Internal Medicine / Hospital Medicine

Board Review Manual

Statement of
Editorial Purpose
The Internal Medicine/Hospital Medicine Board
Review Manual is a study guide for trainees
and practicing physicians preparing for board
examinations in internal medicine and hos
pital medicine. Each manual reviews a topic
essential to the current practice of internal
medicine and hospital medicine.

PUBLISHING STAFF

Management of Inpatient
Hyperglycemia
Contributor:
Lowell R. Schmeltz, MD
Assistant Professor, Oakland University William
Beaumont School of Medicine, Royal Oak, MI; Chief
of Endocrinology, Detroit Medical Center Huron
Valley-Sinai Hospital, Commerce, MI; Associated
Endocrinologists, PC and Endocrine Hospital
Consultants, PC, West Bloomfield, MI

PRESIDENT, Group PUBLISHER

Bruce M. White
Senior EDITOR

Robert Litchkofski
executive vice president

Barbara T. White
executive director
of operations

Jean M. Gaul

Table of Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Hyperglycemia and Patient Outcomes. . . . . . . . . 3
AACE/ADA Guidelines for Optimal Glycemic
Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Hyperglycemia Treatment Options in the Hospital
Setting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

NOTE FROM THE PUBLISHER:

This publication has been developed with
out involvement of or review by the Amer
ican Board of Internal Medicine.

www.turner-white.com

Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Internal Medicine / Hospital Medicine Volume 14, Part 4 

Management of Inpatient Hyperglycemia

Internal Medicine/Hospital Medicine

Board Review Manual

Management of Inpatient Hyperglycemia

Lowell R. Schmeltz, MD

Introduction
Over the past decade, hyperglycemia in the
hospitalized patient has gained tremendous attention due to its association with increased mortality
and inpatient complications as well as its negative economic impact. Likewise, hypoglycemia is
associated with poor outcomes and remains the
limiting factor in controlling hyperglycemia. Even
the experienced clinician is challenged every day
at achieving the glycemic target, and a multitude
of variables besides food intake and insulin dosing
exist. Improvements in glycemic control throughout
the hospital stay are associated with decreases
in short- and long-term risk of mortality, inpatient
complications, and hospital lengths of stay.1 Financial benefits of glycemic control are significant, not
just in reducing direct hospital costs by reducing
length of stay, but also in decreasing hospital readmission rates.24 Hospital care accounts for half of
the health care costs for patients with diabetes.5
Conservative estimates of the incidence of diabetes in adult hospitalized patients range from 12%
to 26%.6 The incidence of hyperglycemia in nondiabetic patients at the time of hospital admission
is estimated to be 12%, which translates into 1 out

of every 8 hospital admissions. Stress hyperglycemia (in the nondiabetic patient) historically was felt
to be part of the natural course of acute illness and
not treated unless glucose levels exceeded 200
mg/dL or the patient was symptomatic.7 However,
we now know that stress hyperglycemia has been
associated with longer hospital stays, higher rates
of intensive care unit (ICU) admission, greater need
for rehabilitation services at the time of discharge,
and higher mortality rates.8 In the largest review of
hospital glycemic control, which included 576 hospitals and over 49 million blood glucose readings
from 3.5 million patients, the average ICU glucose
level was 166 mg/dL and the average non-ICU
glucose level was 167 mg/dL.9 The analysis further
revealed that one-third of both ICU and non-ICU
patient-days were characterized by hyperglycemia
(> 180 mg/dL) and 6% of patient-days in each
group met criteria for hypoglycemia (< 70 mg/dL).
The need to improve the treatment of hyperglycemia in hospitals is increasingly being recognized,
but still has yet to be universally accepted.9
The link between hyperglycemia and adverse
hospital outcomes is multifactorial. Elevated blood
glucose concentrations produce a proinflammatory
cytokine predominance,10 leading to a multitude of

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 Hospital Physician Board Review Manual

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Management of Inpatient Hyperglycemia

downstream effects, including capillary basement
membrane thickening, impaired phagocytosis and
immunity, oxidative stress, abnormal lipid metabolism, decreased vascular contractility, increased
platelet adhesiveness, increased concentrations
of coagulation factors, and increased C-reactive
protein levels.8 Contributing factors to hyperglycemia include elevations in stress-related hormones
(growth hormone, catecholamines, cortisol, glucagon), pharmacologic agents,11 enteral and total
parenteral nutrition,12,13 and glucocorticoid therapy.14
As a result, a glycemic control plan should be in
place for all hospitalized patients with hyperglycemia.

