F E A T U R E A R T I C L E
Clarifying the Role of Insulin in
Type 2 Diabetes Management
John R. White, Jr., PA-C, PharmD; Stephen N. Davis, MD, FRCP; Ramachandiran Cooppan, MD; Mayer B. Davidson, MD;
Kathryn Mulcahy, RN, MSN, CDE; Gary A. Manko, MD; Donald Nelinson, PhD; and the Diabetes Consortium Medical
D
iabetes is a highly prevalent
chronic disease. The Third
National Health and Nutrition
Examination Survey, conducted between
1988 and 1994, estimated the prevalence
of diagnosed and undiagnosed diabetes
in people aged 20 years and older at
15.6 million.1 Of these people, ~90–95%
have type 2 diabetes, with a higher
prevalence seen among Native
Americans and Americans of African,
Mexican, and Japanese descent.2 The
prevalence of diabetes rose from 4.9%
in 1990 to 6.9% in 1999, primarily
because of an increase in the prevalence
of obesity. It has been postulated that,
with the growing obesity problem, dia-
betes will become an even more perva-
sive threat.3
Type 2 diabetes produces or is a con-
tributor to considerable morbidity in the
form of metabolic complications, vision
disorders, neuropathy, kidney disease,
peripheral vascular disease, ulcerations
and amputations, heart disease, stroke,
digestive diseases, infection, oral com-
plications, and depression. The associat-
ed mortality rate has been estimated at
5.5% annually. Moreover, the disease
reduces life expectancy by 5–10 years.1
Although there is no cure for dia-
betes, two large controlled studies, the
Diabetes Control and Complications Tri-
al (DCCT)4 and the U.K. Prospective
Diabetes Study (UKPDS)5 have pointed
to the importance of intensive blood glu-
cose control in reducing its associated
morbidity. In fact, the UKPDS, the
largest and longest trial ever conducted
in patients with type 2 diabetes, found
that for each 1% reduction in hemoglo-
bin A1c (A1C), there was a 21% decrease
14
Advisory Board
in any endpoint related to diabetes and in
diabetes-related death, a 14% decrease in
all-cause mortality and myocardial
infarction, a 43% decrease in amputation
or death from peripheral vascular dis-
ease, and a 37% decreased risk for
microvascular complications, each of
which was statistically significant.5 The
Japanese Kumamoto study6 also found
that intensive glycemic control reduced
the risk for retinopathy, nephropathy, and
neuropathy in patients with type 2 dia-
betes.
Although sulfonylurea therapy has
been the mainstay of treatment for type 2
diabetes for >40 years, the UKPDS
reported that over a 6-year period, ~53%
of patients who were randomized to
receive treatment with sulfonylureas
needed additional insulin therapy, rein-
forcing the concept that hyperglycemia
in type 2 diabetes is progressive.7 Clini-
cians should consider this when estab-
lishing a therapeutic regimen for patients
with type 2 diabetes.
IN BRIEF
The prevalence of type 2 diabetes has
been increasing rapidly and with it
has been resultant morbidity and mor-
tality. Strict glycemic control reduces
the progression of diabetic microvas-
cular disease; however, most patients
treated with sulfonylureas require
additional insulin therapy. This article
addresses common clinician concerns
about prescribing insulin early in type
2 diabetes. It presents strategies for
incorporating basal insulin therapy
with glargine (Lantus) into a regimen
that promotes compliance.
This article addresses the pathophys-
iology of type 2 diabetes, goals of thera-
py, misconceptions about insulin,
restoration of natural insulin patterns,
and ways to incorporate basal insulin
into a strategy that promotes compliance.
Pathophysiology of Type 2 Diabetes
Type 2 diabetes is characterized by
hyperglycemia caused by defects in
insulin secretion (impaired -cell func-
tion) and insulin action (insulin resist-
ance by the liver and muscle tissue).8–10
These defects occur early in the course
of the disease and are often present
before diagnosis.
In a prospective study11 of Pima Indi-
ans, a group at high risk for developing
diabetes, body composition, insulin
action, insulin secretion, and endogenous
glucose output were measured over sev-
eral years in subjects whose glucose tol-
erance went from normal to impaired to
diabetic. A two-step hyperinsulinemic,
euglycemic glucose clamp test assessed
insulin action. During the transition from
normal to impaired glucose tolerance,
there was a 27% decrease in the acute
insulin secretory response (AIR), the
average incremental plasma insulin con-
centration from the third to the fifth
minute after the glucose bolus. Further-
more, during the transition from
impaired glucose tolerance to diabetes,
there was an additional 57% decrease in
AIR.
Another controlled study in patients
with type 2 diabetes who were either
untreated or attempting to achieve con-
trol using diet or oral hypoglycemic
agents9 found that basal and mean 24-
hour glucose concentrations were signif-
Volume 21, Number 1, 2003 • CLINICAL DIABETES

