Clinical Therapeutics/Volume 35, Number 5, 2013
Inpatient Management of Diabetes and Hyperglycemia
Magdalena Bogun, MD; and Silvio E. Inzucchi, MD
Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut
ABSTRACT
Illness, particularly when severe, leads to increased
concentrations of counter-regulatory factors which in-
duce insulin resistance and predispose patients to stress
hyperglycemia. Elevated glucose concentrations are
common in hospitalized patients, both those with as
well as without recognized diabetes. Substantial data
has emerged over the past decade that quality glucose
management in these individuals actually improves
clinical outcomes. Controlling glucose in this setting is
challenging, given the phenotypic variability amongst
patients, with fluctuating courses of acute illnesses and
unpredictable nutritional schedules. We review the ev-
idence basis that has informed national standards and
glucose targets in both critically and non-critically ill
patients. In the intensive care setting, insulin infusions
are now widely endorsed to quickly achieve and main-
tain glucose control. On the hospital wards, physiolog-
ical subcutaneous insulin therapy, incorporating both
basal and nutritional components, is emerging as the
optimal treatment strategy. The transition to outpa-
tient care is another important aspect of any hospital
glycemic management program. (Clin Ther. 2013;35:
724733) 2013 Published by Elsevier HS Journals,
Inc.
Key words: diabetes, hyperglycemia, hospital, inpa-
tient, critical care, insulin infusion
INTRODUCTION
Hyperglycemia in hospitalized patients with or with-
out overt diabetes presents complex management is-
sues. Questions arise about the degree of intensity to
which glucose levels should be maintained in the criti-
cal care setting, step-down units, and general medical-
surgical wards, as well as the optimal strategies for
subsequent transitions to outpatient care.
Glucose Control During Critical Care
There is a well-recognized relationship between glu-
cose levels and adverse clinical outcomes in the criti-
cally ill. In 2003, Krinsley et al1 reported that in a
mixed medical-surgical intensive care unit (ICU), mor-
724
tality increased progressively as mean blood glucose
concentrations increased. For example, mortality was
9.6% in patients whose mean ICU glucose concentra-
tion fell between 80 and 99 mg/dL but was 4-fold
higher (42.5%) in those whose mean glucose exceeded
300 mg/dL. Similarly, Kosiborod et al2 in 2008 re-
ported that in patients hospitalized for acute myocar-
dial infarction (AMI), mortality increased progres-
sively with every 10-mg/dL glucose increase above 120
mg/dL, after controlling for a variety of important clin-
ical variables (Slide 1). This relationship was particu-
larly striking in those without an antecedent history of
diabetes. These data were consistent with those from
an early observational study from Umpierrez et al3 in-
volving 2030 ICU patients, which concluded that those
with newly identified hyperglycemia had significantly
higher mortality (31%) than did patients with known
diabetes (11%). Notably, in the Kosiborod analysis,4
an increase in mortality was also seen when mean
blood glucose fell below 70 mg/dL.
These studies raise the possibility that controlling
blood glucose in the setting of critical illness may im-
prove clinical outcomes but also that overly intensive
approaches might be counterproductive. Yet observa-
tional data alone can be misleading and are influenced
by confounding factors that are either not easily as-
sessed or not initially considered to be relevant by the
investigators. So, it remained unknown as to whether
hyperglycemia merely serves as a marker of poor clin-
ical outcomes or represents a true mediator of these
adverse events. It is well-recognized that illness by it-
self, particularly when severe, leads to stress hyper-
glycemia through the activation of counter-regula-
tory hormones, primarily cortisol and epinephrine,
which increase endogenous glucose production and de-
crease glucose uptake into peripheral tissues, while
also elevating circulating levels of free fatty acids
Accepted for publication April 19, 2013.
http://dx.doi.org/10.1016/j.clinthera.2013.04.008
0149-2918/$ - see front matter
2013 Published by Elsevier HS Journals, Inc.
Volume 35 Number 5
 M. Bogun and S.E. Inzucchi