hyperglycemia and patient outcomes

Historically, diabetes is associated with higher
perioperative mortality,15 deep sternal wound infections,16 postoperative strokes, and longer length of
hospital stays.17 Tighter glucose control has been
beneficial in a variety of patient settings including
acute myocardial infarction,18 strokes,19 communityacquired pneumonia,20 and chronic obstructive
pulmonary disease exacerbations, and in non-ICU
postsurgical settings such as renal transplantation,21 total joint arthroplasty,22 and colorectal surgery.23 Morbidity and mortality are correlated with
the presence and degree of hyperglycemia in the
postoperative period24 and are independent of a
prior diagnosis of diabetes.
Interventional outcomes studies have shown
benefits in inpatient morbidity and mortality from
intensive inpatient hyperglycemia management,
especially in individuals without a prior history of
diabetes.2531 In Van den Berghes landmark study
in a single Belgian surgical ICU, tight glycemic control was associated with a 34% reduction in hospital
mortality, 46% reduction in sepsis, 41% reduction in
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renal impairment requiring dialysis, 50% reduction

in blood transfusions, and 44% reduction in the incidence of ICU polyneuropathy, as compared with
standard hyperglycemia management.25 Based on
these results, the standard of care in the glucose
management of ICU patients began to change, but
the optimal glycemic target remained controversial
in different patient populations because the results
of van den Berghes study were not reproducible.
The largest randomized ICU trial assessing intensive glycemic control, the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose
Algorithm Regulation (NICE-SUGAR) study, reported higher mortality and hypoglycemia rates in
ICU patients treated with intensive glycemic control
(80110 mg/dL) compared to less tight glycemic
control (glucose <180 mg/dL).32 The conventional
group in NICE-SUGAR, however, required insulin
69% of the time in order to achieve the target
glucose below 180 mg/dL, indicating a continued
need for insulin therapy in the majority of critically
ill patients, just with a less intensive glucose target
range. The goal target range for all critically ill patients remains controversial, but likely is population
specific and should be individualized based on the
clinical situation, training of ICU personnel with insulin protocols, and risk of hypoglycemia.
Glycemic variability has emerged as an additional component affecting hyperglycemia outcomes.
In the outpatient setting, wider glucose fluctuations
(defined as the amplitude from peak to trough
in glucose) corresponds to an increased risk of
diabetic microvascular complications in patients
with diabetes.33 Krinsley previously identified the
near-linear relationship between ICU mortality and
mean glucose.34 Further data from his mixed medical, cardiac, and surgical ICU shows glucose variability within each subset of mean glucose (even
within the euglycemic range) is also an indicator

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Management of Inpatient Hyperglycemia

Table 1. Glycemic Goals in the Hospital
Patient Type

Glycemic Goals

Preferred Method of Insulin Administration

Critically ill patients

140180 mg/dL

Non-critically ill patients

Preprandial blood glucose
Maximum blood glucose

<140 mg/dL
<180 mg/dL

Intravenous insulin infusion

Initiate insulin at glucose >180 mg/dL
Maintain glucose 140180 mg/dL
Glucose <110 or >180 mg/dL not recommended
Subcutaneous insulin
Basal insulin
Nutritional or mealtime insulin
Correctional dose insulin

Adapted from Moghissi ES, Kortykowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract 2009;15:35369.

of ICU mortality. In patients with the best glycemic control (mean glucose 7099 mg/dL), those
with the largest glycemic variability had a fivefold
increase in mortality compared to patients with
the least glycemic variability.34 A larger European
ICU study had similar results.35 Outside the ICU,
glycemic variability is also a predictor of mortality
in patients on parenteral nutrition,36 but not in the
general medical ward population. In non-ICU surgical patients, glycemic variability is associated with
postoperative mortality and hospital complications
in hyperglycemic patients without known diabetes,
but not in patients with diabetes undergoing general surgery.37