icantly higher in the diabetic patients,
pointing to potentially impaired insulin
secretion. During the hyperglycemic
clamp portion of this study, patients
secreted ~70% less insulin than control
subjects (Table 1). In nondiabetic indi-
viduals, a biphasic insulin response
begins upon glucose stimulation, starting
with a rapid rise in insulin 1–3 minutes
after the glucose level is raised (first
phase), returning toward baseline 6–10
minutes after glucose stimulation, and
rising gradually once again (second
phase).12 Among patients in this study,
however, the first-phase response after
meals (glycemic load) was either absent
or greatly diminished.9 As a result of
bolus (mealtime) and basal (between-
meal) defects in insulin activity in type 2
diabetes, bolus and basal glucose levels
are increased, producing hyperglycemia.
In the early stages of type 2 diabetes,
blood glucose levels can often be con-
trolled with changes in diet and physical
activity along with sulfonylureas. Unfor-
tunately, the -cell dysfunction that
leads to impaired insulin secretion is
progressive, and eventually patients will
require a treatment strategy that includes
insulin, either alone or with oral agents.7
It should be noted that some patients
who develop diabetes in adulthood have
Table 1. Glucose Concentrations and Insulin Secretion in Control and
Diabetic Subjects Under Three Conditions
Condition Control
Subjects
Fasting
Glucose (mg/dl) 95.2 ± 2.1
Insulin secretion
(nmol/m2/24 hours) 71.7 ± 9.5
24-Hour Study
Glucose (mg/dl) 109.7 ± 1.9
Insulin secretion
(nmol/m2/24 hours) 220.5 ± 30.4
Hyperglycemic Clamp Study
Glucose (mg/dl) 303.6 ± 4.5
Insulin secretion
(nmol/m2/24 hours) 80.6 ± 11.7
Adapted with permission from Ref. 9.
CLINICAL DIABETES • Volume 21, Number 1, 2003
F E A T U R E A R T I C L E
immune-mediated -cell destruction that
is characteristic of type 1 diabetes. This
disease, latent autoimmune diabetes of
adulthood, is often treated in the same
way as type 2 diabetes because it does
not require insulin initially.13
Therapeutic Objective
The American Diabetes Association
(ADA) recommends that patients with
diabetes receive care from a medical
team. Working with patients and their
families, these teams develop self-man-
agement and problem-solving plans that
consider each patient’s cultural, social,
physical, and medical needs. ADA sup-
ports the findings of the DCCT and the
UKPDS for intensive glycemic control;
Table 2 lists its recommendations for
nonpregnant people with diabetes.14
Insulin: Misconceptions and Reality
Contrary to some beliefs, there is no
evidence that doses of insulin used in
clinical practice exacerbate insulin
resistance. It has long been recognized
that the chronic hyperglycemia associ-
ated with type 2 diabetes (glucose toxi-
city) leads to impairment in insulin
secretion and a possible defect in glyco-
gen synthesis.15 In a study of intensive
insulin therapy in patients with type 2
Patients With P almost 3,000 people21 identified high
Diabetes
221.4 ± 19.4 <0.0001
82.7 ± 11.5 NS
282.3 ± 25.6 <0.0001
201.7 ± 19.7 NS
299.8 ± 1.0 NS
24.1 ± 4.1 <0.001
diabetes,16 the use of insulin partially
reversed the postbinding defect in
peripheral insulin action, produced
near-normal basal hepatic glucose out-
put, and enhanced insulin secretion,
thereby maintaining lower glucose val-
ues. In addition, the mean daily insulin
requirement fell by 23% after ~2 weeks
of therapy, leveling off thereafter.
The use of insulin has been associat-
ed with weight gain, which in turn has
been considered a major factor in insulin
resistance. In the UKPDS, patients in
intensive therapy gained more weight
than those in conventional therapy
groups; patients taking insulin gained ~4
kg compared to 2.6 kg for those on
chlorpropamide (Diabinese) and 1.7 kg
for those on glibenclamide (glyburide
[Micronase]).17 Yet patients in the inten-
sive therapy groups also had fewer
microvascular complications, suggesting
that tight glycemic control may be more
important in therapeutic decision-mak-
ing. The use of metformin (Glucophage)
as an adjunct to insulin therapy provides
effective glycemic control without sig-
nificant weight gain.18,19
The incidence of heart disease and
ischemic heart mortality is up to four
times higher in people with diabetes.
Ischemic heart disease, other heart dis-
ease, and cerebrovascular disease
account for 40, 15, and 10% of all deaths
in this population, respectively (Figure
1).20 A population-based survey of
prevalence rates for a constellation of
disorders known as syndrome X, meta-
bolic syndrome, and insulin resistance
syndrome interchangeably—abdominal
obesity, type 2 diabetes, glucose intoler-
ance, hypertension, hypertriglyc-
eridemia, and hypercholesterolemia—
that far exceeded the rates for each
disorder alone or in pairs. For each of
these conditions, fasting and post-glu-
cose hyperinsulinemia was a common
thread that suggested the presence of
insulin resistance. When insulin-resistant
subjects were compared to control sub-
jects, significantly lower HDL choles-
terol levels were also seen.
15
 F E A T U R E A R T I C L E