Mean Glucose & In-Hospital Mortality in Patients with AMI

20
No Diabetes

All Patients

Diabetes
15
Odds Ratio

10
N = 16,871

1
0
t 70
90 to 0
10 to 90
11 to < 00
12 to 10
13 to 20
14 to 30
15 to 40
16 to 50
17 to 60
18 to < 70
19 to 80
20 to 90
21 to 00
22 to 10
23 to < 20
24 to 30
25 to < 40
26 to 50
27 to 60
28 to 70
29 to < 80
to 0

3 0
00
80 o <8

0 29

0
70 <

<
0 <1
0 1
0 <1
0 <1
0 <1
0 <1
0 <1
0 <1
0 1
0 <1
0 <2
0 <2
0 <2
0 2
0 <2
0 2
0 <2
0 <2
0 <2

<3
Mean BG (mg/dL)

(Reference: Mean BG 100110 mg/dl)

(Referance: Mean BG 100-110 mg/dl)

Slide 1. Relationship between mean glucose levels and mortality during hospitalization for nearly 17,000 acute
myocardial infarction patients. Hyperglycemia is associated with more adverse outcomes, especially in non-
diabetic individuals. Reprinted with permission from Kosiborod M et al. Circulation 2008;117:1018 1027.2

through the stimulation of lipolysis (Slide 2). Conversely,
increased glucose and fatty acids may secondarily exac-
erbate illness through altered tissue metabolism, oxida-
tive stress, hypercoagulability, and suppressed immunity
and wound healing.
The first study to explore the notion of controlling
glucose in the ICU to improve patient outcomes was
conducted by cardiothoracic surgeons, led by Fu-
nary.5 In this nonrandomized trial, patients under-
going cardiac surgery were placed on an insulin-in-
fusion regimen for 3 days postoperatively, targeting
a glucose level of 151 to 200 mg/dL. Their outcomes
were compared to those from a historical control
group who were mainly managed conventionally with
subcutaneous regular human insulin (every 4 hours on a
sliding scale with a target of 200 mg/dL). Deep sternal
wound infections occurred in 0.8% of the study group
and in 2.0% of the controls (relative risk [RR] reduc-
tion, 66%; P 0.01). Impressively, the annual rates of
deep sternal wound infections in diabetic patients at the
end of the study had reached the rates similar to those in
nondiabetic individuals. The nonrandomized nature of
this study, however, limited the conclusiveness of its
findings.
The DIGAMI (Diabetes Insulin-Glucose Infusion in
Acute Myocardial Infarction) study6 examined the
short- and long-term effects of intensive insulin treat-
ment in patients with diabetes during and soon after
AMI. A total of 360 patients were randomly assigned
within 24 hours of admission to receive an intravenous
infusion of insulin (and glucose) for 48 hours, with a
target blood glucose level of 126 to 196 mg/dL, fol-
lowed by multidose subcutaneous insulin injections for
3 months. A total of 314 patients in the control group
received conventional diabetes care. An 11% absolute
and a 28% relative mortality risk reduction was dem-