AACE/ADA Guidelines For Optimal

Glycemic Control
The American Association of Clinical Endocrinologists (AACE) and the American Diabetes
Association (ADA) have developed guidelines for
optimal glycemic control in the hospital setting.38,39
These recommendations can be summarized as
follows: 1) identify elevated blood glucose in all
hospitalized patients, 2) establish a multidisciplinary team approach to diabetes management in
 Hospital Physician Board Review Manual

all hospitals, 3) implement structured protocols for

aggressive control of blood glucose in ICUs and
other hospital settings, 4) create educational programs for all hospital personnel caring for people
with diabetes, and 5) plan for a smooth transition
to outpatient care with appropriate diabetes management.40,41 The AACE/ADA guidelines provide
structure around which institutions can develop
protocols that achieve blood glucose goals yet
allow for individualization of algorithms and policies
to fit with the hospitals culture and environment. In
May 2009, AACE/ADA revised their inpatient glycemic targets to 140 to 180 mg/dL for ICU patients,
to below 140 mg/dL for preprandial glucose levels
in non-ICU patients, and to below 180 mg/dL for all
random glucose levels (Table 1).

Hyperglycemia Treatment Options in

the Hospital Setting
CASE PATIENT

A 68-year-old Caucasian man with a past

medical history significant for type 2 diabetes, hypertension, and hypercholesterolemia is
admitted with an acute myocardial infarction. Blood
glucose on admission is 254 mg/dL. His home diawww.turner-white.com

Management of Inpatient Hyperglycemia

betes regimen is metformin 1000 mg twice daily and
glyburide 10 mg twice daily. His weight is 104 kg
with a body mass index of 33.2 kg/m2. Most recent
hemoglobin A1c was 10.4% and fasting blood sugars
at home have ranged from 180 to 300 mg/dL. His
creatinine is 1.7 mg/dL. The patient is admitted to
the cardiac ICU after percutaneous coronary intervention. His blood glucose is currently 202 mg/dL.
You are called by the nurse to write admission orders for his diabetes management.
What is the optimal diabetes regimen to use
during this patients hospital stay?
Upon admission to the hospital, hyperglycemic patients should be managed using either
intravenous (IV) or subcutaneous (SC) insulin
algorithms. Insulin therapy should be effective
(reach acceptable glucose targets in the shortest
duration of time) and safe (with minimal incidence
of hypoglycemia). Patients with hyperglycemia
should be on a carbohydrate consistent diet (if
eating), and glucose monitoring should be ordered
before each meal and at bedtime. Alternatively,
glucose monitoring should be ordered every 4 to
6 hours in patients who are NPO, on tube feeding,
or on total parenteral nutrition (TPN). All patients
with hyperglycemia should have their glycosylated hemoglobin (A1C) checked on admission to
help differentiate between long-term or relatively
new-onset hyperglycemia. The Joint Commission
recommends obtaining an A1C level during the
hospital stay if one is not documented in the past
60 days to identify previously unrecognized diabetes or to help guide optimization of the outpatient
diabetes regimen if the A1C is elevated. Recently,
an international expert committee recommended
that an A1C of 6.5% or higher indicates a diagnosis
of diabetes.42
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Most inpatient diabetes algorithms recommend

discontinuing oral antidiabetic drugs (OADs) and
initiating insulin analog therapy. OADs should be
discontinued on admission for various reasons.
Insulin secretagogues, such as sulfonylureas and
glitinides (nateglinide, repaglinide), are associated
with an increased risk of hypoglycemia. Metformin
should not be used for inpatients because of the
increased risk in changes in renal function and
impairment (due to volume shifts, medications, or
contrast-induced nephropathy). Thiazolidinediones
(rosiglitazone, pioglitazone) are insulin sensitizers
that can increase circulating plasma volume by 6%
to 7%, and therefore should not be used in patients
with edema or heart failure. Incretin-based agents
(sitagliptin, saxagliptin, linagliptin, exenatide, liraglutide, and pramlintide) may increase the risk of
gastrointestinal adverse effects, which may slow
the recovery of a hospitalized patient, although
they have not been frequently studied in the inpatient setting. IV infusion of a glucagon-like peptide
1 agonist was recently compared to IV insulin
infusions in non-critically ill patients and controlled
blood sugars with less hypoglycemia.43 This proof
of concept study raises the hope for noninsulinbased mechanisms of glycemic control to be further investigated.
Insulin

Insulin is the preferred agent for glycemic control

in hospitalized patients. The pharmacodynamic
properties of insulin allow it to be adapted to the
changing physiology of the sick patient, it can be
easily titrated, and it does not have a dosage threshold. Furthermore, insulin has a rapid onset of action,
minimal side effects except for hypoglycemia, and
minimal drug interactions. Unfortunately, insulin also
is considered a high-risk drug with regards to medication safety and administration errors.

