamin and mineral
deciencies, osteoporosis, and rare but
Inuenza and pneumonia are common,
often severe hypoglycemia from insulin
preventable infectious diseases associated with
hypersecretion. Cohort studies
high mortality and morbidity in the elderly and
attempting to match subjects suggest
in people with chronic diseases. Though there
that the procedure may reduce longer-
are limited studies reporting the morbidity and
term mortality rates (305).
mortality of inuenza and pneumococcal
Retrospective analyses and modeling
pneumonia specically in people with diabetes,
studies suggest that these procedures
observational studies of patients with a variety
may be cost-effective for patients with
of chronic illnesses, including diabetes, show
type 2 diabetes, when one considers
that these conditions are associated with an
reduction in subsequent health care
increase in
costs (297,306308).
Caution about the benets of bariatric
surgery is warranted. A propensity
score-adjusted analyses of older
severely obese patients with high
baseline mortality in Veterans Affairs
Medical Centers found that bariatric
hospitalizations for inuenza as lancing devices and blood
and its complications. People glucose meters, even when no
with diabetes may be at blood is visible. Blood sufcient
increased risk of the to transmit the virus has also
bacteremic form of been found in the reservoirs of
pneumococcal infection and insulin pens, resulting in
have been reported to have a warnings
high risk of nosocomial against sharing such devices
bacteremia, which has a between patients.
mortality rate as high as 50% CDC analyses suggest that,
(311). excluding persons with HBV-
Safe and effective vaccines that related risk behaviors, acute
greatly reduce the risk of serious HBV infection is about twice as
complications from these high among adults with
diseases are available (312,313).
In a case-control series, inuenza
vaccine was shown to reduce
diabetes-related hospital
admission by as much as 79%
during u epidemics (312). There
is sufcient evidence to
support that people with diabetes
have appropriate serologic and
clinical responses to these
vaccinations.
The CDC Advisory Committee on
Immunization Practices
recommends inuenza and
pneumococcal vaccines for all
individuals with diabetes (http://
www.cdc.gov/vaccines/recs/).
Hepatitis B Vaccine
Late in 2012, the Advisory
Committee on Immunization
Practices of the CDC
recommended that all
previously
unvaccinated adults with diabetes aged
1959 years be vaccinated
against hepatitis B virus
(HBV) as soon as
possible after a diagnosis of
diabetes is made. Additionally,
after assessing risk and
likelihood of an adequate
immune response, vaccinations
for those aged
60 years and over should also be
considered (314). At least 29
outbreaks of HBV in long-term
care facilities and hospitals have
been reported to the
CDC, with the majority involving
adults with diabetes receiving
assisted blood glucose
monitoring, in which such
monitoring is done by a health
care professional with
responsibility for more than
one patient. HBV is highly
transmissible and stable for
long
periods of time on surfaces such
diabetes aged 23 years and over 1. Hypertension/Blood Pressure Control monitored. E
compared with adults without diabetes. Recommendations
Seroprevalence of antibody to HBV core Screening and Diagnosis
antigen, suggesting past or current c Blood pressure should be measured
infection, is 60% higher among adults at every routine visit. Patients found
with diabetes than those without, and to have elevated blood pressure
there is some evidence that diabetes should have blood pressure
imparts a higher HBV case fatality rate. conrmed on a separate day. B
The age differentiation in the
recommendations stems from CDC Goals

economic models suggesting that c People with diabetes and


vaccination of adults with diabetes hypertension should be treated to a
who were aged 2059 years would cost systolic blood pressure (SBP) goal of
an estimated $75,000 per quality- ,140 mmHg. B
adjusted life-year saved, while cost per c Lower systolic targets, such as ,130
quality-adjusted life-year saved mmHg, may be appropriate for
increased signicantly at higher ages. certain individuals, such as younger
In addition to competing causes of patients, if it can be achieved without
mortality in older adults, the immune undue treatment burden. C
response to the vaccine declines with c Patients with diabetes should be
age (314). treated to a diastolic blood pressure
(DBP) ,80 mmHg. B
These new recommendations regarding
HBV vaccinations serve as a reminder to Treatment
clinicians that children and adults with c Patients with blood pressure .
diabetes need a number of vaccinations, 120/80 mmHg should be advised on
both those specically indicated lifestyle changes to reduce blood
because of diabetes as well as those pressure. B
recommended for the general c Patients with conrmed blood
population (http://www.cdc.gov/ pressure higher than 140/80 mmHg
vaccines/recs/). should, in addition to lifestyle
therapy, have prompt initiation and
VI. PREVENTION AND timely subsequent titration of
MANAGEMENT OF DIABETES pharmacological therapy to achieve
COMPLICATIONS blood pressure goals. B
For prevention and management of c Lifestyle therapy for elevated blood
diabetes complications in children and pressure consists of weight loss, if
adolescents, please refer to Section VIII. overweight; DASH-style dietary
Diabetes Care in Specic Populations. pattern including reducing sodium
and increasing potassium intake;
A. Cardiovascular Disease moderation of alcohol intake; and
CVD is the major cause of morbidity and increased physical activity. B
mortality for individuals with diabetes, c Pharmacological therapy for patients
and the largest contributor to the direct with diabetes and hypertension
and indirect costs of diabetes. The should comprise a regimen that
common conditions coexisting with includes either an ACE inhibitor or an
type angiotensin receptor blocker (ARB). If
2 diabetes (e.g., hypertension and one class is not tolerated, the other
dyslipidemia) are clear risk factors for should be substituted. C
CVD, and diabetes itself confers c Multiple-drug therapy (two or more
independent risk. Numerous studies agents at maximal doses) is generally
have shown the efcacy of controlling required to achieve blood pressure
individual cardiovascular risk factors in targets. B
preventing or slowing CVD in people c Administer one or more
with diabetes. Large benets are seen antihypertensive medications at
when multiple risk factors are addressed bedtime. A
globally (315,316). There is evidence c If ACE inhibitors, ARBs, or diuretics
that measures of 10-year CHD risk are used, serum creatinine/estimated
among U.S. adults with diabetes have glomerular ltration rate (eGFR) and
improved signicantly over the past serum potassium levels should be
decade (317).
c In pregnant patients with diabetes and
chronic hypertension, blood pressure
target goals of 110129/
6579 mmHg are suggested in the interest
of long-term maternal health and
minimizing impaired fetal growth. ACE
inhibitors and ARBs are contraindicated
during pregnancy. E

Hypertension is a common comorbidity of


diabetes, affecting the majority of
patients, with prevalence depending on
type of diabetes, age, obesity, and ethnicity.
Hypertension is a major risk factor for both
CVD and microvascular complications. In type
1 diabetes, hypertension is often the result
of
underlying nephropathy, while in type 2
diabetes it usually coexists with other
cardiometabolic risk factors.
Screening and Diagnosis
Blood pressure measurement should be done
by a trained individual and follow the
guidelines established for nondiabetic
individuals: measurement in the seated
position, with feet on the oor and arm
supported at heart level, after 5 min of rest.
Cuff size should be appropriate for the upper
arm circumference. Elevated values should be
conrmed on a separate day.
Home blood pressure self-monitoring and
24-h ambulatory blood pressure monitoring
may provide additional evidence of white
coat and masked hypertension and other
discrepancies between ofce and true blood
pressure. Studies in nondiabetic populations
found that home measurements may better
correlate with CVD risk than ofce
measurements (318,319). However, most of the
evidence of benets of hypertension treatment
in people with diabetes is based on ofce
measurements.
Treatment Goals
Epidemiological analyses show that blood
pressures .115/75 mmHg are associated
with increased
cardiovascular event rates and mortality in
individuals with diabetes (320322) and that
SBP .120 mmHg predict long- term end-stage
renal disease (ESRD). Randomized clinical
trials have
demonstrated the benet (reduction of CHD
events, stroke, and nephropathy) of lowering
blood pressure to ,140
mmHg systolic and ,80 mmHg
diastolic in individuals with diabetes
(320,323325). There is limited Observational data, including inappropriate for dening blood pressure
evidence for the benets of lower SBP that derived from clinical trials, targets, since sicker patients may have low
targets. may be blood pressures or, conversely, healthier or
The ACCORD trial examined whether a more adherent patients may achieve goals
lower SBP of ,120 mmHg provides more readily. A recent meta-analysis of
greater cardiovascular protection randomized trials of adults with type 2 diabetes
than an SBP level of 130140 mmHg in comparing prespecied blood pressure targets
patients with type 2 diabetes at high found no signicant reduction in mortality or
risk for CVD (326). The HR for the nonfatal MI. There was a statistically signicant
primary 35% relative reduction in stroke, but the
end point (nonfatal MI, nonfatal stroke, absolute risk reduction was only 1% (330).
and CVD death) in the intensive (blood Microvascular complications were not
pressure 11/64 on 3.4 medications) examined. Another meta- analysis that included
versus standard group (blood pressure both trials comparing blood pressure goals and
143/70 on 2.1 medications) was 0.88 trials comparing treatment strategies
(95% CI 0.731.06; P 5 0.20). Of the concluded that a systolic treatment goal of 130
prespecied secondary end points, only 135 mmHg was acceptable. With goals ,130
stroke and nonfatal stroke were mmHg, there were greater
statistically signicantly reduced by reductions in stroke, a 10% reduction in
mortality, but no reduction of other
intensive blood pressure treatment.
CVD events and increased rates of serious
The number needed to treat to prevent
adverse events. SBP ,130 mmHg was
one stroke over the course of 5 years
associated with reduced
with intensive blood pressure
onset and progression of albuminuria.
management was 89. Serious adverse
However, there was heterogeneity in
event rates (including syncope and
the measure, rates of more advanced renal
hyperkalemia) were higher with
disease outcomes were not
intensive targets (3.3% vs. 1.3%; P 5
affected, and there were no signicant
0.001). Albuminuria rates were reduced changes in retinopathy or neuropathy
with more intensive blood pressure (331).
goals, but there were no differences in
renal function nor in other The clear body of evidence that SBP
microvascular complications. .140 mmHg is harmful suggests that clinicians
should promptly initiate and titrate therapy in
The ADVANCE trial (treatment with an an ongoing fashion to achieve and maintain
ACE inhibitor and a thiazide-type SBP ,140 mmHg in virtually all patients.
diuretic) showed a reduced death rate Additionally, patients with long life expectancy
but not in the composite macrovascular (in whom there may be renal benets from
outcome. However, the ADVANCE trial long-term stricter blood pressure control) or
had no specied targets for the those in whom stroke risk is a concern might, as
randomized comparison and the mean part of shared decision making, appropriately
SBP in the intensive group (135 mmHg) have lower systolic targets such as ,130
was not as low as the mean SBP even in mmHg. This is especially true if it can be
the ACCORD standard-therapy group achieved with few drugs and without side
(327). Post hoc analysis of achieved effects of therapy.
blood pressure in several hypertension
treatment trials have suggested no Treatment Strategies
benet of lower achieved SBP. As an Although there are no well-controlled studies
example, among of diet and exercise in the treatment of
6,400 patients with diabetes and CAD elevated blood pressure or hypertension in
enrolled in one trial, tight control individuals with
(achieved SBP ,130 mmHg) was not diabetes, the DASH study in nondiabetic
associated with improved cardiovascular individuals has shown antihypertensive effects
outcomes compared with usual care similar to pharmacological monotherapy.
Lifestyle therapy consists
(achieved SBP 130140 mmHg) (328).
Similar ndings emerged from an
analysis of another trial. Those with SBP
(,115 mmHg) had increased rates of
CVD events, although they had lower
rates of stroke (329).
of reducing sodium intake In a nonhypertension trial of
(,1,500 mg/ day) and excess high-risk individuals, including a
body weight; increasing large subset with diabetes, an
consumption of fruits, vegetables ACE inhibitor reduced CVD
(810 servings per day), and low- outcomes (338). In patients
fat dairy with congestive heart failure
products (23 servings per day); (CHF), including diabetic
avoiding excessive alcohol subgroups, ARBs have been
consumption (no more than 2 shown to reduce major CVD
servings per day in men and no outcomes (339342), and in
more than 1 serving per day in type 2 diabetic patients with
women) (332); and increasing signicant nephropathy, ARBs
activity levels (320). These were superior to calcium
nonpharmacological strategies channel
may also positively affect
glycemia and lipid control and as a
result should be encouraged in
those with even mildly elevated
blood pressure. Their effects on
cardiovascular events have not
been established.
Nonpharmacological therapy is
reasonable in diabetic individuals
with mildly elevated blood
pressure (SBP
.120 mmHg or DBP .80 mmHg).
If the blood pressure is conrmed
to be $140 mmHg systolic and/or
$80 mmHg
diastolic, pharmacological
therapy should be initiated
along with
nonpharmacological therapy
(320).
Lowering of blood pressure with
regimens based on a variety of
antihypertensive drugs, including
ACE inhibitors, ARBs, b-blockers,
diuretics, and calcium channel
blockers, has been shown to be
effective in reducing
cardiovascular events. Several
studies suggested that ACE
inhibitors may be superior to
dihydropyridine calcium channel
blockers in reducing
cardiovascular events (333335).
However, several studies have shown
no specic advantage to ACE
inhibitors as initial treatment of
hypertension in
the general hypertensive
population, but rather an
advantage on
cardiovascular outcomes of initial
therapy with low-dose
thiazide diuretics
(320,336,337).
In people with diabetes, inhibitors
of the renin-angiotensin system
(RAS) may
have unique advantages for initial
or early therapy of hypertension.
blockers for reducing heart failure conrmed adherence to optimal doses with diabetes. A
(343). Though evidence for distinct of at least three antihypertensive agents
advantages of RAS inhibitors on CVD of different classications, one of which
outcomes in diabetes remains should be a diuretic, clinicians should
conicting (323,337), the high CVD consider an evaluation for secondary
risks associated with diabetes, and the forms of hypertension. Growing
high prevalence of undiagnosed CVD, evidence suggests that there is an
may still favor recommendations for association between increase in sleep-
their use as rst-line hypertension time blood pressure and incidence of
therapy in people with diabetes (320). CVD events. A recent RCT of 448
The blood pressure arm of the ADVANCE participants with type 2 diabetes and
trial demonstrated that routine hypertension demonstrated reduced
administration of a xed combination of cardiovascular events and mortality
the ACE inhibitor perindopril and the with median follow-up of 5.4 years if at
diuretic indapamide signicantly least one antihypertensive medication
reduced combined microvascular and was given at bedtime (345).
macrovascular outcomes, as well as CVD
Pregnancy and Antihypertensives
and total mortality. The improved
In a pregnancy complicated by diabetes
outcomes could also have been due to
and chronic hypertension, target blood
lower achieved blood pressure in the
pressure goals of SBP 110129 mmHg
perindopril-indapamide arm (327).
and DBP 6579 mmHg are reasonable,
Another trial showed a decrease in
as they contribute to improved long-
morbidity and mortality in those
term maternal health. Lower blood
receiving benazepril and amlodipine pressure levels may be associated with
versus benazepril and impaired fetal growth. During
hydrochlorothiazide pregnancy, treatment with ACE
(HCTZ). The compelling benets of RAS inhibitors and ARBs is contraindicated,
inhibitors in diabetic patients with since they may cause fetal damage.
albuminuria or renal insufciency Antihypertensive drugs known to be
provide additional rationale for these effective and safe in pregnancy include
agents (see Section VI.B). If needed to methyldopa, labetalol, diltiazem,
achieve blood pressure targets, clonidine, and prazosin. Chronic diuretic
amlodipine, HCTZ, or chlorthalidone can use during pregnancy has been
be added. If eGFR is ,30 mL/min/m 2, associated with restricted maternal
a loop diuretic, rather than HCTZ or plasma volume, which may reduce
chlorthalidone should be prescribed. uteroplacental perfusion (346).
Titration of and/or addition of further 2. Dyslipidemia/Lipid Management
blood pressure medications should be Recommendations
made in timely fashion to overcome Screening
clinical inertia in achieving blood c In most adult patients with diabetes,
pressure targets. measure fasting lipid prole at least
Health information technology annually. B
potentially can be used as a safe and c In adults with low-risk lipid values
effective tool to enable attainment of (LDL cholesterol ,100 mg/dL, HDL
blood pressure goals. Using a cholesterol .50 mg/dL, and
telemonitoring intervention to direct triglycerides ,150 mg/dL), lipid
titrations of antihypertensive assessments may be repeated every 2
medications between medical ofce years. E
visits has been demonstrated to have a Treatment Recommendations and Goals
profound impact on SBP control (344).
c Lifestyle modication focusing on the
An important caveat is that most reduction of saturated fat, trans fat,
patients with hypertension require and cholesterol intake; increase of n-3
multiple-drug therapy to reach fatty acids, viscous ber and plant
treatment goals (320). Identifying and stanols/ sterols; weight loss (if
addressing barriers to medication indicated); and increased physical
adherence (such as cost and side activity should be recommended to
effects) should routinely be done. If improve the lipid prole in patients
blood pressure is refractory despite
c Statin therapy should be added to lifestyle
therapy, regardless of baseline lipid levels,
for diabetic patients:
c with overt CVD A
c without CVD who are over the age of 40 years
and have one or more other CVD risk factors
(family history of CVD, hypertension,
smoking, dyslipidemia,
or albuminuria). A
c For lower-risk patients than the above (e.g.,
without overt CVD and under the age of 40
years), statin therapy should be considered
in addition to lifestyle therapy if LDL
cholesterol remains above 100 mg/dL or in
those with multiple CVD risk factors. C
c In individuals without overt CVD, the
goal is LDL cholesterol ,100 mg/dL (2.6
mmol/L). B
c In individuals with overt CVD, a lower LDL
cholesterol goal of ,70 mg/dL (1.8
mmol/L), with a high dose of a statin, is an
option. B
c If drug-treated patients do not reach the
above targets on maximum tolerated statin
therapy, a reduction in LDL cholesterol of ;
3040% from baseline is an alternative
therapeutic goal. B
c Triglyceride levels ,150 mg/dL (1.7
mmol/L) and HDL cholesterol .40 mg/dL
(1.0 mmol/L) in men and .50 mg/dL (1.3
mmol/L) in women are
desirable. C However, LDL cholesterol
targeted statin therapy remains the
preferred strategy. A
c Combination therapy has been shown not to
provide additional
cardiovascular benet above statin
therapy alone and is not generally
recommended. A
c Statin therapy is contraindicated in
pregnancy. B
Evidence for Benets of Lipid-
Lowering Therapy
Patients with type 2 diabetes have an
increased prevalence of lipid abnormalities,
contributing to their high risk of CVD. Multiple
clinical trials have demonstrated signicant
effects of pharmacological (primarily statin)
therapy on CVD outcomes in subjects with
CHD and for primary CVD prevention
(347,348). Subanalyses of
diabetic subgroups of larger trials (349353)
and trials specically in subjects with diabetes
(354,355) showed signicant primary and
secondary prevention of CVD events 1/2 CHD
deaths in diabetic patients. Meta- associated with elevated levels, are the most prevalent pattern of
analyses including data from over triglyceride dyslipidemia in persons with type 2
18,000 patients with diabetes from diabetes. However, the evidence base for drugs
14 randomized trials of statin therapy that target these lipid fractions is signicantly
(mean follow-up 4.3 years), less robust than that for statin therapy (363).
demonstrate a 9% proportional Nicotinic acid has
reduction in all-cause mortality, and been shown to reduce CVD outcomes (364),
13% reduction in vascular mortality, although the study was done in a nondiabetic
for each mmol/L reduction in LDL cohort. Gembrozil has been shown to decrease
cholesterol (356). As in those without rates of CVD events in subjects without diabetes
diabetes, absolute reductions in hard (365,366) and in a subgroup with diabetes in one
CVD outcomes (CHD death and of the larger trials (365). However, in a large trial
nonfatal MI) are greatest in people specic to diabetic patients, fenobrate failed to
with high baseline CVD risk (known reduce overall cardiovascular outcomes (367).
CVD and/or very high LDL cholesterol
levels), but the overall benets of Combination Therapy
statin therapy in people with diabetes Combination therapy, with a statin
at moderate or high risk for CVD are and a brate or statin and niacin, may be
convincing (357,358). efcacious for treatment for all three lipid
fractions, but this combination is associated
Diabetes With Statin Use
with an increased risk for abnormal
There is an increased risk of incident
transaminase levels, myositis, or
diabetes with statin use (359,360),
rhabdomyolysis. The risk of rhabdomyolysis is
which may be limited to those with
higher with higher doses of statins and with
diabetes risk factors. These patients
renal insufciency and seems to be lower when
may benet additionally from diabetes
statins are combined with fenobrate than
screening when on statin therapy. In an
gembrozil (368). In the ACCORD study, the
analysis of one of the initial studies
combination of fenobrate and simvastatin did
suggesting that statins are linked to risk
not reduce the rate of fatal cardiovascular events,
of diabetes, the cardiovascular event
nonfatal MI, or nonfatal stroke, as compared
rate reduction with statins outweighed
with simvastatin alone, in patients with type 2
the risk of incident diabetes even for
diabetes who were at high risk for CVD.
patients at highest risk for diabetes
Prespecied subgroup analyses suggested
(361). The absolute risk increase was
heterogeneity in treatment effects according to
small (over 5 years of follow-up, 1.2%
sex, with a benet of combination therapy for
of participants on placebo developed
men and possible harm for women, and a
diabetes and 1.5% on rosuvastatin)
possible benet for patients with both
(362). A meta-analysis of 13 randomized
triglyceride level
statin trials with 91,140 participants
$204 mg/dL and HDL cholesterol level
showed an odds ratio of 1.09 for a new
#34 mg/dL (369). The AIM-HIGH trial
diagnosis of diabetes, so that (on
randomized over 3,000 patients (about one-third
average) treatment of 255 patients with
with diabetes) with established CVD, low levels
statins for
of HDL cholesterol, and triglyceride levels of 150
4 years resulted in one additional case
400 mg/dL to statin therapy plus extended
of diabetes, while simultaneously
release niacin or matching placebo. The trial was
preventing 5.4 vascular events among
halted early due to lack of efcacy on the
those 255 patients (360). The relative
primary CVD outcome (rst event of the
risk- benet ratio favoring statins is
composite of death from coronary heart disease
further supported by meta-analysis of
(CHD), nonfatal MI, ischemic stroke,
individual data of over 170,000 persons
hospitalization for an acute coronary syndrome,
from 27 randomized trials. This
or symptom-driven coronary or cerebral
demonstrated that individuals at low
revascularization) and a possible increase in
risk of vascular disease, including those
ischemic stroke in those on combination therapy
undergoing primary prevention,
(370).
received benets from statins that
included reductions in major vascular
events and vascular death without
increase in incidence of cancer or deaths
from other causes (348).
Low levels of HDL cholesterol, often
Hence, combination lipid- proportionately similar
lowering therapy cannot be reduction in risk to patients
broadly recommended. with type 2 diabetes,
Dyslipidemia Treatment and Target although not statistically signicant
Lipid Levels (350). Although the data are not
Unless they have severe denitive, similar lipid-
hypertriglyceridemia at risk for lowering goals for both type
pancreatitis, for most diabetic 1 and type 2 diabetic
patients the rst priority of
dyslipidemia therapy is to lower
LDL cholesterol to ,100 mg/dL
(2.60 mmol/L) (371). Lifestyle
intervention, including MNT,
increased physical activity, weight
loss, and smoking cessation, may
allow some patients to reach lipid
goals. Nutrition intervention
should be tailored according to
each patients age,
diabetes type, pharmacological
treatment, lipid levels, and other
medical conditions.
Recommendations should focus
on the reduction of saturated fat,
cholesterol, and trans
unsaturated fat intake and
increases in
n-3 fatty acids, viscous ber (such
as in oats, legumes, and citrus),
and plant stanols/sterols.
Glycemic control can also
benecially modify plasma lipid
levels, particularly in patients with
very high triglycerides and poor
glycemic control.
In those with clinical CVD or over age
40 years with other CVD risk
factors, pharmacological
treatment should be added to
lifestyle therapy regardless of
baseline lipid levels. Statins are
the drugs of choice for LDL
cholesterol lowering and
cardioprotection. In patients
other than those described
above, statin treatment should be
considered if there is an
inadequate LDL cholesterol
response to lifestyle
modications and improved
glucose control or if the patient
has increased cardiovascular risk
(e.g., multiple cardiovascular risk
factors or long
diabetes duration).
Very little clinical trial evidence
exists for type 2 diabetic patients
under the age of 40 years or for
type 1 diabetic patients of any
age. In the Heart Protection
Study (lower age limit 40 years),
the subgroup of ;600 patients
with type 1 diabetes had a
S4040 Position Diabetes Care Volume 37, Supplement 1, January 2014
Statement