May 2013 725

 Clinical Therapeutics
Illness leads to stress hyperglycemia
Illness
Stress hormones Glucose Hemodynamic insult
cortisol, epinephrine Production Electrolyte losses
Oxidative stress
+ Myocardial injury
Glucose FFAs Hypercoagulability
Fatty Acids Altered immunity
Wound healing
Inflammation
Endothelial function
Glucose Uptake
Lipolysis
FFAs
Stress hyperglycemia may also exacerbate illness.
Slide 2. Schematic overview of the relationship be-
tween stress hyperglycemia and illness.
Through counter-regulatory hormones, ill-
ness promotes increased circulating glucose
and free fatty acid concentrations. These, in
turn, theoretically, could exacerbate illness
through the intermediary effects listed.
onstrated after 5 years in the intensive insulin therapy
group, with a predetermined low-risk subgroup (based
on severity of AMI presentation and no history of in-
sulin use) showing even greater effects (15% and 51%,
respectively). Most of the benefit was apparent in the
first month of treatment, suggesting some influence
from the immediate infusion of insulin. The survival
curves tended to separate further over time, implying
an ongoing benefit from intensive treatment. The in-
vestigators concluded that intensive insulin therapy
might be an appropriate treatment for diabetic patients
at the time of acute cardiovascular events. However,
subsequent studies (HI-5 [Hyperglycemia: Intensive
Insulin Infusion in Infarction],7 DIGAMI-2 [diabe-
tes mellitus and acute myocardial infarction],8 and
CREATE-ECLA [Clinical Trial of Metabolic Modula-
tion in Acute Myocardial Infarction Treatment Evalu-
ation]9) did not replicate these findings, although these
latter investigations were marred by methodologic
flaws and/or low patient recruitment.
A prospective, randomized, controlled study from
Leuven, Belgium, involved 1548 patients who received
standard or intensive antihyperglycemic treatment after
admission to a surgical ICU with a preponderance of car-
diac surgery patients.10 In the intensive-treatment group,
the blood glucose levels were maintained in a strict eugly-
726
cemic range (80 110 mg/dL) by intravenous insulin infu-
sion. The conventional-treatment group were targeted
between 180 and 200 mg/dL, with IV insulin being ad-
ministered only if glucose exceeded 215 mg/dL; other-
wise, intermittent subcutaneous injections of regular hu-
man insulin were used. At the conclusion of the trial,
those in the intensive-treatment group had significantly
fewer deaths in the ICU compared with the conventional-
treatment group (63/783 vs 35/765; P 0.04), a RR
reduction of 42% (P 0.04). Intensive glycemic manage-
ment was also associated with a 34% reduction in total
in-hospital mortality (55/764 vs 85/783; P 0.01) in
total in-hospital patients (Slide 3). This widely publicized
study has been credited with leading to a major change in
practice in ICUs across the United States, with many in-
stitutions implementing similar intensive glucose-man-
agement protocols. Notably, however, in a follow-up
study11 from this group involving their medical ICU, no
mortality benefit could be demonstrated with intensive
insulin therapy, although in a predetermined group of
patients with longer ICU stays (5 days), mortality was
reduced from 26.3% to 16.8% (P 0.01).
Subsequent to the Leuven investigations, several other
studies published from a variety of critical care settings
could not confirm the initial encouraging findings.12,13
The largest of these, NICE-SUGAR (Normoglycaemia in
Intensive Care Evaluation and Survival Using Glucose
Algorithm Regulation),12 suggested that intensive glu-
cose control with intravenous insulin (target, 81108 mg/
dL) might increase mortality compared with maintaining
glycemia in the more moderate range of 140 to 180
mg/dL through conventional methods (Slide 4). The rea-
son for the higher mortality in the active-treatment group
in NICE-SUGAR has never been fully elucidated. One
theory relates to the much higher rate of severely high
glucose levels (40 mg/dL) in the intensive-treatment
group (6.8% vs 0.5%), although a cause-and-effect rela-
tionship could not be confirmed. It should be noted, how-
ever, that a larger number of patients assigned to inten-
sive treatment withdrew early from the study and did not
receive insulin infusion. Because a per-protocol (or com-
pleters) analysis of the data has never been published, it
remains unclear as to whether those who received inten-
sive insulin therapy experienced greater mortality.
Griesdale et al13 have since published a meta-anal-
ysis including 26 randomized control trials that as-
sessed the effects of intensive glucose management, in-
volving a total of 13,567 critically ill patients. Here,
the RR (95% CI) for death with more intensive insu-
Volume 35 Number 5
 M. Bogun and S.E. Inzucchi

Intensive Insulin Therapy in the Surgical ICU: The Leuven Study

A 100 B 100

96 96
Intensive treatment

In-Hospital Survival (%)

Intensive treatment
Survival in ICU (%)

92 92
Conventional treatment

88 88 Conventional treatment

MORTALITY 42% MORTALITY 34%

84 84
P < 0.04 P < 0.01

80 80
0 0
0 20 40 60 80 100 120 140 160 0 50 100 150 200 250
Days After Admission Days After Admission