Table 2. ADA Guidelines for Glycemic Control for Patients With Diabetes betes and several cardiovascular risk fac-
tors, ADA14 recommends the following
Normal Goal Additional action in addition to lifestyle alterations: blood
suggested* pressure measurement at routine medical
Plasma values (mg/dl)† visits; the use of antihypertensive agents
Average preprandial glucose <110 90–130 <90/>150 in patients with hypertension; testing for
Average bedtime glucose <120 110–150 <110/>180 lipid disorders at least annually; lower-
ing LDL and triglycerides; increasing
Whole blood values (mg/dl)‡ HDL and using statins as first-line lipid
Average preprandial glucose <100 80–120 <80/>140 therapy; using fibrates in patients with
Average bedtime glucose <110 100–140 <100/>160 low HDL; and using aspirin therapy to
prevent cardiovascular events.
A1C <6 <7 >8 Clinicians often cite hypoglycemia
The values shown in this table are by necessity generalized to the entire population of individuals as an adverse effect that might preclude
with diabetes. Patients with comorbid diseases, the very young and older adults, and others with the use of insulin. Indeed, in the DCCT
unusual conditions or circumstances may warrant different treatment goals. These values are for non-
pregnant adults. study of type 1 diabetes,4 tighter control
*Values above/below these levels are not “goals” nor are they “acceptable” in most patients. They are produced a risk of severe hypoglycemia
an indication for a significant change in the treatment plan. “Additional action suggested” depends on three times higher than that of conven-
individual patient circumstances. Such actions may include enhanced diabetes self-management edu-
cation, comanagement with a diabetes team, referral to an endocrinologist, change in pharmacologi- tional therapy (Figure 2). This must be
cal therapy, initiation of or increase in self-monitoring of blood glucose, or more frequent contact viewed, however, in the context of sub-
with the patient. A1C is referenced to a nondiabetic range of 4.0–6.0% (mean 5.0%, SD 5%). stantially reduced microvascular and
†Values calibrated to plasma glucose.
‡Measurement of capillary blood glucose. neurological complications. Further-
Reprinted with permission from Ref. 14. more, the rates of severe hypoglycemia
are quite low in type 2 diabetes. In the
Because of the connection among years; the absolute reduction in mortali- Kumamoto study of type 2 diabetes,6
hyperinsulinemia, insulin resistance, and ty was 11%.23 average A1C results were 7.1 and 9.4%
cardiovascular risk factors, the UKPDS17 Other studies24–26 have reported for tight and conventional groups,
compared cardiovascular events among improvement or neutral effects on other respectively. However, only mild hypo-
patients randomized to conventional cardiovascular risk factors—total choles- glycemic reactions occurred and at simi-
lifestyle and dietary management and terol, LDL cholesterol, HDL cholesterol, lar rates in both groups.
those on a tight glycemic control regi- triglycerides, or hypertension—with The UKPDS17 found that the rate of
men with sulfonylureas, metformin (in insulin, even among obese patients. major hypoglycemic episodes (defined
overweight patients), or insulin. No Considering the comorbidity of dia- as an episode in which help from another
adverse effects on cardiovascular out-
comes were seen with any of the treat- 4% 5%
ments, including insulin.
The Diabetes Mellitus Insulin Glu- 13%
cose Infusion in Acute Myocardial 40%
Infarction study22,23 assessed the effect
of acute insulin-glucose infusion fol- 65%
13%
lowed by long-term intensive (multi- 15%
dose) insulin treatment in diabetic
patients who have had an acute 10%
myocardial infarction. Among patients
who had received an acute infusion,
there was a significant decrease in glu- All other
Diabetes
cose. After 1 year, there was a signifi- Malignant neoplasms Ischemic heart disease
cant reduction in mortality in the group Pneumonia/influenza Other heart disease
who received intensive insulin treat-
Cerebrovascular disease
ment, particularly in patients who had a
low cardiovascular risk profile and
were insulin naive.22 These effects per- Figure 1. Cardiovascular and cerebrovascular diseases account for 65% of all
sisted after a mean follow-up of 3.4 deaths in patients with diabetes. Adapted from Ref. 20.