patients should be considered, doses of statins fail to signicantly lower Table 10 summarizes common
particularly if they have other LDL cholesterol (,30% reduction from treatment goals for A1C, blood
cardiovascular risk factors. the patients baseline), there is no pressure, and LDL cholesterol.
Alternative Lipoprotein Goals strong evidence that combination
Most trials of statins and CVD outcome therapy should be used to achieve 3. Antiplatelet Agents
tested specic doses of statins against additional LDL cholesterol lowering. Recommendations
placebo or other statins, rather than Niacin, fenobrate, ezetimibe, and bile c Consider aspirin therapy (75162 mg/
aiming for specic LDL cholesterol goals acid sequestrants all offer additional day) as a primary prevention strategy
(372). Placebo-controlled trials LDL cholesterol lowering to statins in those with type 1 or type 2 diabetes
generally achieved LDL cholesterol alone. However, there is insufcient at increased cardiovascular risk (10-
reductions of evidence that such combination therapy year risk .10%). This includes most
3040% from baseline. Hence, LDL for LDL cholesterol lowering provides a men aged .50 years or women aged
cholesterol lowering of this magnitude signicant increment in CVD risk .60 years who have at least one
is an acceptable outcome for patients reduction over statin therapy alone. additional major risk factor (family
who cannot reach LDL cholesterol goals history of CVD, hypertension, smoking,
due to severe baseline elevations in LDL Treatment of Other Lipoprotein dyslipidemia, or albuminuria). C
cholesterol and/or intolerance of Fractions or Targets c Aspirin should not be recommended
maximal, or any, statin doses. Hypertriglyceridemia should be for CVD prevention for adults with
Additionally for those with baseline LDL addressed with dietary and lifestyle diabetes at low CVD risk (10-year CVD
cholesterol minimally above 100 mg/dL, changes. Severe hypertriglyceridemia risk ,5%, such as in men aged ,50
prescribing statin therapy to lower LDL (.1,000 mg/dL) may warrant years and women aged ,60 years
cholesterol about 3040% from baseline immediate pharmacological therapy with no major additional CVD risk
is probably more effective than (bric acid derivative, niacin, or sh factors), since the potential adverse
prescribing just enough to get LDL oil) to reduce the risk of acute effects from bleeding likely offset the
cholesterol slightly below 100 mg/dL. pancreatitis. If severe potential benets. C
Clinical trials in high-risk patients, such hypertriglyceridemia is absent, then c In patients in these age-groups
as those with acute coronary syndromes therapy targeting HDL cholesterol or with multiple other risk factors (e.g.,
or previous cardiovascular events (373 triglycerides lacks the strong evidence 10-year risk 510%), clinical judgment
375), have demonstrated that more base of statin therapy. If the HDL is required. E
aggressive therapy with high doses of cholesterol is ,40 mg/dL and the LDL c Use aspirin therapy (75162 mg/day)
statins to achieve an LDL cholesterol of cholesterol between 100 and 129 as a secondary prevention strategy in
,70 mg/dL led to a signicant mg/dL, a brate or niacin might be used, those with diabetes with a history of
reduction in further events. A reduction especially if a patient is intolerant to CVD. A
in LDL cholesterol to ,70 mg/dL is an statins. Niacin is the most effective drug c For patients with CVD and documented
option in very-high-risk diabetic for raising HDL cholesterol. It can aspirin allergy, clopidogrel (75 mg/day)
patients with overt CVD (371). Some signicantly increase blood glucose at should be used. B
experts recommend a greater focus on high doses, but at modest doses (750 c Dual antiplatelet therapy is
non-HDL cholesterol, apolipoprotein B 2,000 mg/day), signicant reasonable for up to a year after an
(apoB), or lipoprotein particle improvements in LDL cholesterol, HDL acute coronary syndrome. B
measurements to assess residual CVD cholesterol, and triglyceride levels are
risk in statin-treated patients who are accompanied by only modest changes in Aspirin has been shown to be effective
likely to have small LDL particles, such as glucose that are generally amenable to in reducing cardiovascular morbidity
people with diabetes (376), but it is adjustment of diabetes therapy and mortality in high-risk patients with
unclear whether clinical management (370,379,380).
would change with these
measurements.
In individual patients, the high variable
response seen with LDL cholesterol doses (378). When maximally tolerated
lowering with statins is poorly
understood (377). Reduction of CVD
events with statins correlates very
closely with LDL cholesterol lowering
(347). If initial attempts to prescribe a
statin leads to side effects, clinicians
should attempt to nd a dose or
alternative statin that is tolerable.
There is evidence for signicant LDL
cholesterol lowering from even
extremely low, less than daily, statin
care.diabetesjournals.org Position Statement
Table 10Summary of recommendations for S4141
glycemic, blood pressure, and lipid control
for most adults with diabetes
A1C ,7.0%*
Blood
pressure
,140/80
mmHg**
Lipids
LDL cholesterol ,100 mg/dL (,2.6
mmol/L)
Statin therapy
for those with
history of MI
or age over
40 plus other
risk factors
*More or less stringent glycemic goals may be
appropriate for individual patients. Goals should be
individualized based on duration of diabetes, age/life
expectancy, comorbid conditions, known CVD or
advanced microvascular complications,
hypoglycemia unawareness, and individual patient
considerations. **Based on patient characteristics
and response to therapy, lower SBP targets may be
appropriate. In individuals with overt CVD, a lower
LDL cholesterol goal of ,70 mg/dL (1.8 mmol/L),
using a high dose of a statin, is an option.
previous MI or stroke (secondary number of episodes of bleeding do not have equal effects on long-term health
prevention). Its net benet in primary induced, although these (384).
prevention among patients with no complications
In 2010, a position statement of the ADA, the
previous cardiovascular events is more
American Heart Association (AHA), and the
controversial, both for patients with and
American College of Cardiology Foundation
without a history of diabetes (381,382).
(ACCF) recommends that low-dose (75162
Two RCTs of aspirin specically in
mg/day) aspirin for primary prevention is
patients with diabetes failed to show a
reasonable for adults with diabetes and no
signicant reduction in CVD end points,
raising further questions about the previous history of vascular disease who are at
efcacy of aspirin for primary increased CVD risk
prevention in people with diabetes (10-year risk of CVD events over 10%) and who
(190,383). are not at increased risk for bleeding. This
generally includes most men over age 50 years
The Antithrombotic Trialists (ATT) and women over age 60 years who also have
collaborators published an individual one or more of the following major risk factors:
patient-level meta-analysis of the six 1) smoking,
large trials of aspirin for primary 2) hypertension, 3) dyslipidemia, 4) family history
prevention in the general population. of premature CVD, and 5) albuminuria (385).
These trials collectively enrolled over
95,000 participants, including almost However, aspirin is no longer recommended for
4,000 with diabetes. Overall, they found those at low CVD risk (women under age 60
that aspirin reduced the risk of vascular years and men under age 50 years with no
events by 12% (RR 0.88 [95% CI 0.82 major CVD risk factors; 10-year CVD risk under
0.94]). The largest reduction was for 5%) as the low benet is likely to be
nonfatal MI with little effect on CHD outweighed by the risks of signicant bleeding.
death (RR 0.95 [95% CI 0.781.15]) or Clinical judgment should be used for those at
total stroke. There was some evidence intermediate risk (younger patients with one or
of a difference in aspirin effect by sex: more risk factors or older patients with no risk
aspirin signicantly reduced CVD factors; those with 10-year CVD risk of
events in men, but not in women. 510%) until further research is available. Aspirin
Conversely, use in patients under the age of
aspirin had no effect on stroke in men 21 years is contraindicated due to the
but associated risk of Reye syndrome.
signicantly reduced stroke in women. Average daily dosages used in most clinical
Notably, sex differences in aspirins trials involving patients with
effects have not been observed in diabetes ranged from 50 to 650 mg but were
studies of secondary prevention (381). mostly in the range of 100 to 325 mg/day.
In the six trials examined by the ATT There is little evidence to
collaborators, the effects of aspirin on support any specic dose, but using the lowest
major vascular events were similar for possible dosage may help reduce side effects
patients with or without diabetes: RR (386). In the U.S., the most common low dose
0.88 (95% CI 0.67 tablet is 81 mg.
1.15) and 0.87 (0.790.96), Although platelets from patients with diabetes
respectively. The condence interval have altered function, it is unclear what, if any,
was wider for those with diabetes impact that nding has on the required dose of
because of their smaller number.
aspirin for cardioprotective effects in the
Based on the currently available patient with diabetes. Many alternate pathways
evidence, aspirin appears to have a for platelet activation exist that are
modest effect on ischemic vascular independent of thromboxane A2 and thus not
events with the absolute decrease in sensitive to the effects of aspirin (387).
events depending on the underlying Therefore, while aspirin resistance appears
CVD risk. The main adverse effects higher in the
appear to be an increased risk of diabetic patients when measured by a
gastrointestinal bleeding. The excess
risk may be as high as 15 per 1,000 per
year in real-world settings. In adults
with CVD risk greater than 1% per year,
the number of CVD events prevented
will be similar to or greater than the
variety of ex vivo and in vitro albuminuria at 1 year (389).
methods (platelet aggrenometry, The routine and thorough assessment
measurement of thromboxane of tobacco use is key to prevent
B2), these observations alone are smoking or encourage
insufcient to empirically cessation. Numerous
recommend higher doses of large randomized clinical trials
aspirin be used in the diabetic have demonstrated the
patient at this time. efcacy and cost-
A P2Y12 receptor antagonist in effectiveness of brief
combination with aspirin should counseling
be used for at least 1 year in in smoking cessation, including
patients following an acute the use of quitlines, in
coronary syndrome. Evidence reducing tobacco use.
supports use of either ticagrelor
or
clopidogrel if no percutaneous
coronary intervention (PCI) was
performed, and the use of
clopidogrel, ticagrelor, or
prasugrel if PCI was performed
(388).