Slide 3. KaplanMeier survival curves from the Leuven SICU study. More intensive glucose control with IV insulin resulted in
lower ICU and in-hospital mortality among the 1548 patients studied. From N Engl J Med, van den Berghe G,
Wouters P, Weekers R, et al, Intensive insulin therapy in critically ill patients, 3459, 13591367. Copyright 2001
Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.10

NICE-SUGAR Trial: Outcomes

180 1.0

160
Conventional 0.9
Probability of Survival

140
BG, mg/dL

0.8 Conventional
120 Intensive
108 Intensive
0.7
100

P = 0.03
80 0.6
0 0
Base- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 0 10 20 30 40 50 60 70 80 90
line Days After Randomization Days After Randomization

3054 received IIT goal: 81108 mg/dL 90-day mortality: IIT: 829 patients (27.5%), CIT: 751
(time weighted BG = 118 mg/dL) (24.9%)

3050 received CIT goal: <180 mg/dL Absolute mortality difference: 2.6%
(time-weighted BG = 145 mg/dL) (95% CI, 0.44.8)
Odds ratio for death with IIT:
1.14 (95% CI, 1.021.28; P = 0.02)

Slide 4. Glycemic control and KaplanMeier survival curve from the NICE-SUGAR study. Despite lower glucose
levels in the intensive group, mortality was increased. The explanation for this finding has remained
elusive. From N Engl J Med, Finfer S, Chittock DR, Su SY, et al, for the NICE-SUGAR Study Investigators,
Intensive versus conventional glucose control in critically ill patients, 3603, 12831297. Copyright
2009 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.12

May 2013 727

 Clinical Therapeutics

New AACE-ADA Consensus

Statement on Inpatient Glycemic Control

ICU Setting NonICU Setting

Insulin infusion preferred
Starting threshold not higher than
180 mg/dl
Maintain BG 140180 mg/dl
(greater benefit likely at lower end of
this range)
Lower targets (not evidence-based)
may be appropriate in selected
patients if already being successfully
achieved
<110 NOT recommended
(not safe)
Most patients:
pre-meal BG <140 mg/dL
random BG <180 mg/dL
More stringent targets may be
appropriate in stable patients
Less stringent targets may be
appropriate in patients with severe
comorbidities
Scheduled SQ insulin with basal-
nutritional-correction preferred; avoid
prolonged therapy RISS alone

AACE, American Association of Clinical Endocrinologists; ADA, American Diabetes Association;

SQ, subcutaneous; RISS, regular insulin sliding scale.

Slide 5. Major recommendations from the AACE-ADA Consensus Statement on inpatient glycemic control.
Moghissi ES, Korytkowski MT, Di-Nardo M, et al. American Association of Clinical Endocrinologists and
American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;
32:1119 1131.15 and Moghissi ES, Korytkowski MT, Di-Nardo M, et al. American Association of
Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glyce-
mic control. Endocr Pract. 2009;15:353369.26