16 Volume 21, Number 1, 2003 • CLINICAL DIABETES

 F E A T U R E A R T I C L E

person or medical intervention was nec-
essary) was higher for patients taking
insulin (2.3%) than for patients undergo-
ing any other intensive therapy or con-
ventional treatment (<1%). The rate of
any hypoglycemic episode (including
episodes that the patient was able to treat
unaided) was 36.5% with insulin treat-
ment, compared to 11, 17.7, and 1.2%
for chlorpropamide, glibenclamide, and
diet, respectively. In a secondary analy-
sis of obese patients on intensive
glycemic control, the rate of major hypo-
glycemic events per year for intensive
insulin treatment was 2.5% versus <1%
for other treatments.
Despite the increased risk of mild
hypoglycemia, aggressive therapy that
combines patient education and self-
management with a form of exogenous
insulin that closely mimics normal
insulin secretion can help to reduce the
morbidity and mortality associated with
type 2 diabetes.
Restoring Natural Insulin Patterns
Nondiabetic pancreases self-regulate the
amount of insulin secreted, acting in
response to changes in blood glucose
120
100
Rate of Severe Hypoglycemia
concentration that result from the inges-
tion of food. In people with diabetes,
however, bolus and basal glucose levels
are increased; thus, strategies for insulin
replacement must focus on mimicking
the phases of insulin secretion. Figure 3
shows available insulins by onset, peak,
and usual effective duration.27
Prandial (Bolus) Insulin
Prandial forms of insulin mimic the nor-
mal first-phase response. These regular
insulin or rapid-acting insulin analogs
are administered 30–60 minutes (regu-
lar) or 10–15 minutes (lispro [Humalog]
or aspart [Novolog]) before food con-
sumption. They must also mimic the
second-phase response, requiring a more
prolonged duration of action to control
prolonged glucose elevation after the
meal.28 Although prandial forms offer
flexibility in that they can be injected
just before a meal, most patients also
require daily basal insulin injections.29
Basal Insulin
Both intermediate (NPH and lente) and
long-acting (ultralente and glargine
[Lantus]) insulins have been used to
mimic physiological basal insulin secre-
tion, with varying results. An insulin that
mimics basal secretion should be slowly
and evenly absorbed with no peak, have
consistent bioavailability, and have a
long half-life that permits once-daily
administration.30,31 This has not been the
case with most basal insulin products.
NPH and lente have early peaks with
rapid waning of action; this may con-
tribute to both nighttime hypoglycemia
and the “dawn phenomenon,” a pre-
breakfast rise in plasma glucose. There
is also variability in the absorption of
NPH and lente.29,32 Data on ultralente
vary; in one study of type 1 diabetes,30
the onset of action of human ultralente
was 2–4 hours, and there was a broad,
variable peak 6–12 hours after injection.
The authors concluded that this product
did not provide a constant basal insulin
concentration.
Basal insulin in type 1 diabetes. The
pharmacokinetics and pharmacodynam-
ics of the insulin analog glargine were
compared to those of NPH, ultralente,
and continuous subcutaneous insulin
infusion (CSII) of lispro in 20 type 1 dia-
betic patients using an isoglycemic 24-
hour clamp.33 Glargine was absorbed
slowly and produced no pronounced
peaks over a 24-hour period. Its onset of
action was ~1.5 hours, compared with