4. Smoking Cessation
Recommendations
c Advise all patients not to
smoke or use tobacco
products. A
c Include smoking cessation
counseling and other forms of
treatment as a routine
component of diabetes care. B

Results from epidemiological,


case- control, and cohort studies
provide convincing evidence to
support the causal link between
cigarette smoking and health
risks. Much of the work
documenting the effect of
smoking on health did not
separately discuss results on
subsets of individuals with
diabetes, but suggests that the
identied risks are at least
equivalent to those found in the
general population. Other studies
of
individuals with diabetes
consistently demonstrate that
smokers (and persons exposed to
second-hand smoke) have a
heightened risk of CVD,
premature death, and increased
rate of microvascular
complications of diabetes.
Smoking may have a role in the
development of type 2 diabetes.
One study in smokers with newly
diagnosed type 2 diabetes found
that smoking cessation was
associated with amelioration of
metabolic parameters and
reduced blood pressure and
For the patient motivated to quit, the recommended to reduce CVD events in burden have more future cardiac events
addition of pharmacological therapy to overweight or obese adults with type 2 (400402), the role of these tests
counseling is more effective than either diabetes (155). Patients at increased beyond risk stratication is not clear.
treatment alone. Special considerations CVD risk should receive aspirin and a Their routine use leads to radiation
should include assessment of level statin, and ACE inhibitor or ARB exposure and may result in unnecessary
of nicotine dependence, which is therapy if hypertensive, unless there invasive testing such as coronary
associated with difculty in quitting and are contraindications to a particular angiography and revascularization
relapse (390). Although some patients drug class. While clear benet exists procedures. The ultimate balance of
may gain weight in the period shortly for ACE inhibitor and ARB therapy in benet, cost, and risks of such an
after smoking cessation, recent research patients with nephropathy or approach in asymptomatic patients
has demonstrated that this weight gain hypertension, the benets in patients remains controversial, particularly in
does not diminish the substantial CVD with CVD in the absence of these the modern setting of aggressive CVD
risk benet realized from smoking conditions are less clear, especially risk factor control.
cessation (391). when LDL cholesterol is concomitantly A systematic review of 34,000 patients
controlled (392,393). showed that metformin is as safe as
5. Cardiovascular Disease other glucose-lowering treatments in
Candidates for advanced or invasive
Recommendations
cardiac testing include those with patients with diabetes and CHF, even in
Screening
1) typical or atypical cardiac symptoms those with reduced left ventricular
c In asymptomatic patients, routine and 2) an abnormal resting ECG. The ejection fraction or concomitant
screening for CAD is not screening of asymptomatic patients chronic kidney disease (CKD); however,
recommended because it does not with high CVD risk is not recommended metformin should be avoided in
improve outcomes as long as CVD (257), in part because these high-risk hospitalized patients (403).
risk factors are treated. A patients should already be receiving
Treatment intensive medical therapy, an approach B. Nephropathy
that provides similar bene t as invasive General Recommendations
c In patients with known CVD, consider
revascularization (394,395). There is c Optimize glucose control to reduce
ACE inhibitor therapy C and use
also some evidence that silent MI may the risk or slow the progression of
aspirin and statin therapy A (if not
reverse over time, adding to the nephropathy. A
contraindicated) to reduce the risk of
controversy concerning aggressive c Optimize blood pressure control to
cardiovascular events.
screening strategies (396). Finally, a reduce the risk or slow the
c In patients with a prior MI, b-
recent randomized observational trial progression of nephropathy. A
blockers should be continued for at
demonstrated no clinical benet to
least 2 years after the event. B Screening
routine screening of asymptomatic
c In patients with symptomatic heart Perform an annual test to quantitate
patients with type 2 diabetes and c
failure, avoid thiazolidinedione urine albumin excretion in type 1
normal ECGs (397). Despite abnormal
treatment. C diabetic patients with diabetes
myocardial perfusion imaging in more
c In patients with stable CHF, duration of $5 years and in all type 2
than one in ve patients, cardiac
metformin may be used if renal diabetic patients starting at
outcomes were essentially equal (and
function is normal but should be diagnosis. B
avoided in unstable or hospitalized very low) in screened versus unscreened
patients with CHF. B patients. Accordingly, the overall Treatment
effectiveness, especially the cost-
c An ACE inhibitor or ARB for the
In all patients with diabetes, effectiveness, of such an indiscriminate
primary prevention of diabetic kidney
cardiovascular risk factors should be screening strategy is now questioned.
disease is not recommended in
assessed at least annually. These risk Despite the intuitive appeal, recent diabetic patients with normal blood
factors include dyslipidemia, studies have found that a risk factor pressure and albumin excretion ,30
hypertension, smoking, a positive family based approach to the initial diagnostic mg/24 h. B
history of premature coronary disease, evaluation and subsequent follow-up c Either ACE inhibitors or ARBs (but not
and the presence of albuminuria. for CAD fails to identify which patients both in combination) are
Abnormal risk factors should be treated with type 2 diabetes will have silent recommended for the treatment of
as described elsewhere in these ischemia on screening tests (398,399). the nonpregnant patient with
guidelines. Intensive lifestyle The effectiveness of newer noninvasive modestly elevated (30299 mg/24 h)
intervention focusing on weight loss CAD screening methods, such as C or higher levels (.300 mg/24 h) of
through decreased caloric intake and computed tomography (CT) and CT urinary albumin excretion. A
increased physical activity as performed angiography, to identify patient c For people with diabetes and diabetic
in the Look AHEAD trial may be subgroups for different treatment kidney disease (albuminuria .30 mg/
considered for improving glucose strategies remains unproven. Although 24 h), reducing the amount of dietary
control, tness, and some CVD risk asymptomatic diabetic patients found protein below usual intake is not
factors. However, it is not to have a higher coronary disease recommended because it does not
alter glycemic measures, A number of interventions have been Combinations of drugs that block the
cardiovascular risk measures, or the demonstrated to reduce the risk and
course of GFR decline. A slow the progression of renal disease.
c When ACE inhibitors, ARBs, or Intensive diabetes management
diuretics are used, monitor serum with the goal of achieving near-
creatinine and potassium levels for normoglycemia has been shown in large
the development of increased prospective randomized studies to
creatinine or changes in potassium. E delay the onset and progression of
c Continued monitoring of urine increased urinary albumin excretion in
albumin excretion to assess both patients with type 1 (413) and type 2
response to therapy and (85,86,89,90) diabetes. The UKPDS
progression of disease is provided strong evidence that blood
reasonable. E pressure control can reduce the
c When eGFR is ,60 mL/min/1.73 m2, development of nephropathy (323). In
evaluate and manage potential addition, large prospective randomized
complications of CKD. E studies in patients with type 1 diabetes
c Consider referral to a physician have demonstrated that achievement
experienced in the care of kidney of lower levels of SBP (,140 mmHg)
disease for uncertainty about the resulting from treatment using ACE
etiology of kidney disease, inhibitors provides a selective benet
difcult management issues, or over other antihypertensive drug
advanced kidney disease. B classes in delaying the progression of
increased urinary albumin excretion
To be consistent with newer and can slow the decline in GFR in
nomenclature intended to emphasize patients with higher levels of
the continuous nature of albuminuria albuminuria (414,415). In type 2
as a risk factor, the terms diabetes with hypertension and
microalbuminuria (30299 mg/24 h) normoalbuminuria, RAS inhibition has
and macroalbuminuria (.300 been demonstrated to delay onset of
mg/24 h) will no longer be used, but elevated albuminuria (416,417). In the
rather referred to as persistent latter study, there was an unexpected
albuminuria at levels 30299 mg/24 h higher rate of fatal cardiovascular
events with olmesartan among patients
and levels $300 mg/24 h. Normal
with preexisting CHD.
albumin excretion is currently dened
as ,30 mg/24 h. ACE inhibitors have been shown to
reduce major CVD outcomes (i.e., MI,
Diabetic nephropathy occurs in 2040%
stroke, death) in patients with diabetes
of patients with diabetes and is the
(338), thus further supporting the use of
single leading cause of ESRD. Persistent
these agents in patients with elevated
albuminuria in the range of 30299 mg/
albuminuria, a CVD risk factor. ARBs do
24 h has been shown to be an early not prevent onset of elevated
stage of diabetic nephropathy in type 1 albuminuria in normotensive patients
diabetes and a marker for development with type 1 or type 2 diabetes
of nephropathy in type 2 diabetes. It is (418,419); however, ARBs have been
a well-established marker of increased shown to reduce the progression rate
CVD risk (404406). However, there is of albumin levels from 30 to 299 mg/24
increasing evidence of spontaneous h to levels
remission of albumin levels 30299 mg/ $300 mg/24 h as well as ESRD in
24 h in up to 40% of patients with type patients with type 2 diabetes (420
1 diabetes. About 3040% remain with 422). Some evidence suggests that ARBs
30299 mg/24 h and do not progress to have a smaller magnitude of rise in
more elevated levels of albuminuria potassium compared with ACE inhibitors
($300 mg/24 h) over 510 years of in people with nephropathy (423).
follow-up (407410). Patients with In the absence of side effects or adverse
persistent albuminuria (30299 mg/24 events (e.g., hyperkalemia or acute
h) who progress to more signicant kidney injury), it is suggested to titrate
levels ($300 mg/24 h are likely to up to the maximum approved dose for
progress to ESRD (411,412). the treatment of hypertension.
renin-angiotensin-aldosterone expensive but
system (e.g., an ACE inhibitor plus susceptible to false-
an ARB, a mineralocorticoid negative and
antagonist, or a direct renin -positive determinations as a
inhibitor) provide additional result of variation in urine
lowering of albuminuria (424 concentration due to hydration
427). However, such and other factors.
combinations have been found to Abnormalities of albumin
provide no additional excretion and the linkage
cardiovascular benet and have between albumin-to-creatinine
higher adverse event rates (428).
At least one randomized clinical
trial has shown an increase in
adverse events, particularly
impaired kidney function and
hyperkalemia, compared with
either
agent alone, despite a reduction in
albuminuria using combination therapy
(410).
Diuretics, calcium channel
blockers, and b-blockers should
be used as additional therapy to
further lower blood pressure in
patients already treated with ACE
inhibitors or ARBs (343) or as
alternate therapy in the rare
individual unable to tolerate ACE
inhibitors or ARBs.
Studies in patients with varying
stages of nephropathy have
shown that protein restriction of
dietary protein helps slow the
progression of albuminuria, GFR
decline, and occurrence of ESRD (429
432), although more recent
studies have provided conicting
results (157). Dietary protein
restriction might be considered
particularly in patients whose
nephropathy seems to be
progressing despite optimal
glucose and blood pressure
control and use of ACE inhibitor
and/or ARBs (432).

Assessment of Albuminuria Status and


Renal Function
Screening for increased urinary
albumin excretion can be
performed by measurement of
the albumin-to- creatinine ratio in
a random spot collection; 24-h or
timed collections are more
burdensome and add little to
prediction or accuracy (433,434).
Measurement of a spot urine for
albumin alone (whether by
immunoassay or by using a
dipstick test specic for
albuminuria) without
simultaneously measuring
urine creatinine is less
ratio and 24-h albumin excretion disease, or electrolyte disturbance) or
Table 12Stages of chronic kidney disease
are dened in Table 11. Because of 2
GFR (mL/min/1.73 m body
variability in urinary albumin
St ag e De sc ri pti on su rf a ce a rea )
excretion, two of three specimens
collected within a 3- to 6-month period
should be abnormal before considering a 2 Kidney damage* with mildly decreased GFR 6089
patient to have developed increased 3 Moderately decreased GFR 3059
urinary albumin excretion or had a 4 Severely decreased GFR 1529
progression in albuminuria. Exercise 5 K id ney fa il ur e , 15 or di a lys
within 24 h, infection, fever, CHF, is
marked hyperglycemia, and marked *Kidney damage dened as abnormalities on pathologic, urine, blood, or imaging tests.
hypertension may elevate urinary Adapted from Levey et al. (434).
albumin excretion over baseline
values. CKD-EPI equation. GFR calculators are
available at http://www.nkdep.nih.gov.
Information on presence of abnormal
urine albumin excretion in addition to The role of continued annual
level of GFR may be used to stage CKD. quantitative assessment of albumin
The National Kidney Foundation excretion after diagnosis of albuminuria
classication (Table 12) is primarily and institution of ACE inhibitor or ARB
based on GFR levels and may be therapy and blood pressure control is
superseded by other systems in which unclear. Continued surveillance can
staging includes other variables such assess both response to therapy and
as urinary albumin excretion (435). progression of disease. Some suggest
Studies have found decreased GFR in that reducing albuminuria to the normal
the absence of increased urine albumin (,30 mg/g) or near-normal range may
excretion in a substantial percentage improve renal and cardiovascular
of adults with diabetes (436). prognosis, but this approach has not
Substantial evidence shows that in been formally evaluated in prospective
patients with type 1 diabetes and trials, and more recent evidence
persistent albumin levels 30299 reported spontaneous remission of
mg/24 h, screening with albumin albuminuria in up to 40% of type 1
excretion rate alone would miss .20% diabetic patients.
of progressive disease (410). Serum Conversely, patients with increasing
creatinine with estimated GFR should albumin levels, declining GFR, increasing
therefore be assessed at least annually blood pressure, retinopathy,
in all adults with diabetes, regardless macrovascular disease, elevated lipids
of the degree of urine albumin and/or uric acid concentrations, or
excretion. a family history of CKD are more likely
Serum creatinine should be used to to experience a progression of diabetic
estimate GFR and to stage the level of kidney disease (410).
CKD, if present. eGFR is commonly Complications of kidney disease
coreported by laboratories or can be correlate with level of kidney function.
estimated using formulae such as the When the eGFR is ,60 mL/min/1.73
Modication of Diet in Renal Disease m2, screening for complications of CKD
(MDRD) study equation (437) or the is indicated (Table 13). Early
vaccination against HBV is indicated in
patients likely to progress to end-stage
kidney disease.
Table 11Denitions of Consider referral to a physician
abnormalities in albumin excretion experienced in the care of kidney
Spot collection disease when there is uncertainty about
Ca te gor y ( mg /m g cr ea tin the etiology of kidney disease (heavy
in e )
proteinuria, active urine sediment,
Normal urinary
Increased ,30
$30 absence of retinopathy, rapid decline in
al bumi n excretio n* GFR, and resistant hypertension). Other
*Historically, ratios between 30 and 299 triggers for referral may include difcult
have been called microalbuminuria and management issues (anemia, secondary
those 300 or greater have been called hyperparathyroidism, metabolic bone
macroalbuminuria (or clinical albuminuria).
advanced kidney disease. The threshold for
referral may vary depending on the frequency
with which a provider
encounters diabetic patients with signicant
kidney disease. Consultation with a
nephrologist when stage 4 CKD
develops has been found to reduce cost,
improve quality of care, and keep people off
dialysis longer (438).
However, nonrenal specialists should
not delay educating their patients about the
progressive nature of diabetic kidney disease,
the renal preservation
benets of aggressive treatment of blood
pressure, blood glucose, and
hyperlipidemia, and the potential need for
renal transplant.