Internal Medicine / Hospital Medicine Volume 14, Part 4 

Management of Inpatient Hyperglycemia

Table 2. Insulins Used in Hospitalized Patients
Generic (Brand)
Rapid-acting insulins
Insulin lispro (Humalog)
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Short-acting insulins
Regular insulin
(Humulin R, Novolin R)
Intermediate-acting insulins
NPH insulin
(Novolin N, Humulin N)
Long-acting insulins
Insulin detemir (Levemir)
Insulin glargine (Lantus)

Onset/Duration

IV/SC Use

Recommended Use in Hospital

515 min/35 hr
515 min/35 hr
515 min/35 hr

SC
SC, IV*
SC, IV*

15 min before or immediately after meal

510 min before meal
15 min before or 20 min after starting meal

3060 min/68 hr
(longer with U-500 or
renal insufficiency)

SC, IV

Preferred for insulin drips; avoid for postprandial use; do not use sliding scale

24 hr/812 hr
(longer with renal
insufficiency)

SC

Can be used as a twice-daily substitute for

basal insulin regimen

38 hr/1624 hr
24 hr/24 hr

SC
SC

Preferred for basal insulin use

Preferred for basal insulin use

IV = intravenous; SC = subcutaneous.
*Insulin analogs have no benefit over regular insulin for IV infusions.
Adapted with permission from Schmeltz LR. Safe insulin use in the hospital setting. Hosp Pract 2009:37:5159.

The Society of Hospital Medicine has developed a workbook to guide hospitals in creating
safe and effective glycemic control plans. The
workbook includes multiple successful, published
inpatient insulin protocols. Common themes in
these protocols are the utilization of regular insulin
for continuous insulin infusion and a basal/bolus
SC insulin regimen including a long-acting insulin
given once daily (insulin glargine or detemir) and
prandial doses of a rapid-acting insulin (insulin
aspart, glulisine, or lispro).4447 The ideal insulin
protocol will help attain the glucose target range
in a timely manner, effectively treat all degrees of
hyperglycemia and do so with minimal glycemic
variation, and minimize the risk of hypoglycemia;
it should also be easy for nurses to carry out in a
timely fashion.48
Insulin analogs are preferred for basal, mealtime, and correction doses instead of human
 Hospital Physician Board Review Manual

insulins (regular and NPH), because analogs

have a more predictable absorption and action
profile and less pharmacokinetic fluctuation in
patients with renal insufficiency. High doses of
regular insulin not only have a greater peak effect than lower doses, but also have a longer duration of action that can lead to overlap of insulin
doses (known as insulin stacking) and increase
the risk of a hypoglycemic event. The duration
of action of rapid-acting insulin analogs is predictable at both low and high doses, thereby
decreasing the risk of insulin stacking. Insulin
analogs have a more consistent pharmacokinetic and pharmacodynamic profile (less interindividual and intraindividual variability),49,50 so it
is easier to predict the effect the dose will have
on an individuals blood glucose concentration.
Table 2 describes the types of insulin recommended for hospital use.51,52
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Management of Inpatient Hyperglycemia

Continuous infusion of regular insulin is suggested for critically ill ICU patients, pre- and postoperative patients, peripartum women with hyperglycemia, patients with severe hyperglycemia with
metabolic decompensation (diabetic ketoacidosis
and hyperosmolar non-ketotic states), and any
patient in whom tight glycemic control is clinically
indicated. Insulin given intravenously has a half-life
of 7 to 8 minutes, and therefore reaches a new
steady state in less than 1 hour after any titration.
Most insulin infusion algorithms suggest glucose
monitoring every 1 to 2 hours until reaching the
target glucose range. Some insulin protocols include a bolus dose of IV insulin when the drip
rate is increased to help reach steady state more
quickly.44 A review of IV insulin infusion protocols
that adjusted the insulin drip rate based on the rate
of change of glucose (not just the current glucose
level) showed that such protocols were more effective.53 Paper-based and computer-based insulin
infusion algorithms are available to guide clinicians
to achieve optimal glycemic control.44,54,55
CASE CONTINUED

In the ICU, the patient is placed on a

continuous insulin infusion with a drip rate
averaging 2 units/hr. He is stable after his cardiac
intervention. In the past 24 hours, his glucose has
ranged from 100 to 150 mg/dL without hypoglycemia. He is tolerating an oral diet. He is ready for
transfer from the ICU to the general medical ward
for further monitoring.
What is the optimal diabetes regimen for this
patient upon leaving the ICU?
DOSING OF INSULIN

Many clinicians struggle with the appropriate

dosing of insulin when admitting patients to the
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hospital or transferring patients out of the ICU.