0.8 hours for NPH, 1 hour for ultralente,

(per 100 patient-years)

and 0.5 hours for CSII. Its concentra-

80
tion/action profile was similar to CSII,
with lower intersubject variability than
60 with NPH and ultralente. These factors
make glargine an excellent choice for
40 basal insulin replacement.
In another study of type 1 diabetes,34
256 patients were randomized to receive
20
NPH (once daily at bedtime or twice dai-
ly before breakfast and at bedtime) or
0 glargine once daily at bedtime. After 1
5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 week and sustained throughout the 4-
Glycosylated Hemoglobin (%) week study, fasting plasma glucose was
Figure 2. Rate of severe hypoglycemia in patients receiving intensive therapy. As significantly lower in the pooled glargine
tighter glycemic control is attained, the risk of severe hypoglycemia increases. groups than in the NPH group (165.6 vs.
Points, which correspond to more than 400 patient-years, indicate crude rates 203.4 mg/dl, respectively; P = 0.0001).
within deciles of the mean glycosylated hemoglobin (A1C) values during the Patients who had been taking NPH twice
trial. ©Copyright 1988 Massachusetts Medical Society. All rights reserved. daily before the study were more likely
Adapted with permission, 2002. to demonstrate greater improvement if

CLINICAL DIABETES • Volume 21, Number 1, 2003 17


Glargine
Ultralente
Lente
NPH
Regular
Lispro
Aspart
0 2 4 6 8 10
Hours
Figure 3. The action of human insulins. Onset, peak, and usual effective dura-
tions vary among available insulins. In some reports, ultralente has demonstrat-
ed a peak concentration after several hours, followed by waning. Values shown
are the mean in each range. Adapted with permission from Ref. 27.
randomized to a glargine group than
were patients previously on once-daily
NPH. The longer duration of glargine
also provided a statistically significant
advantage in reducing the likelihood of
the dawn phenomenon.
Basal insulin in type 2 diabetes. The
management of type 2 diabetes has tradi-
tionally followed a stepped approach of
lifestyle changes, to oral agents, to com-
binations of oral agents, to insulin.
Along the way, however, complications
resulting from poor glycemic control
may occur, some of which might have
been reduced or possibly avoided with
the early introduction of insulin.35
Many studies have evaluated how to
use insulin effectively for the treatment
of type 2 diabetes. Two- and four-dose
regimens of NPH improved glycemic
control but caused basal hyperinsuline-
mia.36 The addition of 70/30 insulin (a
premixed formulation with 30% fast-
acting insulin and 70% intermediate-
acting insulin) before supper to
glimepiride (Amaryl) restored glycemic
control more quickly than did 70/30
insulin alone, without producing severe
hypoglycemia.25 The addition of NPH
to glipizide (Glucotrol) was superior to
18
F E A T U R E A R T I C L E
Onset
Peak
Duration
12 14 16 18 20 22 24
high- and low-dose NPH alone in
restoring glycemic control.37 Combina-
tion therapy with an intermediate-acting
insulin at bedtime plus metformin was
superior to bedtime insulin plus gly-
buride and metformin, bedtime insulin
plus glyburide, and insulin twice daily
and produced no weight gain.18 The
addition of evening NPH to existing
oral agents was similar in efficacy to
morning NPH plus an existing antidia-
betic agent, a two-injection regimen of
70/30 insulin, multiple injections, and
oral hypoglycemic agents alone; howev-
er, this regimen did not induce as much
weight gain and hyperinsulinemia.38
Recent clinical trials suggest that
glargine provides basal insulin glycemic
control equal to that of NPH with less
risk of hypoglycemia. Glargine has been
evaluated in patients with type 2 diabetes
in a trial comprising 518 patients who
had been receiving NPH with or without
regular insulin for postprandial control.39
This 28-week, multicenter, open-label
comparison of NPH once or twice daily
and glargine once daily at bedtime
reported similar decreases in A1C but a
lower risk of nocturnal hypoglycemia
with glargine compared with NPH (26.5
vs. 35.5%; P = 0.016). There was signifi-
cantly less weight gain with glargine
than with NPH (0.4 vs. 1.4 kg; P =
0.0007).