C. Retinopathy
General Recommendations
c Optimize glycemic control to reduce the
risk or slow the progression of retinopathy.
A
c Optimize blood pressure control to
reduce the risk or slow the progression of
retinopathy. A
Screening
c Adults with type 1 diabetes should have
an initial dilated and
comprehensive eye examination by
an ophthalmologist or optometrist within
5 years after the onset of diabetes. B
c Patients with type 2 diabetes should have
an initial dilated and
comprehensive eye examination by an
ophthalmologist or optometrist shortly
after the diagnosis of diabetes. B
c If there is no evidence of retinopathy
for one or more eye exams, then exams
every 2 years may be
considered. If diabetic retinopathy is
present, subsequent examinations
for type 1 and type 2 diabetic patients
Table 13Management of CKD in diabetes although tight targets (systolic ,120
GFR Re co mme nd ed
mmHg) do not impart additional benet
(442). Several case series and a
All patients Yearly measurement of creatinine, urinary albumin excretion, potassium
controlled prospective study suggest
4560 Referral to a nephrologist if possibility for nondiabetic kidney disease exists that pregnancy in type 1 diabetic
(duration of type 1 diabetes ,10 years, heavy proteinuria, abnormal
patients may aggravate retinopathy
ndings on renal ultrasound, resistant hypertension, rapid fall in GFR, or
active urinary sediment on ultrasound) (443,444). Laser photocoagulation
Consider need for dose adjustment of medications surgery can minimize this risk (444).
Monitor eGFR every 6 months One of the main motivations for
Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus,
parathyroid hormone at least yearly
screening for diabetic retinopathy is the
Assure vitamin D sufciency long-established efcacy of laser
Consider bone density testing photocoagulation surgery in preventing
Referral for dietary counseling visual loss. Two large trials, the Diabetic
3044 Monitor eGFR every 3 months Retinopathy Study (DRS) in patients
Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid with PDR and the Early Treatment
hormone, hemoglobin, albumin, weight every 36 months Diabetic Retinopathy Study (ETDRS) in
Consider need for dose adjustment of medications patients with macular edema, provide
, 30 Re fer r al to a nep hr ol ogi st the strongest support for the
Adapted from http://www.kidney.org/professionals/KDOQI/guideline_diabetes. therapeutic benets of
photocoagulation surgery. The DRS
(445) showed that panretinal
should be repeated annually by an loss in patients with high-risk PDR, photocoagulation surgery reduced the
ophthalmologist or optometrist. If clinically signicant macular edema, risk of severe vision loss from PDR from
retinopathy is progressing or sight and in some cases severe NPDR. A 15.9% in untreated eyes to 6.4% in
threatening, then examinations will c Anti-vascular endothelial growth treated eyes, with greatest risk-benet
be required more frequently. B factor (VEGF) therapy is indicated for ratio in those with baseline disease
c High-quality fundus photographs can diabetic macular edema. A (disc neovascularization or vitreous
detect most clinically signicant c The presence of retinopathy is not a hemorrhage).
diabetic retinopathy. Interpretation contraindication to aspirin therapy The ETDRS (446) established the benet
of the images should be performed for cardioprotection, as this therapy of focal laser photocoagulation surgery
by a trained eye care provider. While does not increase the risk of retinal in eyes with macular edema,
retinal photography may serve as a hemorrhage. A particularly those with clinically
screening tool for retinopathy, it is signicant macular edema, with
not a substitute for a comprehensive Diabetic retinopathy is a highly specic reduction of doubling of the visual
eye exam, which should be vascular complication of both type 1 and angle (e.g., 20/50 to 20/100) from 20%
performed at least initially and at type 2 diabetes, with prevalence in untreated eyes to 8%
intervals thereafter as recommended strongly related to the duration of in treated eyes. The ETDRS also
by an eye care professional. E diabetes. Diabetic retinopathy is the veried the benets of panretinal
c Women with preexisting diabetes most frequent cause of new cases of photocoagulation for high-risk PDR and
who are planning pregnancy or who blindness among adults aged 2074 in older-onset patients with severe
have become pregnant should have a years. Glaucoma, cataracts, and other NPDR or less-than-high-risk PDR.
comprehensive eye examination disorders of the eye occur earlier and
and be counseled on the risk of more frequently in people with Laser photocoagulation surgery in both
development and/or progression diabetes. trials was benecial in reducing the risk
of diabetic retinopathy. Eye of further visual loss, but generally not
In addition to duration of diabetes, benecial in reversing already
examination should occur in the rst
factors that increase the risk of, or are diminished acuity. Recombinant
trimester with close follow-up
throughout pregnancy and for 1 year associated with, retinopathy include monoclonal neutralizing antibody to
postpartum. B chronic hyperglycemia (439), VEGF improves vision and reduces the
nephropathy (440), and hypertension need for laser photocoagulation in
Treatment (441). Intensive diabetes management patients with macular edema (447).
c Promptly refer patients with any level with the goal of achieving near- Other emerging therapies for
of macular edema, severe NPDR, or normoglycemia has been shown in large retinopathy include sustained
any PDR to an ophthalmologist who is prospective randomized studies to intravitreal delivery of uocinolone
knowledgeable and experienced in prevent and/or delay the onset and (448) and the possibility of prevention
the management and treatment of progression of diabetic retinopathy with fenobrate (449,450).
diabetic retinopathy. A (76,85,86,442). Lowering blood
Laser photocoagulation therapy is The preventive effects of therapy and
c pressure has been shown to decrease
indicated to reduce the risk of vision the fact that patients with PDR or
the progression of retinopathy (323),
macular edema may be asymptomatic
provide strong support for a screening diagnosis of type 1 diabetes and at Effective symptomatic treatments are
program to detect diabetic least annually thereafter, using available for the neuropathic pain of
retinopathy. Because retinopathy is simple clinical tests. B DPN such as neuropathic pain (455)
estimated to take at least 5 years to c Electrophysiological testing or and for limited symptoms of
develop after the onset of referral to a neurologist is rarely autonomic neuropathy.
hyperglycemia, patients with type 1 needed, except in situations Diagnosis of Neuropathy
diabetes should have an initial dilated where the clinical features are
and comprehensive eye examination Distal Symmetric Polyneuropathy. Patients
atypical. E with diabetes should be screened
within 5 years after the diabetes (451). c Screening for signs and symptoms of
Patients with type 2 diabetes, who annually for DPN symptoms using
CAN should be instituted at diagnosis simple clinical tests. Symptoms vary
may have had years of undiagnosed
of type 2 diabetes and 5 years after according to the class of sensory bers
diabetes and who have a signicant
the diagnosis of type 1 diabetes. involved. The most common symptoms
risk of prevalent diabetic retinopathy
Special testing is rarely needed and are induced by the involvement of small
at time of diagnosis should have an
may not affect management or bers and include pain, dysesthesias
initial dilated and comprehensive eye
outcomes. E (unpleasant abnormal sensations of
examination. Examinations should be
c Medications for the relief of specic burning and tingling associated with
performed by an ophthalmologist or
optometrist who is knowledgeable symptoms related to painful DPN and peripheral nerve lesions), and
and experienced in diagnosing autonomic neuropathy are numbness. Clinical tests include
diabetic retinopathy. Subsequent recommended because they may assessment of vibration threshold
examinations for type 1 and type 2 reduce pain B and improve quality of using a 128-Hz tuning fork, pinprick
diabetic patients are generally life. E sensation and light touch perception
repeated annually. Exams every 2 years using a 10-g monolament, and ankle
may be cost-effective after one or The diabetic neuropathies are reexes. Assessment should follow the
more normal eye exams, and in a heterogeneous with diverse clinical typical DPN pattern, starting distally
population with well-controlled type 2 manifestations. They may be focal or (the dorsal aspect of the hallux) on both
diabetes there was essentially no risk diffuse. The most prevalent sides and move proximally until
of development of signicant neuropathies are chronic sensorimotor threshold is detected. Several clinical
retinopathy with a 3-year interval DPN and autonomic neuropathy. instruments that combine more than
after a normal examination (452). Although DPN is a diagnosis of one test have .87% sensitivity in
Examinations will be required more exclusion, complex investigations or detecting DPN (83,456,457).
frequently if retinopathy is referral for neurology consultation to In patients with severe or atypical
progressing. exclude other conditions is rarely neuropathy, causes other than diabetes
Retinal photography, with remote needed. should always be considered, such as
reading by experts, has great potential neurotoxic medications, heavy metal
The early recognition and appropriate
in areas where qualied eye care poisoning, alcohol abuse, vitamin B12
management of neuropathy in the
professionals are not available. It may patient with diabetes is important for a deciency (especially in those taking
also enhance efciency and reduce costs number of reasons: metformin for prolonged periods)
when the expertise of ophthalmologists (458), renal disease, chronic
can be used for more complex 1. Nondiabetic neuropathies may be inammatory demyelinating
examinations and for therapy (453). In- present in patients with diabetes and neuropathy, inherited neuropathies,
person exams are still necessary when may be treatable. and vasculitis (459).
the photos are unacceptable and for 2. A number of treatment options exist Diabetic Autonomic Neuropathy. The
follow-up of abnormalities detected. for symptomatic diabetic symptoms and signs of autonomic
Photos are not a substitute for a neuropathy. dysfunction should be elicited carefully
comprehensive eye exam, which should 3. Up to 50% of DPN may be during the history and physical
be performed at least initially and at asymptomatic and patients are at examination. Major clinical
intervals thereafter as recommended by risk for insensate injury to their feet. manifestations of diabetic autonomic
an eye care professional. Results of eye 4. Autonomic neuropathy and neuropathy include resting tachycardia,
examinations should be documented particularly CAN is an independent exercise intolerance, orthostatic
and transmitted to the referring health risk factor for cardiovascular hypotension, constipation,
care professional. mortality (261,454). gastroparesis, erectile dysfunction,
D. Neuropathy sudomotor dysfunction, impaired
Specic treatment for the underlying neurovascular function, and,
Recommendations
nerve damage is currently not potentially, autonomic failure in
c All patients should be screened for available, other than improved response to hypoglycemia.
distal symmetric polyneuropathy glycemic control, which may modestly
(DPN) starting at diagnosis of type 2 slow progression in type 2 diabetes Cardiovascular Autonomic Neuropathy.
diabetes and 5 years after the (90) but not reverse neuronal loss. CAN is the most studied and clinically
important form of diabetic autonomic
neuropathy because of its association patients with type 1 diabetes for many require the use of both pharmacological
with mortality risk independent of years (461464). While the evidence is and nonpharmacological measures
other cardiovascular risk factors not as strong for type 2 diabetes as for (e.g., avoiding medications that
(261,397). In early stages CAN may be type 1 diabetes, some studies have aggravate hypotension, using
completely asymptomatic and detected demonstrated a modest slowing of compressive garments over the legs and
by changes in heart rate variability and progression (90,465) without reversal of abdomen).
abnormal cardiovascular reex tests neuronal loss. Several observational Gastroparesis Symptoms. Gastroparesis
(R-R response to deep breathing, studies further suggest that neuropathic symptoms may improve with dietary
standing and Valsalva maneuver). symptoms improve not only with changes and prokinetic agents such as
Advanced disease may be indicated by optimization of control but also with erythromycin. Recently, the European
resting tachycardia (.100 bpm) and the avoidance of extreme blood glucose Medicines Agency (www.ema.europa.
orthostasis (a fall in SBP .20 mmHg or uctuations. eu/docs/en_GB/document_library/
DBP of at least 10 mmHg upon standing
Distal Symmetric Polyneuropathy. DPN Press_release/2013/07/WC500146614.
without an appropriate heart rate
symptoms, and especially neuropathic pdf) decided that risks of extrapyramidal
response). The standard cardiovascular
pain, can be severe, have sudden onset, symptoms with metoclopramide
reex testing, especially the deep-
and are associated with lower quality of outweigh benets. In Europe,
breathing test, is noninvasive, easy to
life, limited mobility, depression, and metoclopramide use is now restricted
perform, reliable, and reproducible and
social dysfunction (466). There is limited to a maximum use of 5 days and is no
has prognostic value. Although some
clinical evidence regarding the most longer indicated for the long-term
societies have developed guidelines for
effective treatments for individual treatment of gastroparesis. Although
screening for CAN, the benets of
patient needs given the wide range of the FDA decision is pending, it is
sophisticated testing beyond risk suggested that metoclopramide be
available medications (467,468). Two
stratication are not clear (460).
drugs have been approved for relief of reserved to only the most severe cases
Gastrointestinal Neuropathies. DPN pain in the U.S.dpregabalin and that are unresponsive to other
Gastrointestinal neuropathies (e.g., duloxetinedbut neither of these therapies. Side effects should be closely
esophageal enteropathy, gastroparesis, affords complete relief, even when used monitored.
constipation, diarrhea, fecal in combination. Venlafaxine, Erectile Dysfunction.Treatments for
incontinence) may involve any section amitriptyline, gabapentin, valproate, erectile dysfunction may include
of the gastrointestinal tract. opioids (morphine sulfate, tramadol, phosphodiesterase type 5 inhibitors,
Gastroparesis should be suspected in and oxycodone controlled-release) may intracorporeal or intraurethral
individuals with erratic glucose control also be effective and could be prostaglandins, vacuum devices, or
or with upper gastrointestinal symptoms considered for treatment of painful penile prostheses. Interventions for
without other identied cause. DPN. Head-to-head treatment other manifestations of autonomic
Evaluation of solid-phase gastric comparisons and studies that include neuropathy are described in the ADA
emptying using double-isotope quality-of-life outcomes are rare, so statement on neuropathy (468). As with
scintigraphy may be done if symptoms treatment decisions must often follow a DPN treatments, these interventions do
are suggestive, but test results often trial-and-error approach. Given the not change the underlying pathology
correlate poorly with symptoms. range of partially effective treatment and natural history of the disease
Constipation is the most common options, a tailored and step-wise process, but may have a positive impact
lower-gastrointestinal symptom but can pharmacological strategy with careful on the quality of life of the patient.
alternate with episodes of diarrhea. attention to relative symptom
Genitourinary Tract Disturbances. improvement, medication adherence,
E. Foot Care
Diabetic autonomic neuropathy is also and medication side effects is
Recommendations
associated with genitourinary tract recommended to achieve pain reduction
and improve quality of life (455). c For all patients with diabetes,
disturbances. In men, diabetic
perform an annual comprehensive
autonomic neuropathy may cause Autonomic Neuropathy. An intensive foot examination to identify risk
erectile dysfunction and/or retrograde multifactorial cardiovascular risk factors predictive of ulcers and
ejaculation. Evaluation of bladder intervention targeting glucose, blood amputations. The foot examination
dysfunction should be performed for pressure, lipids, smoking, and other should include inspection,
individuals with diabetes who have lifestyle factors has been shown to assessment of foot pulses, and
recurrent urinary tract infections, reduce the progression and testing for loss of protective
pyelonephritis, incontinence, or a development of CAN among patients sensation (LOPS) (10-g monolament
palpable bladder. with type 2 diabetes (469). plus testing any one of the following:
Treatment Orthostatic Hypotension.Treatment of vibration using
Glycemic Control.Tight and stable orthostatic hypotension is challenging. 128-Hz tuning fork, pinprick
glycemic control, implemented as early The therapeutic goal is to minimize sensation, ankle reexes, or vibration
as possible has been shown to postural symptoms rather than to perception threshold). B
effectively prevent the development of restore normotension. Most patients c Provide general foot self-care
DPN and autonomic neuropathy in education to all patients with
diabetes. B
c A multidisciplinary approach is examination to identify high-risk (e.g., smoking, hypertension,
recommended for individuals with conditions at least annually. Clinicians hyperlipidemia, or duration of diabetes
foot ulcers and high-risk feet, should ask about history of previous .10 years). Refer patients with
especially those with a history of foot ulceration or amputation, signicant symptoms or a positive ABI
prior ulcer or amputation. B neuropathic or peripheral vascular for further vascular assessment and
c Refer patients who smoke, have LOPS symptoms, impaired vision, tobacco consider exercise, medications, and
and structural abnormalities, or have use, and foot care practices. A general surgical options (471).
history of prior lower-extremity inspection of skin integrity and
complications to foot care specialists musculoskeletal deformities should be Patient Education
for ongoing preventive care and done in a well-lit room. Vascular Patients with diabetes and high-risk
lifelong surveillance. C assessment would include inspection foot conditions should be educated
c Initial screening for peripheral and assessment of pedal pulses. regarding their risk factors and
arterial disease (PAD) should appropriate management. Patients at
include a history for claudication and The neurological exam recommended is
risk should understand the implications
an assessment of the pedal pulses. designed to identify LOPS rather than
of LOPS, the importance of foot
Consider obtaining an ankle-brachial early neuropathy. The clinical
monitoring on a daily basis, the proper
index (ABI), as many patients with examination to identify LOPS is simple
care of the foot, including nail and skin
PAD are asymptomatic. C and requires no expensive equipment.
care, and the selection of appropriate
Refer patients with signicant Five simple clinical tests (use of a 10-g
c footwear. Patients with LOPS should be
claudication or a positive ABI for monolament, vibration testing using a
educated on ways to substitute other
further vascular assessment and 128-Hz tuning fork, tests of pinprick
sensory modalities (hand palpation,
consider exercise, medications, and sensation, ankle reex assessment, and
visual inspection) for surveillance of
surgical options. C testing vibration perception threshold
early foot problems. Patients
with a biothesiometer), each with
understanding of these issues and their
Amputation and foot ulceration, evidence from well-conducted
physical ability to conduct proper foot
consequences of diabetic neuropathy prospective clinical cohort studies, are
surveillance and care should be
and/or PAD, are common and are major considered useful in the diagnosis of
assessed. Patients with visual
causes of morbidity and disability in LOPS in the diabetic foot. The task force
difculties, physical constraints
people with diabetes. Loss of 10-g agreed that any of the ve tests listed
preventing movement, or cognitive
monolament perception and reduced could be used by clinicians to identify
problems that impair their ability to
vibration perception predict foot LOPS, although ideally two of these
assess the condition of the foot and to
ulcers (468). Early recognition and should be regularly performed during
institute appropriate responses will
management of risk factors can prevent the screening examdnormally the 10-g
need other people, such as family
or delay adverse outcomes. monolament and one other test. One
members, to assist in their care.
or more abnormal tests would suggest
The risk of ulcers or amputations is LOPS, while at least two normal tests
increased in people who have the Treatment
(and no abnormal test) would rule out People with neuropathy or evidence of
following risk factors: LOPS. The last test listed, vibration increased plantar pressure (e.g.,
assessment using a biothesiometer or erythema, warmth, callus, or measured
c Previous amputation similar instrument, is widely used in the
c Past foot ulcer history pressure) may be adequately managed
U.S.; however, identication of the with well-tted walking shoes or
c Peripheral neuropathy patient with LOPS can easily be carried
c Foot deformity athletic shoes that cushion the feet and
out without this or other expensive redistribute pressure. Callus can be
c Peripheral vascular disease equipment.
c Visual impairment debrided with a scalpel by a foot care
c Diabetic nephropathy (especially Screening
specialist or other health professional
patients on dialysis) Initial screening for PAD should with experience and training in foot
c Poor glycemic control include a history for claudication and an care. People with bony deformities
c Cigarette smoking assessment of the pedal pulses. A (e.g., hammertoes, prominent
diagnostic ABI should be performed in metatarsal
In 2008, ADA published screening any patient with symptoms of PAD. Due heads, bunions) may need extra-wide
recommendations (470). Clinicians are to the high estimated prevalence of PAD or -deep shoes. People with extreme
encouraged to review this report for in patients with diabetes and the fact bony deformities (e.g., Charcot foot)
further details and practical descriptions that many patients with PAD are who cannot be accommodated with
of how to perform components of the asymptomatic, an ADA consensus commercial therapeutic footwear may
comprehensive foot examination. statement on PAD (471) suggested need custom-molded shoes.
that a screening ABI be performed in Most diabetic foot infections are
Examination patients over 50 years of age and be polymicrobial, with aerobic gram-
All adults with diabetes should considered in patients under 50 years positive cocci (GPC), and especially
undergo a comprehensive foot of age who have other PAD risk factors staphylococci, the most common
causative organisms.
Wounds without evidence of soft tissue in men and women (478). The fracture, although fracture risk was
or bone infection do not require prevalence in general populations with higher in diabetic participants
antibiotic therapy. type 2 diabetes may be up to 23% (479) compared with participants without
Empiric antibiotic therapy can be and in obese participants enrolled in the diabetes for a given T score and age or
narrowly targeted at GPC in many Look AHEAD trial exceeded 80% (480). for a given FRAX score risk (489). It is
acutely infected patients, but those at Treatment of sleep apnea signicantly appropriate to assess fracture history
risk for infection with antibiotic- improves quality of life and blood and risk factors in older patients with
resistant organisms or with chronic, pressure control. The evidence for a diabetes and recommend BMD testing if
previously treated, or severe infections treatment effect on glycemic control is appropriate for the patients age and
require broader spectrum regimens and mixed (481). sex. Prevention strategies are the same
should be referred to specialized care as for the general population. For type 2
Fatty Liver Disease diabetic patients with fracture risk
centers (472). Foot ulcers and wound
Unexplained elevations of hepatic factors, avoiding use of
care may require care by a podiatrist,
transaminase concentrations are thiazolidinediones is warranted.
orthopedic or vascular surgeon, or
signicantly associated with higher BMI,
rehabilitation specialist experienced in Cognitive Impairment
waist circumference, triglycerides, and
the management of individuals with Diabetes is associated with signicantly
fasting insulin, and with lower HDL
diabetes. Guidelines for treatment of increased risk and rate of cognitive
cholesterol. In a prospective analysis,
diabetic foot ulcers have recently been decline and increased risk of dementia
diabetes was signicantly associated
updated (472). (490,491). In a 15-year prospective
with incident nonalcoholic chronic liver
disease and with hepatocellular study of community-dwelling people
VII. ASSESSMENT OF COMMON
carcinoma (482). Interventions that over the age of 60 years, the presence
COMORBID CONDITIONS
improve metabolic abnormalities in of diabetes at baseline signicantly
Recommendation patients with diabetes (weight loss, increased the age- and sex-adjusted
glycemic control, treatment with incidence of all-cause dementia,
c Consider assessing for and addressing
specic drugs for hyperglycemia or Alzheimer disease, and vascular
common comorbid conditions that
dyslipidemia) are also benecial for dementia compared with rates in those
may complicate the management of
fatty liver disease (483). with normal glucose tolerance (492).
diabetes. B
In a substudy of the ACCORD study,
Cancer there were no differences in cognitive
Improved disease prevention and
Diabetes (possibly only type 2 diabetes) outcomes between intensive and
treatment efcacy means that patients
is associated with increased risk of standard glycemic control, although
with diabetes are living longer, often
cancers of the liver, pancreas, there was signicantly less of a
with multiple comorbidities requiring
endometrium, colon/rectum, breast, decrement in total brain volume by MRI
complicated medical regimens (473). In
and bladder (484). The association may in participants in the intensive arm
addition to the commonly appreciated
comorbidities of obesity, hypertension, result from shared risk factors between (493). The effects of hyperglycemia and
and dyslipidemia, diabetes type 2 diabetes and cancer (obesity, age, insulin on the brain are areas of intense
management is often complicated by physical inactivity) but may also be due research interest.
concurrent conditions such as heart to hyperinsulinemia or hyperglycemia Low Testosterone in Men
failure, depression and anxiety, arthritis, (485,486). Patients with diabetes Mean levels of testosterone are lower
and other diseases or conditions at rates should be encouraged to undergo in men with diabetes compared with
higher than those of age-matched recommended age- and sex-appropriate age- matched men without diabetes,
people without diabetes. These cancer screenings and to reduce their but
concurrent conditions present clinical modiable cancer risk factors (obesity, obesity is a major confounder (494).
challenges related to polypharmacy, smoking, physical inactivity). Treatment in asymptomatic men is
prevalent symptoms, and complexity of Fractures controversial. The evidence for effects
care (474477). Age-matched hip fracture risk is of testosterone replacement on
signicantly increased in both type 1 outcomes is mixed, and recent
Depression guidelines suggest that screening and
As discussed in Section V.H, depression, (summary RR 6.3) and type 2 diabetes
(summary RR 1.7) in both sexes (487). treatment of men without symptoms
anxiety, and other mental health are not recommended (495).
symptoms are highly prevalent in Type 1 diabetes is associated with
people with diabetes and are associated osteoporosis, but in type 2 diabetes Periodontal Disease
with worse outcomes. an increased risk of hip fracture is Periodontal disease is more severe, but
seen despite higher bone mineral not necessarily more prevalent, in
Obstructive Sleep Apnea density (BMD) (488). In three large patients with diabetes than in those
Age-adjusted rates of obstructive sleep observational studies of older adults, without (496). Current evidence
apnea, a risk factor for CVD, are femoral neck BMD T score and the suggests that periodontal disease
signicantly higher (4- to 10-fold) with WHO Fracture Risk Algorithm (FRAX) adversely affects diabetes outcomes,
obesity, especially with central obesity, score were associated with hip and although evidence for treatment
nonspine benets is currently lacking (477).
S5050 Position Diabetes Care Volume 37, Supplement 1, January 2014
Statement