The key concept in dosing of SC insulin is estimating the patients total daily dose of insulin (TDD).
The TDD can be derived in many ways such as
measurement of 24-hour insulin requirements on
an insulin drip, review of the patients pre-hospital
insulin regimen (if they were on insulin prior to admission), or using a weight-based calculation.
Converting from IV to SC Insulin

Conversion from IV to SC insulin commonly

occurs when the critical illness resolves and the
patient is extubated, off vasopressors, and ready
to start eating or has achieved a stable tube-feed
rate. When the patient is being converted from
an IV insulin drip, the drip rate is used as a guide
to determine total daily insulin requirements. The
insulin drip rate over the preceding 6 hours is averaged to obtain a stable hourly rate. The average
hourly rate is multiplied by 24 hours to calculate
TDD required. The basal insulin dose ordered is
60% to 80% of the TDD and the prandial insulin dose for each meal is 10% of the TDD. The
prandial insulin dose is adjusted accordingly as
the patients appetite improves. The proportion of
insulin given for prandial dosing is substantially
less because these patients are generally consuming only a clear liquid diet initially with a reduced caloric content. The insulin infusion should
be continued for 4 hours after the first injection
of basal insulin is given (if insulin glargine or
detemir; 2 hours if NPH insulin). Practical necessities sometimes outweigh physiologic reasoning
in that conversion from IV to SC insulin often
coincides in time with transfer of the patient out
of the ICU, with the result that the insulin infusion
is simply stopped without an overlap period. In
this scenario, a conversion dose of a rapid-acting
insulin (10% of TDD) can be given simultaneously

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Management of Inpatient Hyperglycemia

with the basal insulin and the insulin infusion can
be discontinued without an overlap period.56
Basal-Bolus Insulin Regimens

For all non-critically ill patients, a basal/bolus

insulin regimen is the preferred method of glycemic control (Table 3). Basal insulin suppresses
hepatic gluconeogenesis between meals and
overnight. During illness, basal insulin requirements rise with any physical stress including
surgery, infection, infarction, or fever. For patients
who are eating, a scheduled mealtime insulin
dose with a rapid-acting insulin analog helps prevent the glucose from rising from carbohydrate
intake. Whether eating or not, when blood sugars
are outside the glycemic target range, a correctional dose of rapid-acting insulin can be given to
lower the glucose.
Hospitalized patients have unpredictable eating
and diagnostic testing schedules and thus are
more susceptible to an insulin-food dyssynchronythe risk of hypoglycemia increases if insulin
peaks before the patient has eaten or consumed
enough carbohydrates; hyperglycemia results if
the insulin peak is insufficient to meet glucose
intake or metabolic stress needs. Rapid-acting
insulin analogs can be given immediately before
or up to 20 minutes following food consumption and thus are more flexible and less likely to
cause hypoglycemia.57 Furthermore, if the patient
is not eating reliably, mealtime insulin doses can
be adjusted based on actual carbohydrate intake
(such as reducing the dose 50% if half the food
is consumed).
For patients who are on insulin at home, continuing their home insulin dosing is not always the
appropriate inpatient regimen. Many patients eat
a significantly different diet at home compared
to the carbohydrate-consistent diet given in the
 Hospital Physician Board Review Manual

Table 3. Summary of Recommendations for Insulin Regimens

in Different Patient Situations
ICU or severe hyperglycemia
Eating
NPO/Tube feeds
TPN (if insulin in TPN)
TPN (if insulin not in TPN)

Insulin drip while critically ill

Basal + Prandial + Correction scale
Basal + Correction scale
Correction scale only
Basal + Correction scale

ICU = intensive care unit; TPN = total parenteral nutrition.