A 6-month, multicenter, random-
ized, open-label trial40 compared the
addition of glargine or NPH to an oral
therapy regimen to restore glycemic
control to a target A1C ≤7% in 756
insulin-naïve patients with type 2 dia-
betes. A1C results were lower in both
treatment groups and ≤7% in 58% of
patients. At the end of the study, the
mean glargine dose was higher than that
of NPH; however, symptomatic hypo-
glycemia rates, particularly nocturnal
hypoglycemia, were significantly lower
in the glargine group. Risk was reduced
by 21% for any incidence of hypo-
glycemia and by 42% for nocturnal
hypoglycemia (Table 3).
Other studies comparing glargine to
NPH at bedtime reported that similar
control was achieved with each agent;
however, there were significantly less
hypoglycemia41 and significantly lower
postdinner glucose concentrations42 with
glargine than with NPH. Among insulin-
naive patients and overweight patients
who had been taking oral agents with or
without insulin, significantly fewer
receiving glargine experienced nocturnal
hypoglycemia.43
An Algorithm for Using Insulin
There is no single best way to initiate
insulin therapy in patients with type 2
diabetes in whom oral treatments no
longer maintain adequate control.
Clinicians should consider 10 units of
basal insulin at bedtime, supper, or in
the morning a safe, effective recommen-
dation for beginning insulin therapy.
This dose can then be titrated based on
how well a patient has met individual
glycemic goals as measured by fasting
blood glucose, postmeal glucose levels,
and self-monitoring of blood glucose. In
obese, insulin-resistant patients, a higher
starting dose may be safely used.
Figure 444 provides an algorithm that
includes recommendations for the use of
insulin therapy in type 2 diabetes.
Volume 21, Number 1, 2003 • CLINICAL DIABETES
 F E A T U R E A R T I C L E

Table 3. Relative Risk of Hypoglycemic Episodes per Patient-Year
Hypoglycemia Glargine
(%)
All confirmed 13.9
Nocturnal confirmed 4.0
Adapted with permission from Ref. 40.
Compliance
Patients with diabetes play an integral
role in any treatment strategy. Lifestyle
modification; goal setting; self moni-
toring; preventing, detecting, and treat-
ing acute complications; and using
medications correctly are all important
components in achieving glycemic
control.45 This makes patient education
crucial, particularly when it comes to
dispelling myths about insulin therapy.
The content areas that must be clearly
established for patients are listed in
Table 4.
The relationship between health care
provider and patient is crucial to compli-
NPH (%) P Relative Risk With
Glargine (%)
17.7 <0.02 21
6.9 <0.001 42
ance. In the management of diabetes,
this is more than a relationship between
the patient and a single provider—it
includes an entire health care team.
Other factors also influence compli-
ance. On the patient’s side, the belief that
the benefits of therapy are worth the con-
sequences, a readiness to change, memo-
ry, communication skills, literacy level,
knowledge, competence, confidence,
skills, and a good support system work
together to influence the patient’s accept-
ance of therapy. On the team’s side,
communication skills, the quality of
information and instructions, and a will-
ingness to identify and address barriers
affect compliance. The regimen itself is
also a factor; if it is difficult, costly, or
has many side effects, compliance may
diminish.46–49
In the treatment of type 2 diabetes
with insulin, reluctance to inject oneself
and fear of weight gain or hypoglycemia
may hinder compliance.35 Clinicians
need to explain to their patients that type
2 diabetes is progressive and that insulin
will probably have to be used at some
point; therefore, clinicians may need to
dispel myths associated with insulin use,
allay patient fears, and assure patients
that insulin will likely improve symp-
toms, enhance quality of life, and pro-
vide a sense of well-being.
“Resistance to insulin” on the part of
clinicians may also be a significant
provider-driven factor in compliance.50
Concerns regarding hypoglycemia,
patients’ fear of needles, cultural health
beliefs, and the time necessary to teach
self-injection can all emerge as barriers
to insulin use.