Hearing Impairment and family. The balance between adult lower A1C should be balanced against
Hearing impairment, both high supervision and self-care should be the risks of hypoglycemia and the
frequency and low/mid frequency, is dened at the rst interaction and re- developmental burdens of intensive
more common in people with diabetes, evaluated at each clinic visit. This regimens in children and youth. Age-
perhaps due to neuropathy and/or relationship will evolve as the child specic glycemic and A1C goals are
vascular disease. In NHANES analysis, reaches physical, psychological, and presented in Table 14.
hearing impairment was about twice as emotional maturity.
great in people with diabetes compared b. Screening and Management of
with those without, after adjusting for a. Glycemic Control Complications
age and other risk factors for hearing Recommendation
i. Nephropathy
impairment (497). c Consider age when setting glycemic
Recommendations
goals in children and adolescents with
Screening
type 1 diabetes. E
VIII. DIABETES CARE IN SPECIFIC c Annual screening for albumin levels,
POPULATIONS with a random spot urine sample for
Current standards for diabetes
A. Children and Adolescents management reect the need to lower albumin-to-creatinine ratio (ACR),
1. Type 1 Diabetes glucose as safely possible. This should should be considered for the child at
Three-quarters of all cases of type 1 be done with step-wise goals. Special the start of puberty or at age $10
diabetes are diagnosed in individuals consideration should be given to the years, whichever is earlier, once the
,18 years of age. The provider must unique risks of hypoglycemia in young youth has had diabetes for 5 years. B
consider the unique aspects of care children. For young children (,7 years Treatment
and management of children and old), glycemic goals may need to be
adolescents with type 1 diabetes, such c Treatment with an ACE inhibitor,
modied since most at that age have a
as changes in insulin sensitivity related titrated to normalization of albumin
form of hypoglycemic unawareness,
to sexual maturity and physical growth, excretion, should be considered
including immaturity of and a relative
ability to provide self-care, supervision when elevated ACR is subsequently
inability to recognize and respond to
in child care and school, and unique conrmed on two additional
hypoglycemic symptoms. This places
neurological vulnerability to specimens from different days. This
them at greater risk for severe
hypoglycemia and DKA. Attention to should be obtained over a 6-month
hypoglycemia. While it was previously
family dynamics, developmental stages, interval following efforts to improve
thought that young children were at risk
and physiological differences related to glycemic control and normalize blood
for cognitive impairment after episodes
sexual maturity are all essential in pressure for age. E
of severe hypoglycemia, current data
developing and implementing an have not conrmed this (295,499,500).
optimal diabetes regimen. Due to the Recent research demonstrates the
Furthermore, new therapeutic
paucity of clinical research in children, importance of good glycemic and blood
modalities, such as rapid and long-
the recommendations for children and pressue control, especially as diabetes
acting insulin analogs, technological
adolescents are less likely to be based duration increases (506).
advances (e.g., low glucose suspend),
on clinical trial evidence. However, and education may mitigate the ii. Hypertension
expert opinion and a review of available incidence
and relevant experimental data are Recommendations
of severe hypoglycemia (501). In
summarized in the ADA statement on Screening
adolescents, the DCCT demonstrated
care of children and adolescents with that near-normalization of blood c Blood pressure should be measured at
type 1 diabetes (498). glucose levels was more difcult to each routine visit. Children found to
The care of a child or adolescent with achieve compared with adults. have high-normal blood pressure or
type 1 diabetes should be provided by a Nevertheless, the increased frequency hypertension should have blood
multidisciplinary team of specialists of basal-bolus regimens and insulin pressure conrmed on a separate day.
trained in pediatric diabetes pumps in youth from infancy through B
management. At the very least, adolescence has been associated with Treatment
education of the child and family should more children reaching ADA blood
c Initial treatment of high-normal
be provided by health care providers glucose targets (502504) in those
blood pressure (SBP or DBP
trained and experienced in childhood families in which both parents and the
consistently above the 90th
diabetes and sensitive to the challenges child with diabetes participate jointly to
percentile for age, sex, and height)
posed by diabetes in this age-group. It is perform the required diabetes-related
includes dietary intervention and
essential that DSME, MNT, and tasks. Furthermore, studies
exercise, aimed at weight control
psychosocial support be provided at documenting neurocognitive imaging
and increased physical activity, if
diagnosis and regularly thereafter by differences of hyperglycemia in children
appropriate. If target blood pressure
individuals experienced with the provide another compelling motivation
is not reached with 36 months
educational, nutritional, behavioral, and for achieving glycemic targets (505).
of lifestyle intervention,
emotional needs of the growing child In selecting glycemic goals, the long- pharmacological treatment should
term health benets of achieving a be considered. E
Table 14Plasma blood glucose and A1C goals for type 1 diabetes by age-group
Plasma blood glucose goal range
(mg/dL)
Values by age (years) Before meals Bedtime/overnight A1C Rationale
Toddlers and preschoolers (06) 100180 110200 ,8.5% c Vulnerability to hypoglycemia
c Insulin sensitivity
c Unpredictability in dietary intake and physical activity
c A lower goal (,8.0%) is reasonable if it can be achieved
without excessive hypoglycemia
School age (612) 90180 100180 ,8% c Vulnerability of hypoglycemia
c A lower goal (,7.5%) is reasonable if it can be achieved
without excessive hypoglycemia
Adolescents and young adults (1319) 90130 90150 ,7.5% c A lower goal (,7.0%) is reasonable if it can be achieved
without excessive hypoglycemia
Key concepts in setting glycemic goals:
c Goals should be individualized and lower goals may be reasonable based on benet-risk assessment.
c Blood glucose goals should be modied in children with frequent hypoglycemia or hypoglycemia unawareness.
c Postprandial blood glucose values should be measured when there is a discrepancy between preprandial blood glucose values and A1C levels
and to help assess glycemia in those on basal-bolus regimens.