lin therapy was statistically indistinguishable com-
pared to that with conventional approaches (0.93
[0.831.04]). The RR, however, varied according to
the type of unit, with intensive insulin showing appar-
ent benefit in the surgical ICU setting (0.63 [0.44
0.91]) but not in mixed ICUs (0.99 [0.871.12]) or
medical ICUs (1.00 [0.78 1.28]). Fourteen of those
trials reported hypoglycemia, and not surprisingly the
RR for severe hypoglycemia in the intensive insulin
therapy group was 6.0 (4.5 8.0). Although earlier tri-
als have linked hypoglycemia to increased mortality,
its cause-and-effect relationship is not clear. Kosiborod
et al14 reported that hypoglycemia is more likely to be a
predictor of the severity of illness than a direct cause of
mortality. In his study involving hyperglycemic patients
during AMI, hypoglycemia was associated with higher
mortality only in those patients not treated with insulin
(odds ratio [OR] 2.32 [95% CI, 1.31 4.12]). Those
who developed hypoglycemia and were being treated
with insulin had mortality similar to those who experi-
enced no hypoglycemia (OR 0.92 [0.58 1.45]).
These often-conflicting sets of data led the American
Association of Clinical Endocrinology (AACE) and the
American Diabetes Association (ADA) to develop con-
sensus recommendations concerning the management
of hyperglycemia in the hospital15 (Slide 5). According
to this AACE-ADA statement, which was more mod-
erate in tone than were prior guidelines, intensive glu-
cose control with insulin infusion should be under-
taken in those ICU patients (regardless of prior
diabetes history) with blood glucose 180 mg/dL, and
maintained between 140 and 180 mg/dL, with greater
benefit believed to be likely at the lower end of this
range. The consensus panel went on to note that some-
what lower targets (110 140 mg/dL) might be appro-
priate in select patients but that blood glucose targets
110 mg/dL could no longer recommended.
Insulin Infusions
A successful intravenous insulin protocol consis-
tently reaches and maintains blood glucose success-
fully within a specified target range while minimizing
hypoglycemia (and providing specific directions for the
treatment of hypoglycemia if it does occur). The pro-
tocol should have a clear, nurse-driven algorithm for
making temporary corrective changes in the insulin rate
as a patients glucose levels and degree of insulin sensitiv-
ity change. The most successful protocols incorporate not

728 Volume 35 Number 5

 M. Bogun and S.E. Inzucchi

Yale Adult ICU Insulin Infusion Protocol (IIP)

Slide 6. The Yale Insulin Infusion Protocol. Reprinted with permission from Shetty S, Inzucchi SE, Goldberg PA,
et al. Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the
updated Yale insulin infusion protocol. Endocr Pract. 2012;18:363370.17

only the absolute blood glucose level but also its rate of
change from prior values, as well as the current insulin
infusion rate. Ideally, the delineation of specific measures
for the transition to subcutaneous insulin that will ulti-
mately be required in most patients should be incorpo-
rated. These instructions would necessarily include the
initial doses and types and timing of insulin injections.
Wilson et al16 compared 12 published protocols in a
sample patient and reported great variability in target
ranges, thresholds for insulin infusion initiation, initial
infusion rates, and the frequency and intensity of ad-
justments, with markedly different glycemic outcomes
predicted. The insulin-infusion protocol in use at our
institution (Slide 6).17 in adult ICU patients recom-
mends starting the insulin infusion when 2 consecutive
blood glucose readings exceed 180 mg/dL (the target
range is 120 160 mg/dL). This target was chosen to be
slightly lower than the AACE-ADA target because ex-
perience with older versions of our protocol resulted in
mean blood glucose levels in the upper end of the target
ranges. We therefore believed that mean blood glucose
closer to 140 to 150 mg/dL (as intimated by the guide-
lines) was more desirable than one closer to 170 to 180
mg/dL. The infusion is adjusted in increments of 0.5
U/h. The initial infusion rate is preceded by a bolus,
with both calculated by dividing the baseline glucose
level by 100, rounded to the nearest 0.5 U. The blood
glucose is then checked every hour; the subsequent fre-
quency of monitoring can be decreased if 3 consecutive
findings are within target. In our published initial co-
hort of 90 patients, the protocol achieved a median
blood glucose of 150 mg/dL (range, 127180 mg/dL),
with a low rate of severe hypoglycemia (0.01% of glu-
cose measurements and 1.7% of patients). Notably,
these results compare favorably with those in the stan-
dard-therapy groups in the largest randomized trials of
intensive insulin therapy (mean of 2.1% from refer-
ences 10 12 and 18 20).
Glucose Control on General Medical-Surgical
Wards
Much less is known about the impact of acute gly-
cemic control in the non critical care settingwhich
encompasses the majority of all hospitalized patients.
As in the ICU, many observational studies have linked
hyperglycemia to adverse clinical outcomes,21,22 but
the same concerns regarding glucose being a marker as
opposed to a mediator of complications remain. For
example, Baker et al21 studied 433 patients with
acute exacerbations of chronic obstructive pulmo-
nary disease and found that the absolute risk for
adverse outcomes (death or prolonged stay) was in-
creased by 15% per 18-mg/dL increase in glucose
level. In the perioperative setting, Pomposelli et al22