Test for diabetes

No
MNT, physical activity, Yes
risk factor reduction Assess for severe symptoms
(polydypsia, polyuria, weight loss)
No Yes

Retest for diabetes MNT, physical activity, DSME, Insulin therapy, MNT, physical
in 1 year risk factor reduction, SMBG activity, DSME, risk reduction
No more than 12 weeks

Reassess for type 2 diabetes

FPG 126–140 mg/dl FPG 140–160 mg/dl FPG >160 mg/dl
Or A1C <6.5% Asymptomatic
or A1C 6.5%–8.0% or A1C >8.0% type 2 Diabetes Type 1 diabetes
or type 2 with
Adjust management to achieve a perisistent severe
target FPG level of 70 to 110 mg/dl; Combination therapy: symptoms
Reassess every 3 months Dose titration period 3–12
weeks
Continue insulin
Monotherapy Suggested combinations: therapy
Dose titration period: 3–12 weeks Secretagogues + meformin or
TZD or AGI
Key to Abbreviations: Metformin + TZD
FPG: Fasting Plasma Glucose A1C ≤6.5% A1C >6.5%
TZD: Thiazolidinedione
AGI: Alpha-Glucosidase Inhibitor
A1C ≤6.5% A1C >6.5%
DSME: Diabetes Self-
Management Education
MNT: Medical Nutrition Therapy Continue therapy: Add insulin;
SMBG: Self-Monitoring of Blood
Reassess every 3 months Dose titration period 3–12 weeks
Glucose

Figure 4. An algorithm of treatment for patients with type 2 diabetes. Reprinted with permission from Ref. 44.