c Pharmacological treatment of cardiovascular event before age 55 (2.6 mmol/L). E


hypertension (SBP or DBP years, or if family history is unknown,
consistently above the 95th then consider obtaining a fasting lipid
percentile for age, sex, and height or prole in children .2 years of age
consistently .130/80 mmHg, if 95% soon after the diagnosis (after glucose
exceeds that value) should be control has been established). If
considered as soon as the diagnosis is family history is not of concern, then
conrmed. E consider the rst lipid screening at
c ACE inhibitors should be considered puberty ($10 years). For children
for the initial pharmacological diagnosed with diabetes at or after
treatment of hypertension, following puberty, consider obtaining a fasting
appropriate reproductive counseling lipid prole soon after the diagnosis
due to its potential teratogenic (after glucose control has been
effects. E established). E
c The goal of treatment is blood c For both age-groups, if lipids are
pressure consistently ,130/80 or abnormal, annual monitoring is
below the 90th percentile for reasonable. If LDL cholesterol values
age, sex, and height, whichever is are within the accepted risk levels
lower. E (,100 mg/dL [2.6 mmol/L]), a lipid
prole repeated every 5 years is
Blood pressure measurements should reasonable. E
be determined correctly, using the
Treatment
appropriate size cuff, and with the child
seated and relaxed. Hypertension c Initial therapy may consist of
should be conrmed on at least three optimization of glucose control and
separate days. Normal blood pressure MNT using a Step 2 AHA diet aimed
levels for age, sex, and height at a decrease in the amount of
and appropriate methods for saturated fat in the diet. E
determinations are available online at c After the age of 10 years, the addition
www.nhlbi.nih.gov/health/prof/heart/ of a statin in patients who, after MNT
hbp/hbp_ped.pdf. and lifestyle changes, have LDL
cholesterol .160 mg/dL (4.1 mmol/L)
iii. Dyslipidemia or LDL cholesterol .130 mg/dL (3.4
Recommendations mmol/L) and one or more CVD risk
Screening factors is reasonable. E
c If there is a family history of c The goal of therapy is an LDL
hypercholesterolemia or a cholesterol value ,100 mg/dL
Children diagnosed with type 1
diabetes have a high risk of early
subclinical (507,508) and clinical
(509) CVD. Although intervention
data are lacking, the AHA
categorizes children with type 1
diabetes in the highest tier for
cardiovascular risk and
recommends
both lifestyle and
pharmacological treatment for
those with elevated LDL
cholesterol levels (510,511).
Initial therapy should be with a
Step 2 AHA diet, which restricts
saturated fat to 7% of total
calories and restricts dietary
cholesterol to 200 mg/day. Data
from randomized clinical trials in
children as young as 7 months of
age indicate that this diet is safe
and does not interfere with
normal growth and development
(512,513). Abnormal results from
a
random lipid panel should be
conrmed with a fasting lipid
panel. Evidence has shown that
improved glucose control
correlates with a more favorable
lipid
prole. However, improved
glycemic control alone will not
reverse signicant dyslipidemia
(514). Neither long-term safety
nor cardiovascular outcome
efcacy of statin therapy has
been established for children.
However, studies have shown
short-term safety equivalent to
that seen in adults and efcacy in
lowering LDL cholesterol
levels, improving endothelial
function and causing regression
of carotid
intimal thickening (515517). Statins
are not approved for use under
the age of 10 years, and statin
treatment
should generally not be used in disease in asymptomatic children with vi. Hypothyroidism
children with type 1 diabetes prior positive antibodies. E Recommendations
to this age. For postpubertal girls, c Children with biopsy-conrmed
issues of pregnancy prevention are c Consider screening children with type
celiac disease should be placed on a
paramount, since statins are category X 1 diabetes for antithyroid peroxidase
gluten-free diet and have
in pregnancy (see Section VIII.B for and antithyroglobulin antibodies
consultation with a dietitian
more information). soon after diagnosis. E
experienced in managing both
c Measuring thyroid-stimulating
iv. Retinopathy diabetes and celiac disease. B
hormone (TSH) concentrations soon
Recommendations after diagnosis of type 1 diabetes,
c An initial dilated and comprehensive Celiac disease is an immune-mediated after metabolic control has been
eye examination should be disorder that occurs with increased established, is reasonable. If normal,
considered for the child at the start of frequency in patients with type 1 consider rechecking every 12 years,
puberty or at age $10 years, diabetes (116% of individuals especially if the patient develops
whichever is earlier, once the youth compared with 0.31% in the general symptoms of thyroid dysfunction,
has had diabetes for 35 years. B population) (519,520). Symptoms of thyromegaly, an abnormal growth
c After the initial examination, annual celiac disease include diarrhea, weight rate, or unusual glycemic variation. E
routine follow-up is generally loss or poor weight gain, growth
recommended. Less frequent failure, abdominal pain, chronic Autoimmune thyroid disease is the most
examinations may be acceptable on fatigue, malnutrition due to common autoimmune disorder
the advice of an eye care malabsorption, and other associated with diabetes, occurring in
professional. E gastrointestinal problems, and 1730% of patients with type 1 diabetes
unexplained hypoglycemia or erratic (524). About one-quarter of type 1
Although retinopathy (like albuminuria) blood glucose concentrations. diabetic children have thyroid
most commonly occurs after the onset autoantibodies at the time of diagnosis
of puberty and after 510 years of Screening (525), and the presence of thyroid
diabetes duration (518), it has been Screening for celiac disease includes autoantibodies is predictive of thyroid
reported in prepubertal children and measuring serum levels of tissue dysfunction, generally hypothyroidism
transglutaminase or antiendomysial but less commonly hyperthyroidism
with diabetes duration of only 12
antibodies, then small-bowel biopsy in (526). Subclinical hypothyroidism may
years. Referrals should be made to eye
antibody-positive children. European be associated with increased risk of
care professionals with expertise in
guidelines on screening for celiac symptomatic hypoglycemia (527) and
diabetic retinopathy, an understanding
disease in children (not specic to with reduced linear growth (528).
of retinopathy risk in the pediatric
children with type 1 diabetes) suggested Hyperthyroidism alters glucose
population, and experience in
that biopsy may not be necessary in metabolism, potentially resulting in
counseling the pediatric patient and
symptomatic children with positive deterioration of metabolic control.
family on the importance of early
antibodies, as long as further testing
prevention/intervention. c. Self-Management
such as genetic or HLA testing was
v. Celiac Disease supportive, but that asymptomatic at- No matter how sound the medical
Recommendations risk children should have biopsies (521). regimen, it can only be as good as the
One small study that included children ability of the family and/or individual to
c Consider screening children with type
with and without type 1 diabetes implement it. Family involvement
1 diabetes for celiac disease by remains an important component of
measuring IgA antitissue suggested that antibody- positive but
biopsy-negative children were similar optimal diabetes management
transglutaminase or antiendomysial throughout childhood and adolescence.
antibodies, with documentation of clinically to those who were biopsy-
positive. Health care providers who care for
normal total serum IgA levels, soon children and adolescents, therefore,
after the diagnosis of diabetes. E Treatment must be capable of evaluating the
c Testing should be considered in Biopsy-negative children had benets educational, behavioral, emotional, and
children with a positive family history from a gluten-free diet, but worsening psychosocial factors that impact
of celiac disease, growth failure, on a usual diet (522). This was a small implementation of a treatment plan and
failure to gain weight, weight loss, study, and children with type 1 diabetes must work with the individual and
diarrhea, atulence, abdominal pain, already follow a careful diet. However, family to overcome barriers or redene
or signs of malabsorption or in it is difcult to advocate for not goals as appropriate.
children with frequent unexplained conrming the diagnosis by biopsy
hypoglycemia or deterioration in before recommending a lifelong gluten- d. School and Day Care
glycemic control. E free diet, especially in asymptomatic Since a large portion of a childs day is
c Consider referral to a gastroenterologist children. In symptomatic children with spent in school, close communication
for evaluation with possible type 1 diabetes and celiac disease, with and cooperation of school or day
endoscopy and biopsy for gluten-free diets reduce symptoms and care personnel is essential for optimal
conrmation of celiac rates of hypoglycemia (523).
diabetes management, safety, and specic recommendations, is found in (32) provides guidance on the
maximal academic opportunities. See the ADA position statement Diabetes prevention, screening, and treatment of
the ADA position statement Diabetes Care for Emerging Adults: type 2 diabetes and its comorbidities in
Care in the School and Day Care Recommendations for Transition From young people.
Setting (529) for further discussion. Pediatric to Adult Diabetes Care 3. Monogenic Diabetes Syndromes
e. Transition From Pediatric to Adult Systems (532). Monogenic forms of diabetes
Care
The National Diabetes Education (neonatal diabetes or maturity-onset
Recommendations Program (NDEP) has materials available diabetes of the young) represent a
c As teens transition into emerging to facilitate the transition process small fraction of children with diabetes
adulthood, health care providers (http://ndep.nih.gov/transitions/), and (,5%), but readily available
and families must recognize their The Endocrine Society in collaboration commercial genetic testing now
many vulnerabilities B and with ADA and other organizations has enables a true genetic diagnosis with
prepare the developing teen, developed transition tools for clinicians increasing frequency. It is important
beginning in early to mid and youth/families (http://www.endo- to correctly diagnose one of the
adolescence and at least 1 year prior society.org/clinicalpractice/ monogenic forms of diabetes, as these
to the transition. E transition_of_care.cfm). children may be incorrectly diagnosed
c Both pediatricians and adult health 2. Type 2 Diabetes with type 1 or type 2 diabetes, leading
care providers should assist in The CDC recently published projections to suboptimal treatment regimens and
providing support and links to for type 2 diabetes prevalence using the delays in diagnosing other family
resources for the teen and emerging SEARCH database. Assuming a 2.3% members.
adult. B annual increase, the prevalence of type The diagnosis of monogenic diabetes
2 diabetes in those under 20 years of should be considered in children with
Care and close supervision of diabetes age will quadruple in 40 years (31,38). the following situations:
management is increasingly shifted Given the current obesity epidemic,
from parents and other older adults distinguishing between type 1 and type c Diabetes diagnosed within the rst
throughout childhood and adolescence; 2 diabetes in children can be difcult. six months of life.
however, the shift from pediatrics to Autoantigens and ketosis may be c Strong family history of diabetes but
adult health care providers often occurs present in a substantial number of without typical features of type 2
very abruptly as the older teen enters patients with features of type 2 diabetes (nonobese, low-risk ethnic
the next developmental stage referred diabetes (including obesity and group).
to as emerging adulthood (530), acanthosis nigricans). Such a distinction c Mild fasting hyperglycemia (100150
a critical period for young people who at diagnosis is critical since treatment mg/dL [5.58.5 mmol]), especially if
have diabetes. During this period of regimens, educational approaches, young and nonobese.
major life transitions, youth begin to dietary counsel, and outcomes will c Diabetes but with negative auto-
move out of their parents home and differ markedly between the two antibodies without signs of obesity or
must become more fully responsible for diagnoses. insulin resistance.
their diabetes care including the many
aspects of self-management, making Type 2 diabetes has a signicant
incidence of comorbidities already A recent international consensus
medical appointments, and nancing document discusses in further detail the
health care once they are no longer present at the time of diagnosis (535). It
is recommended that blood pressure diagnosis and management of children
covered under their parents health with monogenic forms of diabetes
insurance (531,532). In addition to measurement, a fasting lipid prole,
assessment for albumin excretion, and (536).
lapses in health care, this is also a
period of deterioration in glycemic dilated eye examination be performed
control, increased occurrence of acute at diagnosis. Thereafter, screening B. Preconception Care
complications, psycho-social- guidelines and treatment Recommendations
emotional-behavioral issues, and recommendations for hypertension, c A1C levels should be as close to
emergence of chronic complications dyslipidemia, albumin excretion, and normal as possible (,7%) in an
(531534). retinopathy in youth with type 2 individual patient before conception
diabetes are similar to those for youth is attempted. B
Though scientic evidence continues to with type 1 diabetes. Additional c Starting at puberty, preconception
be limited, it is clear that early and problems that may need to be counseling should be incorporated in
ongoing attention be given to addressed include polycystic ovarian the routine diabetes clinic visit for all
comprehensive and coordinated disease and the various comorbidities women of childbearing potential. B
planning for seamless transition of all associated with pediatric obesity such c Women with diabetes who are
youth from pediatric to adult health as sleep apnea, hepatic steatosis, contemplating pregnancy should be
care (531,532). A comprehensive orthopedic complications, and evaluated and, if indicated, treated
discussion regarding the challenges psychosocial concerns. The ADA for diabetic retinopathy, nephropathy,
faced during this period, including consensus statement on this subject neuropathy, and CVD. B
c Medications used by such women participated in preconception care absolutely contraindicated during
should be evaluated prior to (range 1.01.7% of infants) was much pregnancy. Statins are category X
conception, since drugs commonly lower than the incidence in women who (contraindicated for use in pregnancy)
used to treat diabetes and its did not participate (range 1.410.9% of and should be discontinued before
complications may be infants) (104). One limitation of these conception, as should ACE inhibitors
contraindicated or not recommended studies is that participation in (539). ARBs are category C (risk cannot
in pregnancy, including statins, ACE preconception care was self-selected be ruled out) in the rst trimester but
inhibitors, ARBs, and most noninsulin rather than randomized. Thus, it is category D (positive evidence of risk) in
therapies. E impossible to be certain that the lower later pregnancy and should generally be
c Since many pregnancies are malformation rates resulted fully from discontinued before pregnancy. Since
unplanned, consider the potential improved diabetes care. Nonetheless, many pregnancies are unplanned,
risks and benets of medications that the evidence supports the concept that health care professionals caring for any
are contraindicated in pregnancy in malformations can be reduced or woman of childbearing potential should
all women of childbearing potential prevented by careful management of consider the potential risks and benets
and counsel women using such diabetes before pregnancy (537). of medications that are contraindicated
medications accordingly. E in pregnancy. Women using
Planned pregnancies greatly facilitate
preconception diabetes care. medications such as statins or ACE
Major congenital malformations remain inhibitors need ongoing family planning
the leading cause of mortality and Unfortunately, nearly two-thirds of
pregnancies in women with diabetes counseling. Among the oral antidiabetic
serious morbidity in infants of mothers agents, metformin and acarbose are
with type 1 and type 2 diabetes. are unplanned, potentially leading to
malformations in infants of diabetic classied as category B (no evidence of
Observational studies indicate that the risk in humans) and all others as
risk of malformations increases mothers. To minimize the occurrence of
these devastating malformations, category C. Potential risks and benets
continuously with increasing maternal of oral antidiabetic agents in the
glycemia during the rst 68 weeks of beginning at the onset of puberty or at
diagnosis, all women with diabetes with preconception period must be carefully
gestation, as dened by rst-trimester weighed, recognizing that data are
A1C concentrations. There is no childbearing potential should receive
1) education about the risk of insufcient to establish the safety of
threshold for A1C values below which these agents in pregnancy.
risk disappears entirely. However, malformations associated with
malformation rates above the 12% unplanned pregnancies and poor For further discussion of preconception
background rate of nondiabetic metabolic control and 2) use of care, see the ADA consensus statement
pregnancies appear to be limited to effective contraception at all times, on preexisting diabetes and pregnancy
pregnancies in which rst-trimester A1C unless the patient has good metabolic (104) and the position statement (540).
concentrations are .1% above the control and is actively trying to
normal range for a nondiabetic conceive. A recent study showed that C. Older Adults
pregnant woman. preconception counseling using simple Recommendations
educational c Older adults who are functional,
Preconception Care tools enabled adolescent girls to make cognitively intact, and have
Preconception care of diabetes appears well-informed decisions lasting up to 9 signicant life expectancy should
to reduce the risk of congenital months (538). receive diabetes care with goals
malformations. Five nonrandomized Women contemplating pregnancy need similar to those developed for
studies compared rates of major to be seen frequently by a younger adults. E
malformations in infants between multidisciplinary team experienced in c Glycemic goals for some older adults
women who participated in diabetes management both before and might reasonably be relaxed, using
preconception diabetes care programs during pregnancy. The goals of individual criteria, but hyperglycemia
and women who initiated intensive preconception care are to 1) involve and leading to symptoms or risk of acute
diabetes management after they were empower the patient on diabetes hyperglycemic complications should
already pregnant. The preconception management, 2) achieve the lowest A1C be avoided in all patients. E
care programs were multidisciplinary test results possible without excessive c Other cardiovascular risk factors
and designed to train patients in hypoglycemia, 3) assure effective should be treated in older adults with
diabetes self-management with diet, contraception until stable and consideration of the time frame of
intensied insulin therapy, and SMBG. acceptable glycemia is achieved, and 4) benet and the individual patient.
Goals were set to achieve normal blood identify, evaluate, and treat long-term Treatment of hypertension is
glucose concentrations, and .80% of diabetes complications such as indicated in virtually all older adults,
subjects achieved normal A1C retinopathy, nephropathy, neuropathy, and lipid and aspirin therapy may
concentrations before they became hypertension, and CHD (104). benet those with life expectancy at
pregnant. In all ve studies, the least equal to the time frame of
incidence of major congenital Drugs Contraindicated in Pregnancy primary or secondary prevention
malformations in women who Drugs commonly used in the diabetes trials. E
treatment may be relatively or
c Screening for diabetes complications adults with diabetes is complicated by expected to live long enough to reap the
should be individualized in older their clinical and functional benets of long-term intensive diabetes
adults, but particular attention heterogeneity. Some older individuals management, who have good cognitive
should be paid to complications developed diabetes years earlier and and functional function, and who
that would lead to functional may have signicant complications; choose to do so via shared decision
impairment. E others who are newly diagnosed may making may be treated using
have had years of undiagnosed diabetes therapeutic interventions and goals
Diabetes is an important health with resultant complications or may similar to those for younger adults with
condition for the aging population; at have truly recent-onset disease and few diabetes. As with all patients, DSME and
least 20% of patients over the age of 65 or no complications. Some older adults ongoing DSMS are vital components of
years have diabetes, and this number with diabetes are frail and have other diabetes care for older adults and their
can be expected to grow rapidly in the underlying chronic conditions, caregivers.
coming decades. Older individuals with substantial diabetes-related
diabetes have higher rates of premature For patients with advanced diabetes
comorbidity, or limited physical or complications, life-limiting comorbid
death, functional disability, and cognitive functioning. Other older
coexisting illnesses such as illness, or substantial cognitive or
individuals with diabetes have little functional impairment, it is reasonable
hypertension, CHD, and stroke than comorbidity and are active. Life
those without diabetes. Older adults to set less intensive glycemic target
expectancies are highly variable for this goals. These patients are less likely to
with diabetes are also at greater risk population, but often longer than benet from reducing the risk of
than other older adults for several clinicians realize. Providers caring for microvascular complications and more
common geriatric syndromes, such as older adults with diabetes must take this likely to suffer serious adverse effects
polypharmacy, depression, cognitive heterogeneity into consideration when from hypoglycemia. However, patients
impairment, urinary incontinence, setting and prioritizing treatment goals with poorly controlled diabetes may be
injurious falls, and persistent pain. (Table 15). subject to acute complications of
A consensus report on diabetes There are few long-term studies in diabetes, including dehydration, poor
and older adults (541) inuenced older adults demonstrating the benets wound healing, and hyperglycemic
the following discussion and of intensive glycemic, blood pressure, hyperosmolar coma. Glycemic goals at a
recommendations. The care of older and lipid control. Patients who can be minimum should avoid these
consequences.