May 2013 729

 Clinical Therapeutics
Postoperative Complications in Insulin Glargine + Insulin Glulisine vs SSI
30
P = 0.003
25
Outcome Frequency, %
24.3
20
15
10
8.6
5 P = NS
1.0 1.0
0
Composite Mortality
Slide 7. Results of the RABBIT 2-Surgery study. Overall decrease in post-operative complications was associated
with more intensive glucose control using a scheduled basal-bolus-correction insulin strategy. Reprinted
with permission from Umpierrez GE, Smiley D, Jacobs S, et al. Randomized study of basalbolus insulin
therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery
(RABBIT 2 Surgery). Diabetes Care. 2011;34:256 261.25
reported that in postoperative diabetic patients
whose glucose levels were 220 mg/dL, the infection
rate was 2.7-fold increased (exclusive of urinary
tract infections), with the risk for more serious in-
fections increased by 5.7-fold.
The only randomized studies in this area come from
Umpierrezs group.23 The RABBIT 2 study explored
the glycemic effects of scheduled long-acting and pre-
meal rapid-acting insulin (basal-bolus) versus con-
ventional sliding scales. In 130 insulin-naive patients
with a mean (SD) blood glucose level of 229 (6) mg/dL,
basal-bolus therapy (using the insulin analogues glargine
and glulisine) was more effective than was the sliding-
scale regimen.23 About two thirds of the patients treated
with glargine-glulisine achieved the blood glucose target
(140 mg/dL) versus about one third of patients in the
sliding-scale group. More insulin, however, was ulti-
mately used in the former (40 vs 15 total daily units) The
rate of hypoglycemia (defined as a blood glucose level
60 mg/dL) was similar between groups, and no blood
glucose levels 40 mg/dL were reported.
In the DEAN (Insulin Detemir Versus NPH Insulin
In Hospitalized Patients With Diabetes) study,24 the
insulin analogues detemir (basal) and aspart (prandial)
were compared with the more conventional human in-
sulins, neutral protamine Hagedorn (NPH) and regu-
lar human insulin. Here, the overall blood glucose tar-
get was achieved in 45% of the analogue-treated
patients and 48% of the human insulintreated pa-
730
Insulin Glargine + Insulin Glulisine SSI
P = 0.05 P = 0.10
10.3 10.3
P = 0.24
2.9 0.0 2.8 3.8
Wound Pneumonia Acute Renal
Infection Failure
tients (P 0.86). The difference in the rate of hypo-
glycemic episodes was not significantly different (33%
vs 25%; P 0.34). Taken together, these studies sug-
gest that tighter glycemic control can be achieved in
hospitalized patients with scheduled insulin ap-
proaches as opposed to sliding scales but that the types
of insulin used may not be crucial.
Finally, in RABBIT 2-Surgery (Randomized Study
of Basal-Bolus Insulin Therapy in the Inpatient Man-
agement of Patients with Type 2 Diabetes Undergoing
General Surgery),25 the basal-bolus program, again us-
ing glargine and glulisine, was compared to regular
insulin sliding scale in 211 patients undergoing general
surgery. There was an overall mean blood glucose ad-
vantage of 27 mg/dL in the basal-bolus group. A
variety of postoperative complications were tracked,
including wound infections, pneumonia, respiratory
failure, acute renal failure, and bacteremia. The pres-
ence of wound infections was significantly lower with
basal-bolus (2.9% of patients) than with sliding scale
(10.3%) (P 0.05), whereas differences in other compli-
cations between the 2 groups did not reach statistical
significance. However, when all of the complications
were assembled into a composite, a clear advantage to the
more intensive strategy was reported (8.6% vs 24.3% of
patients) (Slide 7).
The AACE-ADA15,26 inpatient consensus statement
also addressed the management of hyperglycemia out-
side of the ICU setting (Slide 5). The panel advised
Volume 35 Number 5
 M. Bogun and S.E. Inzucchi