CLINICAL DIABETES • Volume 21, Number 1, 2003 19


Table 4. Content Areas for Diabetes Self-Management Education
• The disease process and its treatment
• Nutrition and exercise goals
• Appropriate use of medications
• Monitoring of blood glucose and urine and blood ketones to improve control
• Prevention, recognition, and treatment of acute and chronic complications
• Goal-setting and problem-solving
• Psychosocial adjustment
• Counseling about pregnancy and diabetes, if appropriate
Adapted with permission from Ref. 45.
Conclusions
With the prevalence of type 2 diabetes
on the rise and with the recognized need
for strict glycemic control in the preven-
tion of complications, strategies for
aggressive treatment must be put into
effect. Such strategies might include the
early use of insulin, alone or in combi-
nation with other antidiabetic agents.
Clinicians must weigh the risks associat-
ed with the use of insulin against the
benefits. Several studies have clearly
shown that basal insulin therapy, partic-
ularly using the insulin analog glargine,
closely mimics the body’s physiological
secretion of basal insulin and may be
added to an existing oral regimen, used
alone, or used with preprandial insulin.
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1
Harris MI, Flegal KM, Cowie CC, Eberhardt
MS, Goldstein DE, Little RR, Wiedmeyer H-M,
Byrd-Holt DD: Prevalence of diabetes, impaired
fasting glucose, and impaired glucose tolerance
in U.S. adults: the Third National Health and
Nutrition Examination Survey, 1988–1994. Dia-
betes Care 21:518–524, 1998
2
Harris MI: Summary. In Diabetes in Ameri-
ca. 2nd ed. National Diabetes Data Group,
National Institutes of Health, National Institute of
Diabetes and Digestive and Kidney Diseases,
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CLINICAL DIABETES • Volume 21, Number 1, 2003
F E A T U R E A R T I C L E
42
Yki-Järvinen H, Dressler A, Ziemen M, Stephen N. Davis, MD, FRCP, is chief
HOE 901/3002 Study Group: Less nocturnal
hypoglycemia and better post-dinner glucose of the Division of Diabetes, Endocrinol-
control with bedtime insulin glargine compared ogy, and Metabolism at Vanderbilt Uni-
with bedtime NPH insulin during insulin combi-
nation therapy in type 2 diabetes. Diabetes Care versity Medical School in Nashville,
23:1130–1136, 2000 Tenn. Ramachandiran Cooppan, MD, is
43
Benedetti MM, Hamburg E, Dressler A, Zie- an assistant clinical professor at Har-
man M, for the 3002 Study Group: Lower inci-
dence of nocturnal hypoglycaemia in patients
vard Medical School in Boston, Mass.
with type 2 diabetes treated with insulin glargine Mayer B. Davidson, MD, is director of
compared with NPH insulin, given as a combina-
tion regimen with oral agents (Poster). Presented
the Clinical Trials Unit at Charles R.
at the 38th annual meeting of the European Asso- Drew University in Los Angeles, Calif.
ciation for the Study of Diabetes. Budapest, Hun-
gary, September 1–5, 2002
Kathryn Mulcahy, RN, MSN, CDE, is
44
program director of the INOVA Dia-
IAFP Family Practice Education Network:
Type 2 diabetes: diagnosis and management betes Center in Fairfax, Va. Gary A.
strategies for primary care clinicians: consensus Manko, MD, is president of Clinical
recommendations from an expert panel. Ill Acad
Fam Phys 1–12, 2002 Associates, PA, in Reisterstown, Md.
Donald Nelinson, PhD, is executive
45
Mensing C, Boucher J, Cypress M, Weinger
K, Mulcahy K, Barta P, Hosey G, Kopher W, director of the Diabetes Consortium.
Lasichak A, Lamb B, Mangan M, Norman J, Tan-
ja J, Yauk L, Wisdom K, Adams C: National
The Diabetes Consortium, Inc., is a
standards for diabetes self-management educa- nonprofit, multidisciplinary collabora-
tion. Diabetes Care 25 (Suppl. 1):S140–S147, tion dedicated to the development and
2002
46
dissemination of professional and
Meichenbaum D, Turk DC: Facilitating
Treatment Adherence. New York, Plenum Press, patient initiatives implementing optimal
1987 diabetes care. For more information,
47
Ewart CK: Social action theory for a public write to: P.O. Box 8262, Parsippany,
health psychology. Am Psychol 46:931–946, 1991
NJ, 07054-8262, or call 877-462-4356.
48
Williams GC, Quill TE, Deci EL, Ryan RM:
“The facts concerning the recent carnival of
smoking in Connecticut” and elsewhere. Ann Note of disclosure: Dr. White has served
Intern Med 115:59–63, 1991 on an advisory board for Aventis; has
49
Williams MV, Parker RM, Baker DW, received honoraria for speaking engage-
Parikh NS, Pitkin K, Coates WC, Nurss JR: Inad- ments from Aventis, Takeda, Omron,
equate functional health literacy among patients
at two public health hospitals. JAMA Pfizer, and TheraSense; and has received
274:1677–1682, 1995
research support from Aventis. Dr. Coop-
50
Guise BJ, Nelinson DS, Beyond the Pre- pan has received honoraria from Bristol-
scription: Promoting Patient Compliance, CME
Monograph–Center for Health Education. Octo- Myers Squibb, Pfizer, Aventis, Novartis,
ber 30, 1999, p.2–3 Takeda, Eli Lilly, GlaxoSmithKline, and
Wyeth-Ayerst. Ms. Mulcahy has served
ACKNOWLEDGMENT on advisory boards and received hono-
raria from Aventis and Novo Nordisk. Dr.
The research for this article was sup- Manko has received honoraria from
ported by an unrestricted grant from Pharmacia, Wyeth-Ayerst, and Bristol-
Aventis. Myers Squibb. All of these companies
manufacture or market insulin or other
John R. White, Jr., PA-C, PharmD, is a pharmaceutical products for the treat-
professor at Washington State Universi- ment of type 2 diabetes or its complica-
ty College of Pharmacy in Spokane. tions.
21