Table 15Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults
with diabetes
Fasting or Bedtime Blood
Patient characteristics/ Reasonable preprandial glucose pressure
hea lth sta tus Rat io nal e A 1C g oal g lu co se (m g/d L) (m g/d L) (m mH g ) Li
pi ds
Healthy (few coexisting Longer remaining life ,7.5% 90130 90150 ,140/80 Statin unless
chronic illnesses, intact expectancy contraindicated or not
cognitive and functional tolerated
status)
Complex/intermediate Intermediate remaining ,8.0% 90150 100180 ,140/80 Statin unless
(multiple coexisting life expectancy, high contraindicated or not
chronic illnesses* or 21 treatment burden, tolerated
instrumental ADL hypoglycemia
impairments or mild-to- vulnerability, fall risk
moderate cognitive
impairment)
Very complex/poor health Limited remaining life ,8.5% 100180 110200 ,150/90 Consider likelihood of
(long-term care or end- expectancy makes benet with statin
stage chronic illnesses** benet uncertain (secondary prevention
or moderate-to-severe more so than primary)
cognitive impairment or
21 ADL dependencies)
This represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with
diabetes. The patient characteristic categories are general concepts. Not every patient will clearly fall into a particular category. Consideration of
patient/ caregiver preferences is an important aspect of treatment individualization. Additionally, a patients health status and preferences may
change over time. ADL, activities of daily living. A lower goal may be set for an individual if achievable without recurrent or severe
hypoglycemia or undue treatment burden. *Coexisting chronic illnesses are conditions serious enough to require medications or lifestyle
management and may include arthritis, cancer, CHF, depression, emphysema, falls, hypertension, incontinence, stage 3 or worse CKD, MI, and
stroke. By multiple, we mean at least three, but many patients may have ve or more (132). **The presence of a single end-stage chronic illness
such as stage 3-4 CHF or oxygen- dependent lung disease, CKD requiring dialysis, or uncontrolled metastatic cancer may cause signicant
symptoms or impairment of functional status and signicantly reduce life expectancy. A1C of 8.5% equates to an eAG of ;200 mg/dL. Looser
glycemic targets than this may expose patients to acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar syndrome, and poor
wound healing.
Although hyperglycemia control may be glycemic goals. A c Annual monitoring for
important in older individuals with complications of diabetes is
diabetes, greater reductions in morbidity recommended,
and mortality may result from control of beginning 5 years after the
other cardiovascular risk factors rather diagnosis of CFRD. E
than from tight glycemic control alone.
There is strong evidence from clinical CFRD is the most common
trials of the value of treating comorbidity in persons with cystic
hypertension in the elderly (542,543). brosis, occurring in about 20% of
There is less evidence for lipid- lowering adolescents and 40
and aspirin therapy, although the benets 50% of adults. Diabetes in this
of these interventions for primary and population is associated with worse
secondary prevention are likely to apply nutritional status, more severe
to older adults whose life expectancies inammatory lung disease, and
equal or exceed the time frames seen in greater mortality from respiratory
clinical trials. failure.
Special care is required in prescribing Insulin insufciency related to partial
and monitoring pharmacological brotic destruction of the islet mass is
therapy in older adults. Costs may be a the primary defect in CFRD.
signicant factor, especially since Genetically determined function of the
older adults tend to be on many remaining
medications. Metformin may be b-cells and insulin resistance
contraindicated because of renal associated with infection and
insufciency or signicant heart failure. inammation may also play a role.
Thiazolidinediones, if used at all, should Encouraging data suggest that
be used very cautiously in those with, improved screening (544,545) and
or at risk for, CHF, and have also been aggressive insulin therapy have
associated with fractures. Sulfonylureas, narrowed the gap in mortality
other insulin secretagogues, and insulin between cystic brosis patients with
can cause hypoglycemia. Insulin use and without diabetes, and have
requires that patients or caregivers have eliminated the sex difference in
good visual and motor skills and mortality (546). Recent trials
cognitive ability. DPP-4 inhibitors have comparing insulin with oral repaglinide
few side effects, but their costs may be showed no signicant difference
a barrier to some older patients; the between the
latter is also the case for GLP-1 groups. Insulin remains the most
agonists. widely used therapy for CFRD (547).

Screening for diabetes complications in Recommendations for the clinical


older adults also should be management of CFRD can be found
individualized. Particular attention in the recent ADA position statement
should be paid to complications that can on this topic (548).
develop over short periods of time and/
or that would signicantly impair IX. DIABETES CARE IN
functional status, such as visual and SPECIFIC SETTINGS
lower-extremity complications. A. Diabetes Care in the Hospital
Recommendations
D. Cystic FibrosisRelated Diabetes
c Diabetes discharge planning should
Recommendations
start at hospital admission, and
c Annual screening for CFRD with OGTT clear diabetes management
should begin by age 10 years in all instructions should be provided at
patients with cystic brosis who do discharge. E
not have CFRD. B A1C as a screening c The sole use of sliding scale insulin
test for CFRD is not recommended. B in the inpatient hospital setting is
c During a period of stable health, the discouraged. E
diagnosis of CFRD can be made in c All patients with diabetes admitted
cystic brosis patients according to to the hospital should have their
usual glucose criteria. E diabetes clearly identied in the
c Patients with CFRD should be treated medical record. E
with insulin to attain individualized
c All patients with diabetes should have an order treatment of persistent
for blood glucose monitoring, with results hyperglycemia starting at a
available to all members of the health care threshold of no greater than 180
team. E mg/dL (10 mmol/L). Once insulin
c Goals for blood glucose levels: therapy is started, a glucose range
Critically ill patients: Insulin therapy of 140180 mg/dL (7.810 mmol/L)
should be initiated for is recommended for the majority of
critically ill patients. A
More stringent goals, such as 110
140 mg/dL (6.17.8 mmol/L) may
be appropriate for selected
patients, as long as this can be
achieved without signicant
hypoglycemia. C
Critically ill patients require an
intravenous insulin protocol that
has demonstrated efcacy and
safety in achieving the desired
glucose range without increasing
risk for severe hypoglycemia. E
Noncritically ill patients: There is
no clear evidence for specic blood
glucose goals. If treated with
insulin, the premeal blood glucose
targets generally ,140
mg/dL (7.8 mmol/L) with random
blood glucose ,180 mg/dL (10.0
mmol/L) are reasonable,
provided these targets can be
safely achieved. More stringent
targets may be appropriate in
stable patients with previous
tight glycemic control. Less
stringent targets may be
appropriate in those with severe
comorbidities. E
Scheduled subcutaneous insulin
with basal, nutritional, and
correctional components is the
preferred method for achieving
and maintaining glucose control in
noncritically ill patients. C
Glucose monitoring should be
initiated in any patient not known
to be diabetic who receives therapy
associated with high risk
for hyperglycemia, including
high-dose glucocorticoid
therapy, initiation of enteral or
parenteral nutrition, or other
medications such as octreotide or
immunosuppressive medications. B
If hyperglycemia is documented
and persistent, consider treating
such patients to the same glycemic
goals as in patients with known
diabetes. E
A hypoglycemia management
protocol should be adopted and
implemented by each hospital or diabetes) to poor outcomes. Cohort be necessary to target blood glucose values
hospital system. A plan for studies as well as a few early RCTs
preventing and treating suggested that intensive treatment of
hypoglycemia should be hyperglycemia improved hospital
established for each patient. outcomes (549551). In general, these
Episodes of hypoglycemia in the studies were heterogeneous in terms of
hospital should be documented in patient population, blood glucose
the medical record and tracked. E targets and insulin protocols used,
Consider obtaining an A1C in provision of nutritional support and the
patients with diabetes admitted to proportion of patients receiving insulin,
the hospital if the result of testing which limits the ability to make
in the previous 23 months is not meaningful comparisons among them.
available. E Trials in critically ill patients have failed
Consider obtaining an A1C in to show a signicant improvement in
patients with risk factors for mortality with intensive glycemic
undiagnosed diabetes who exhibit control (552,553) or have even shown
hyperglycemia in the hospital. E increased mortality risk (554).
Patients with hyperglycemia in the Moreover, these recent RCTs have
hospital who do not have a prior highlighted the risk of severe
diagnosis of diabetes should have hypoglycemia resulting from such
appropriate plans for follow-up efforts (552557).
testing and care documented at The largest study to date, NICE-
discharge. E SUGAR, a multicenter, multinational
RCT, compared the effect of intensive
Hyperglycemia in the hospital can glycemic control (target 81108
represent previously known diabetes, mg/dL, mean blood glucose attained
previously undiagnosed diabetes, or 115 mg/dL) to standard glycemic
hospital-related hyperglycemia (fasting control (target 144180 mg/dL, mean
blood glucose $126 mg/dL or random blood glucose attained 144 mg/dL) on
blood glucose $200 mg/dL occurring outcomes among 6,104 critically ill
during the hospitalization that reverts to participants, almost all of whom
normal after hospital discharge). The required mechanical ventilation (554).
difculty distinguishing between the Ninety-day mortality was signicantly
second and third categories during the higher in the intensive versus the
hospitalization may be overcome by conventional group in both surgical and
measuring an A1C in undiagnosed medical patients, as was mortality from
patients with hyperglycemia, as long as cardiovascular causes. Severe
conditions interfering with A1C utility hypoglycemia was also more common
(hemolysis, blood transfusion) have not in the intensively treated group (6.8%
occurred. Hyperglycemia management vs. 0.5%; P , 0.001). The precise
in the hospital has been considered reason for the increased mortality in
secondary in importance to the the
condition that prompted admission. tightly controlled group is unknown.
However, a body of literature now The study results lie in stark contrast
supports targeted glucose control in the to a 2001 single-center study that
hospital setting for potential improved reported a 42% relative reduction
clinical outcomes. Hyperglycemia in the in intensive care unit (ICU) mortality in
hospital may result from stress, critically ill surgical patients treated
decompensation of type 1 or type 2 or to a target blood glucose of 80110
other forms of diabetes, and/or may be mg/dL (549). Importantly, the control
iatrogenic due to withholding of group in NICE-SUGAR had reasonably
antihyperglycemic medications or good blood glucose management,
administration of hyperglycemia- maintained at a mean glucose of 144
provoking agents such as mg/dL, only
glucocorticoids or vasopressors. 29 mg/dL above the intensively
There is substantial observational managed patients. This studys ndings
evidence linking hyperglycemia in do not disprove the notion that glycemic
hospitalized patients (with or without control in the ICU is important. However,
they do strongly suggest that it may not
,140 mg/dL and that a highly normal individuals (559). Both
stringent target of ,110 mg/dL hyper-
may actually be dangerous. and hypoglycemia among
In a meta-analysis of 26 trials (N 5 inpatients are associated with
13,567), which included the NICE- adverse short- and
SUGAR data, the pooled RR of long-term outcomes. Early
death with intensive insulin recognition and treatment of
therapy was 0.93 as compared mild to moderate
with conventional therapy (95% CI hypoglycemia (4069 mg/dL
0.831.04) (557). Approximately [2.23.8 mmol/L]) can prevent
half of these trials reported deterioration to a more severe
hypoglycemia, with a pooled episode with potential adverse
RR of intensive therapy of 6.0 sequelae (560).
(95% CI 4.5
8.0). The specic ICU setting
inuenced the ndings, with
patients in surgical ICUs appearing
to benet from intensive insulin
therapy (RR 0.63 [95% CI 0.44
0.91]), while those in other
medical and mixed critical care
settings did not. It was concluded
that, overall, intensive insulin
therapy increased the risk of
hypoglycemia but provided no
overall
benet on mortality in the
critically ill, although a possible
mortality benet to patients
admitted to the surgical ICU was
suggested.
1. Glycemic Targets in Hospitalized
Patients