Management of hyperglycemia in hospitalized patients

Non-ICU Patient with Hyperglycemia

T1DM, insulin-requiring T2DM, or new hyperglycemia T2DM on diet therapy or oral agents

NPO Eating NPO Eating

Basal insulin Basal insulin

(home dose or start 0.20.4 4 units/kg /day)
NPH Q12 h or
Detemir Q1224 h or
Glargine Q24 h
+ +
Correction insulin for BG>150 mg /dl
(graded scale of 14 units for each
50 mg/dl, based on insulin sensitivity)
Regular Q6 h
+ Glargine Q24 h
(home dose or start 0.20.4 units/kg /day)
NPH Q12 h or
Detemir Q1224 h or
Glargine Q24 h
Bolus (prandial) insulin
(home dose or start 0.050.1 units/kg /meal)
Lispro, Aspart, Glulisine or
Regular
Correction insulin for BG>150 mg /dl
(graded scale of 14 units for each 50 mg /dl,
based on insulin sensitivity)
Same type as & added to bolus insulin
May continue oral agents ONLY if no
D/C oral agents
contraindications & well controlled.
Correction insulin for BG>150 mg /dl
(graded scale of 14 units for each 50 mg /dl, If hyperglycemic or evidence of poor
based on weight & degree of control as outpatient, D/C oral agents
insulin resistance) (sensitizers can be continued) and
Begin basal insulin
Regular Q6 h
(start 0.20.4 units/kg /day)
NPH AM & PM (or HS) or
Detemir Q1224 h or
+
Bolus (prandial) insulin
(start 0.050.1 units/kg /day)
Lispro, Aspart, Glulisine or
Regular
+
Correction insulin for BG>150 mg /dl
(graded scale of 14 units for each
50 mg /dl, based on insulin sensitivity)
Same type as & added to bolus insulin

BLOOD GLUCOSE NOT CONTROLLED (consistently >140 mg /dl fasting, >180 mg /dl random)

Adjust basal insulin by ~1020%
Q12 days to achieve glucose target
Adjust correction insulin scale by 12
units per dose Q12 days if response
inadequate
Adjust basal insulin by ~1020%
Q12 days to achieve glucose target
Adjust bolus insulin by 12 units per
dose Q12 days to achieve target
Adjust correction insulin scale by
12 units per dose if response
inadequate
Add basal insulin Adjust basal insulin by ~1020%
(start 0.20.4 units/kg /day: adjust by Q12 days to achieve BG target
~1020% Q12 days to achieve BG target) Adjust bolus insulin by 12 units per
NPH Q12 h or dose Q12 days to achieve target
Detemir Q1224 h or Adjust correction insulin scale by
Glargine Q24 h
12 units per dose if response
Adjust correction insulin scale by
inadequate
12 units per dose if response
inadequate

Slide 8. Proposed strategy for managing hyperglycemia in non-critically ill hospitalized patients. Adapted with
permission from Inzucchi SE. Clinical practice. Management of hyperglycemia in the hospital setting.
N Engl J Med. 2006;355:19031911.