Denition of Glucose
Abnormalities in the Hospital
Setting
Hyperglycemia in the hospital has been
dened as any blood glucose .140 mg/
dL (7.8 mmol/L). Levels that are
signicantly and persistently
above this may require treatment
in hospitalized patients. A1C
values .6.5% suggest, in
undiagnosed patients, that
diabetes
preceded hospitalization (558).
Hypoglycemia has been dened
as any blood glucose ,70 mg/dL
(3.9 mmol/L). This is the standard
denition in
outpatients and correlates
with the initial threshold for
the release of
counter-regulatory hormones.
Severe hypoglycemia in
hospitalized patients
has been dened by many as ,
40 mg/ dL (2.2 mmol/L), although
this is lower than the ;50 mg/dL
(2.8 mmol/L) level at which
cognitive impairment begins in
Critically Ill Patients comorbidities, as well as in those in feedings and with high dose
Based on the weight of the available patient-care settings where frequent glucocorticoid therapy (560).
evidence, for the majority of critically ill glucose monitoring or close nursing
patients in the ICU setting, insulin There are no data on the safety and
supervision is not feasible. efcacy of oral agents and injectable
infusion should be used to control
hyperglycemia, with a starting threshold Clinical judgment, combined with noninsulin therapies such as GLP-1
of no higher than 180 mg/dL (10.0 ongoing assessment of the patients analogs and pramlintide in the hospital.
mmol/L). Once intravenous insulin is clinical status, including changes in the They appear to have a limited role in
started, the glucose level should be trajectory of glucose measures, the hyperglycemia management in
maintained between 140 and 180 severity of illness, nutritional status, or conjunction with acute illness.
mg/dL (7.8 and 10.0 mmol/L). Greater concomitant medications that might Continuation of these agents may be
benet maybe realized at the lower end affect glucose levels (e.g., steroids, appropriate in selected stable patients
of this range. Although strong evidence octreotide) must be incorporated into who are expected to consume meals at
is lacking, lower glucose targets may be the day-to-day decisions regarding regular intervals. They may be initiated
appropriate in selected patients. One insulin dosing (560). or resumed in anticipation of discharge
small study suggested that ICU patients once the patient is clinically stable.
treated to targets of 120140 had less
2. Antihyperglycemic Agents in Specic caution is required with
negative nitrogen balance than those
Hospitalized Patients metformin, due to the possibility that a
In most clinical situations in the hospital, contraindication may develop during
treated to higher targets (561).
insulin therapy is the preferred method the hospitalization, such as renal
However, targets ,110 mg/dL
of glycemic control (560). In the ICU, insufciency, unstable hemodynamic
(6.1 mmol/L) are not recommended.
intravenous infusion is the preferred status, or need for an imaging study that
Insulin infusion protocols with
route of insulin administration. When requires a radiocontrast dye.
demonstrated safety and efcacy,
the patient is transitioned off
resulting in low rates of hypoglycemia, 3. Preventing Hypoglycemia
intravenous insulin to subcutaneous
are highly recommended (560). Patients with or without diabetes may
therapy, precautions should be taken to
prevent hyperglycemia escape experience hypoglycemia in the hospital
Noncritically Ill Patients
(564,565). Outside of critical care units, setting in association with altered
With no prospective RCT data to inform
scheduled subcutaneous insulin that nutritional state, heart failure, renal or
specic glycemic targets in non
delivers basal, nutritional, and liver disease, malignancy, infection, or
critically ill patients, recommendations
correctional (supplemental) sepsis. Additional triggering events
are based on clinical experience and
components is recommended. Typical leading to iatrogenic hypoglycemia
judgment (562). For the majority of
dosing schemes are based on body include sudden reduction of
noncritically ill patients treated with
weight, with some evidence that corticosteroid dose, altered ability of
insulin, premeal glucose targets should
patients with renal insufciency should the patient to report symptoms,
generally be ,140 mg/dL (7.8 mmol/L)
be treated with lower doses (566). reduced oral intake, emesis, new NPO
with random blood glucose ,180
status, inappropriate timing of short- or
mg/dL (10.0 mmol/L), as long as these The sole use of sliding scale insulin is rapid-acting insulin in relation to meals,
targets can be safely achieved. To avoid strongly discouraged in hospitalized reduced infusion rate of intravenous
hypoglycemia, consideration should be patients. A more physiological insulin dextrose, and unexpected interruption
given to reassessing the insulin regimen regimen including basal, prandial, and of enteral feedings or parenteral
if blood glucose levels fall below correctional insulin is recommended. nutrition.
100 mg/dL (5.6 mmol/L). Modifying the The insulin regimen must also
regimen is required when blood glucose incorporate prandial carbohydrate Despite the preventable nature of
values are ,70 mg/dL (3.9 mmol/L), intake (567). For type 1 diabetic many inpatient episodes of
unless the event is easily explained by patients, dosing insulin solely based on hypoglycemia, institutions are more
other factors (such as a missed meal). premeal glucose would likely deliver likely to have nursing protocols for
There is some evidence that systematic suboptimal insulin doses and may hypoglycemia treatment than for its
attention to hyperglycemia in the potentially lead to DKA. It increases prevention. Tracking such episodes
emergency room leads to better both hypoglycemia and hyperglycemia and analyzing their causes are
glycemic control in the hospital for risks and has been shown in a important quality improvement
those subsequently admitted (563). randomized trial to be associated with activities (295).
Patients with a prior history of adverse outcomes in general surgery 4. Diabetes Care Providers in the
successful tight glycemic control in the patients with type 2 diabetes (568). The Hospital
outpatient setting who are clinically reader is referred to publications and Inpatient diabetes management may be
stable may be maintained with a reviews that describe currently effectively championed and/or provided
glucose range below the available insulin preparations and by primary care physicians,
aforementioned cut points. Conversely, protocols and provide guidance in use endocrinologists, intensivists, or
higher glucose ranges may be of insulin therapy in specic clinical hospitalists. Involvement of
acceptable in terminally ill patients or settings including parenteral nutrition appropriately trained specialists or
in patients with severe (569), enteral tube
specialty teams may reduce length of calories to meet metabolic demands, misinterpretation. Most
stay, improve glycemic control, and and create a discharge plan for follow-
improve outcomes (560). Standardized up care (551,573). The ADA does not
orders for scheduled and correction- endorse any single meal plan or
dose insulin should be implemented, specied percentages of
and sole reliance on a sliding scale macronutrients, and the term ADA
regimen strongly discouraged. As diet should no longer be used. Current
hospitals move to comply with nutrition
meaningful use regulations for recommendations advise
electronic health records, as mandated individualization based on treatment
by the Health Information Technology goals, physiological parameters, and
Act, efforts should be made to assure medication use. Consistent
that all components of structured carbohydrate meal plans are preferred
insulin order sets are incorporated into by many hospitals since they facilitate
electronic insulin order sets (570,571). matching the prandial insulin dose to the
A team approach is needed to establish amount of carbohydrate consumed
hospital pathways. To achieve glycemic (574). Because of the complexity of
targets associated with improved nutrition issues in the hospital, a
hospital outcomes, hospitals will need registered dietitian, knowledgeable and
multidisciplinary support to develop skilled in MNT, should serve as an
insulin management protocols that inpatient team member. The dietitian is
effectively and safely enable responsible for integrating information
achievement of glycemic targets (572). about the patients clinical condition,
eating, and lifestyle habits and for
5. Self-Management in the Hospital establishing treatment goals in order to
Diabetes self-management in the determine a realistic plan for nutrition
hospital may be appropriate for therapy (116).
competent youth and adult patients who 7. Bedside Blood Glucose Monitoring
have a stable level of consciousness and Bedside POC blood glucose monitoring
reasonably stable daily insulin is used to guide insulin dosing. In the
requirements, successfully conduct self- patient receiving nutrition, the timing
management of diabetes at home, have of glucose monitoring should match
physical skills needed to successfully carbohydrate exposure. In the patient
self-administer insulin and perform not receiving nutrition, glucose
SMBG, have adequate oral intake, are monitoring is performed every 46 h
procient in carbohydrate counting, use (575,576). More frequent blood glucose
multiple daily insulin injections or testing ranging from every 30 min to
insulin pump therapy, and understand every 2 h is required for patients on
sick-day management. The patient and intravenous insulin infusions.
physician, in consultation with nursing
staff, must agree that patient self- Safety standards should be established
management is appropriate while for blood glucose monitoring
hospitalized. prohibiting sharing of nger-stick
lancing devices, lancets, needles, and
Patients who use CSII pump therapy in meters to reduce the risk of
the outpatient setting can be candidates transmission of blood-borne diseases.
for diabetes self-management in the Shared lancing devices carry essentially
hospital, provided that they have the the same risk as sharing syringes and
mental and physical capacity to do so needles (577).
(560). A hospital policy and procedures
delineating inpatient guidelines for CSII Accuracy of blood glucose
therapy are advisable, and availability measurements using POC meters has
of hospital personnel with expertise in limitations that must be considered.
CSII therapy is essential. It is important Although the FDA allows a 1/2 20%
that nursing personnel document basal error for blood glucose meters,
rates and bolus doses taken on a daily questions about the appropriateness of
basis. these criteria have been raised (388).
Glucose measures differ signicantly
6. MNT in the Hospital between plasma and whole blood,
The goals of MNT are to optimize terms that are often used
glycemic control, provide adequate interchangeably and can lead to
commercially available capillary living or to home, the optimal
blood glucose meters introduce program will need to consider
a correction factor of ;1.12 to the type and severity of
report a plasma- adjusted diabetes, the effects of the
value (578). patients illness on blood
Signicant discrepancies between glucose levels, and the
capillary, venous, and arterial capacities and desires of the
plasma samples have been patient. Smooth transition to
observed in patients with low or outpatient care should be
high hemoglobin concentrations, ensured. The Agency for
hypoperfusion, and the presence Healthcare Research and Quality
of interfering substances
particularly maltose, as contained
in immunoglobulins (579).
Analytical variability has been
described with
several meters (580). Increasingly
newer generation POC blood
glucose meters correct for
variation in
hematocrit and for interfering
substances. Any glucose result that
does not correlate with the
patients status should be
conrmed through
conventional laboratory sampling of
plasma glucose. The FDA has become
increasingly concerned about the use of
POC blood glucose meters in the
hospital and is presently
reviewing matters related to
their use.
8. Discharge Planning and DSME
Transition from the acute care
setting is a high-risk time for all
patients, not
just those with diabetes or new
hyperglycemia. Although
there is an extensive literature
concerning safe
transition within and from the
hospital, little of it is specic to
diabetes (581).
Diabetes discharge planning is not a
separate entity, but is an
important part of an overall
discharge plan. As such,
discharge planning begins at
admission to the hospital and is
updated as projected patient
needs change.
Inpatients may be discharged to
varied settings, including home
(with or without visiting nurse
services), assisted living,
rehabilitation, or skilled nursing
facilities. The latter two sites are
generally staffed by health
professionals, so diabetes
discharge planning will be limited
to communication of medication
and diet orders. For the patient
who is discharged to assisted
S6060 Position Diabetes Care Volume 37, Supplement 1, January 2014
Statement

recommends that, at a minimum, part of discharge planning for DSME should start upon admission or as
discharge plans include the all soon as feasible, especially in those new to
following: patients. insulin therapy or in whom the diabetes
regimen has been substantially altered
c Medication reconciliation: the during the hospitalization.
patients medications must be cross-
checked to ensure that no chronic It is recommended that the following
medications were stopped and to areas of knowledge be reviewed and
ensure the safety of new addressed prior to hospital discharge:
prescriptions.
c Identication of the health care
c Prescriptions for new or changed
provider who will provide diabetes
medication should be lled and
care after discharge
reviewed with the patient and
c Level of understanding related to the
family at or before discharge
diagnosis of diabetes, SMBG, and
c Structured discharge
explanation of home blood glucose goals
communication: Information on
c Denition, recognition, treatment, and
medication changes, pending tests
prevention of hyperglycemia and
and studies, and follow-up needs
hypoglycemia
must be accurately and promptly
c Information on consistent eating
communicated to outpatient
patterns
physicians.
c When and how to take blood
c Discharge summaries should be
glucoselowering medications
transmitted to the primary
including insulin administration (if
physician as soon as possible after
going home on insulin)
discharge.
c Sick-day management
c Appointment keeping behavior is
c Proper use and disposal of needles
enhanced when the inpatient team
and syringes
schedules outpatient medical
follow-up prior to discharge.
It is important that patients be provided
Ideally the inpatient care providers
with appropriate durable medical
or case managers/discharge
equipment, medication, supplies and
planners will schedule follow-up
prescriptions at the time of discharge in
visit(s) with
order to avoid a potentially dangerous
the appropriate professionals,
hiatus in care. These supplies/
including primary care
prescriptions should include the
provider, endocrinologist, and
following:
diabetes educator (582).
c Insulin (vials or pens) if needed
Teaching diabetes self-management to c Syringes or pen needles (if needed)
patients in hospitals is a challenging c Oral medications (if needed)
task. Patients are ill, under increased c Blood glucose meter and strips
stress related to their hospitalization c Lancets and lancing device
and diagnosis, and in an environment c Urine ketone strips (type 1)
not conducive to learning. Ideally, c Glucagon emergency kit (insulin
people with diabetes should be taught treated)
at a time and place conducive to c Medical alert application/charm
learning: as an outpatient in a
recognized program of diabetes More expanded diabetes education can
education. For the hospitalized patient, be arranged in the community. An
diabetes survival skills education is outpatient follow-up visit with the
generally a feasible approach to provide primary care provider, endocrinologist, or
sufcient information and training to diabetes educator within 1 month of
enable safe care at home. Patients discharge is advised for all patients
hospitalized because of a crisis related having hyperglycemia in the hospital.
to diabetes management or poor care at Clear communication with outpatient
home require education to prevent providers either directly or via hospital
subsequent episodes of hospitalization. discharge summaries facilitates safe
Assessing the need for a home health transitions to outpatient care. Providing
referral or referral to an outpatient information regarding the cause or the
diabetes education program should be
care.diabetesjournals.org Position Statement
plan for determining the cause of S6161
hyperglycemia, related complications
and comorbidities, and recommended
treatments can assist outpatient
providers as they assume ongoing care.
B. Diabetes and Employment
Any person with diabetes, whether insulin
treated or noninsulin treated, should be
eligible for any employment for which he or
she is otherwise
qualied. Employment decisions should never
be based on generalizations or stereotypes
regarding the effects of
diabetes. When questions arise about the
medical tness of a person with diabetes for
a particular job, a health care professional
with expertise in treating diabetes should
perform an individualized assessment. See the
ADA position statement on diabetes and
employment (583).

C. Diabetes and Driving


A large percentage of people with
diabetes in the U.S. and elsewhere seek a
license to drive, either for
personal or employment purposes. There
has been considerable debate whether,
and the extent to which, diabetes may be a
relevant factor in determining the driver
ability and eligibility for a license.
People with diabetes are subject to a
great variety of licensing requirements
applied by both state and federal
jurisdictions, which may lead to loss of
employment or signicant restrictions on a
persons license. Presence of a medical
condition that can lead to signicantly
impaired consciousness or cognition may
lead to drivers being
evaluated for tness to drive. For
diabetes, this typically arises when the
person has had a hypoglycemic episode
behind the wheel, even if
this did not lead to a motor vehicle
accident.
Epidemiological and simulator data suggest
that people with insulin-treated diabetes have
a small increase in risk of motor vehicle
accidents, primarily due to hypoglycemia and
decreased awareness of hypoglycemia. This
increase (RR 1.121.19) is much smaller than
the risks associated with teenage male drivers
(RR 42), driving at night (RR 142), driving on
rural roads
compared with urban roads (RR 9.2), individual patient preferences, provision of optimal care of patients
and obstructive sleep apnea (RR 2.4), all prognoses, and comorbidities. B
of which are accepted for unrestricted c A patient-centered communication
licensure. style should be used that
The ADA position statement on diabetes incorporates patient preferences,
and driving (584) recommends against assesses literacy and numeracy,
blanket restrictions based on the and addresses cultural barriers to
diagnosis of diabetes and urges care. B
individual assessment by a health care
professional knowledgeable in diabetes There has been steady improvement in
if restrictions on licensure are being the proportion of diabetic patients
considered. Patients should be achieving recommended levels of A1C,
evaluated for decreased awareness of blood pressure, and LDL cholesterol in
hypoglycemia, hypoglycemia episodes the last 10 years, both in primary care
while driving, or severe hypoglycemia. settings and in endocrinology practices.
Patients with retinopathy or peripheral Mean A1C nationally has declined from
neuropathy require assessment to 7.82% in 19992000 to 7.18% in 2004
determine if those complications based on NHANES data (586). This has
interfere with operation of a motor been accompanied by improvements in
vehicle. Health care professionals lipids and blood pressure control and
should be cognizant of the potential led to substantial reductions in end-
risk of driving with diabetes and stage microvascular complications in
counsel those with diabetes. Nevertheless,
their patients about detecting and between
avoiding hypoglycemia while driving. 33.4 to 48.7% of patients with diabetes
still do not meet targets for glycemic,
D. Diabetes Management in blood pressure, and cholesterol control,
Correctional Institutions and only 14.3% meet targets for the
People with diabetes in correctional combination of all three measures and
facilities should receive care that meets nonsmoking status (317). Evidence also
national standards. Because it is suggests that progress in risk factor
estimated that nearly 80,000 inmates control (particularly tobacco use) may
have diabetes, correctional institutions be slowing (317,587). Certain patient
should have written policies and groups, such as patients with complex
procedures for the management of comorbidities, nancial or other social
diabetes and for training of medical and hardships, and/or limited English
correctional staff in diabetes care prociency, may present particular
practices. See the ADA position
challenges to goal-based care
statement on diabetes management in
(588,589). Persistent variation in quality
correctional institutions (585) for
of diabetes care across providers and
further discussion.
across practice settings even after
adjusting for patient factors indicates
X. STRATEGIES FOR IMPROVING that there remains potential for
DIABETES CARE substantial further improvements in
Recommendations diabetes care.
c Care should be aligned with While numerous interventions to
components of the Chronic Care improve adherence to the
Model (CCM) to ensure productive recommended standards have been
interactions between a prepared implemented, a major barrier to optimal
proactive practice team and an care is a delivery system that too often is
informed activated patient. A fragmented, lacks clinical information
c When feasible, care systems should capabilities, often duplicates services,
support team-based care, community and is poorly designed for the
involvement, patient registries, and coordinated delivery of chronic care.
embedded decision support tools to The CCM has been shown to be an
meet patient needs. B effective framework for improving the
c Treatment decisions should be timely quality of diabetes care (590). The CCM
and based on evidence-based includes six core elements for the
guidelines that are tailored to
with chronic disease: 1) delivery barriers to care (595598);
system design (moving from a integrating evidence-based
reactive to a proactive care guidelines and clinical
delivery system where planned information tools into the
visits are coordinated through a process of care (599601);
team-based approach, 2) self- and
management support, 3) incorporating care
decision support (basing management teams including
care on evidence- based, nurses, pharmacists, and
effective care guidelines), other providers (602604)
4) clinical information systems have each been shown to
(using registries that can optimize provider and team
provide patient- behavior and thereby catalyze
specic and population-based reduction in A1C, blood pressure, and
support to the care team), 5) LDL cholesterol.
community
resources and policies
(identifying or developing
resources to support
healthy lifestyles), and 6) health
systems (to create a quality-oriented
culture). Redenition of the roles
of the clinic staff and promoting
self-
management on the part of the
patient are fundamental to the
successful
implementation of the CCM (591).
Collaborative, multidisciplinary
teams are best suited to provide
such care for people with chronic
conditions such as diabetes and
to facilitate patients
performance of
appropriate self-
management
(222,224,287,592).
NDEP maintains an online resource
(www.betterdiabetescare.nih.g
ov) to help health care
professionals design and
implement more effective
health care delivery systems for
those with
diabetes. Three specic
objectives, with references to
literature that outlines practical
strategies to achieve each, are
outlined below.

Objective 1: Optimize Provider and


Team Behavior
The care team should prioritize
timely and appropriate
intensication of
lifestyle and/or pharmaceutical
therapy of patients who have not
achieved benecial levels of blood
pressure, lipid, or glucose control
(593). Strategies such as explicit
goal setting with patients (594);
identifying and
addressing language,
numeracy, or cultural
Objective 2: Support Patient Behavior incentives to improve diabetes population in 19882006. Diabetes Care
Change care (620). 2010;33:562568
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