trying to maintain all glucose levels 180 mg/dL and
premeal glucose 140 mg/dL. The preferred approach
was that employing scheduled basal-nutritional (bo-
lus)-correction insulin instead of the still widely used
regular insulin sliding scales. At our institution, we en-
courage the routine use of such a strategy in those patients
who appear to require insulin therapy for 12 days. In
contrast, in short-term patients, the temporary use of cor-
rection insulin only is reasonable, especially if for those
with NPO status or if nutritional intake is tenuous.
We tend to avoid the use of oral antihyperglyce-
mic agents. Sulfonylureas may lead to hypoglycemia
if nutrition is interrupted. There is no inherent rea-
son that metformin could not be used, but given its
risk for lactic acidosis and the frequent complicating
features of hospitalized patients that might increase
this risk (renal failure, dehydration, severe heart fail-
ure, acidosis), it would appear best to avoid this
medication. Thiazolidinediones can be continued if
there are no concerns of heart failure, although an
interruption in therapy of a few days should not
appreciably alter glucose levels. Incretin-based ther-
apies (DPP-4 inhibitors and GLP-1 receptor ago-
nists) are ideally used in patients who are eating
because they target mainly postprandial glucose and
so should probably be avoided when nutritional intake
is forbidden or tentative. GLP-1 receptor agonists may
also result in nausea so are best avoided in this setting.
Some experts have proposed that, because these drug
classes are not associated with hypoglycemia and because
their activity appears to be in part related to the degree of
hyperglycemia, they may have a role in acutely ill pa-

May 2013 731

 Clinical Therapeutics
Discharge Planning
Be proactive! Start early (23 days before)
What can this patient handle at home?
Consider side effects, drug intolerances,
comorbidities, costs.
Rxs, supplies, appointments
Survival Skills
Outpatient follow-up is key.
Slide 9. Overview of hospital discharge planning
for patients with diabetes.
tients. Adequately powered, randomized clinical trials
will be needed.
See (Slide 8). for our general approach to managing
glucose in hospitalized but not non-critically ill diabetic
patients.
Transitioning to Outpatient Care
Discharge planning is an important part of in-hos-
pital diabetes management, especially in newly diag-
nosed patients or in those whose antihyperglycemic
regimen has been altered during the admission. Ideally,
this planning should begin several days before the an-
ticipated discharge and should carefully take into ac-
count whether the patient can successfully implement
the prescribed regimen and any accompanying comor-
bidities, prevalent contraindications, and anticipated
side effects. If the diagnosis of diabetes has already
been established, the level of control should be assessed
with adjustment of therapy, if necessary. If the disease
was newly identified during the hospitalization, the di-
agnosis should be confirmed. Here, the hospitalization
becomes an opportunity to educate and implement an
initial therapeutic plan. Finally, if stress hyperglycemia
resolves in-hospital or soon after discharge, then no
further action would be required other than routine
follow-up. Good communication with the patients
primary care clinician or endocrinologist is key to en-
sure a smooth transition postdischarge (Slide 9).
CONCLUSIONS
Hyperglycemia occurs frequently in the hospital, both
in patients with and without diabetes; its implications
may be more serious in the former. Inpatient hypergly-
cemia is a predictor of adverse outcomes including
mortality and is associated with increased length of
stay and costs. Intensive glucose management in the
732
ICU setting has led to improved outcomes in some sin-
gle-center studies, not all of which were randomized.
Yet other trials have questioned this benefit, and one
even suggested a mortality risk associated with inten-
sive insulin therapy. A rational synthesis of these data
would suggest that good (mid-100 mg/dL range) but
not necessarily stringent (110 mg/dL) glucose control
is the preferred approach in the ICU setting and is most
easily achieved through a validated intravenous insu-
lin-infusion protocol. On medical-surgical wards, a
premeal blood glucose target of 140 mg/dL is reason-
able and achievable in most patients. Physiologic, pro-
active insulin-replacement therapy (ie, the basal-bolus
correction approach) to prevent hyperglycemia is pre-
ferred to more conventional, retroactive approaches,
such as regular insulin sliding scales. Lastly, the dis-
charge planning should always ensure a smooth tran-
sition to outpatient care.
ACKNOWLEDGMENTS
Dr. Bogun drafted the manuscript, collected and inter-
preted the data. Dr. Inzucchi was responsible for the
critical review of the manuscript, collected and inter-
preted data and created the slides.
CONFLICTS OF INTEREST
Dr. Bogun has no conflicts of interest with regard to the
content of this article. Dr. Inzucchi has served as a
consultant/advisor to Merck, Boehringer Ingelheim,
Bristol Myers Squibb, and Novo Nordisk.
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