hospital. Also, medications and acute physical

stress from their illness often increase their insulin
requirements. The key is to anticipate the change
in insulin requirements based on what is known
about their home glucose control, which requires
a brief assessment of their diabetic behaviors prior
to admission and an understanding the physiologic
changes that medication, surgery, or illness will
have on their insulin requirements.
Premixed insulins are generally not recommended for use in the hospital setting, as there
is an increased risk of hypoglycemia in patients
with variable oral intake. Some hospitals have
pharmacy personnel perform a simple conversion
from premixed insulin to separate long-acting and
rapid-acting insulin analogs upon admission to the
hospital by multiplying the total daily home dose
of premixed insulin by the basal/bolus ratio (either
70/30 or 75/25). This allows basal and premeal
insulins to be ordered separately; thus, mealtime
insulin can be administered in a timely manner with
the patients meal or held if the patient is not eating. Subsequently, at the time of discharge, these
patients can be converted back to their premixed
insulin if appropriate.
For patients on OADs at home and who are insulin naive, TDD insulin requirements can be estimated with a weight-based algorithm (Table 4).5860
In 2 randomized controlled studies comparwww.turner-white.com

Management of Inpatient Hyperglycemia

Table 4. Weight-Based Estimation of the Total Daily Insulin
Requirement
0.3 units/kg
[Umpierrez58]
0.4 units/kg
[Umpierrez58]
0.5 units/kg
0.6 units/kg [Magaji and
Johnston60]

Age > 70 years

Creatinine > 2.0 mg/dL
Patient with diabetes + glucose
< 200 mg/dL on admission
Patient with diabetes + glucose
> 200 mg/dL on admission
Obesity
Insulin resistant
Glucocorticoids

ing basal-bolus insulin to regular insulin sliding

scales, 0.5 units/kg daily appears to be a safe
and effective dosing estimate.58,59 In patients with
renal dysfunction (creatinine above 2.0 mg/dL) or
age greater than 70 years, 0.3 units/kg/day is recommended (patients with a creatinine > 3 mg/dL
were excluded from these trials). Using the TDD
estimate, 50% of the insulin requirement is ordered as basal insulin (long-acting insulin analog
such as glargine or detemir) with the other 50%
divided into 3 mealtime or prandial doses using
a rapid-acting insulin (such as lispro, aspart, or
glulisine).
Subsequently, blood sugar values should be
reviewed on a daily basis, with a 10% increase
in the basal insulin doses for morning glucoses
ranging between 140 and 180 mg/dL, and a
20% increase in basal insulin doses for glucoses over 180 mg/dL consistently. Alternatively, if
the glucose levels are below the target range, a
decrease in the basal insulin dose by 10% is appropriate for glucose levels between 80 and 100
mg/dL, and a 20% decrease in the basal insulin
dose is appropriate for glucose values below 80
mg/dL or in the hypoglycemic range. Pre-lunch
and pre-dinner glucose values will be heavily dependent on the mealtime insulin dose at the prior
meal and the amount of food eaten. Appropriate
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adjustments to mealtime insulin doses should be

made as well.
Regular insulin should be avoided for SC postprandial blood glucose correction and should not be
used as a sliding-scale regimen. Numerous studies
over the past 50 years show that sliding-scale insulin (SSI) alone is not effective for inpatient glycemic
control (Figure) and more recently has been associated with increased inpatient mortality.61 SSI does
not allow for basal or mealtime insulin requirements,
grossly underestimating total daily insulin requirements. Admittedly, SSI may be appropriate when
used for a short duration (less than 24 to 48 hours)
as a measurement of total daily insulin requirement.
Appropriate clinical situations include elevated admission glucose in nondiabetic patients, individuals
beginning corticosteroid therapy, or with initiation of
enteral or parenteral nutrition.62 Measuring insulin
requirements for 24 hours allows for an assessment
of the TDD that can then be converted to a basalbolus insulin regimen.
Steroids

Steroid-induced hyperglycemia affects all patients, and not just those with preexisting diabetes. Glucose monitoring is recommended for the
first 48 hours of high-dose glucocorticoid therapy
to identify those individuals in which insulin therapy will be necessary to maintain near-normal
glycemia.63 Although optimal insulin dosing for
patients on steroids is unknown, increasing insulin doses approximately 20% is generally safe.64
Blood sugar values should be reviewed on a daily
basis, with adjustment of the insulin regimen
as needed. As steroid doses are tapered, it is
critically important to anticipate the decrease in
insulin requirements rather than wait for a hypoglycemic episode to occur to prompt a reduction
in insulin doses.

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Management of Inpatient Hyperglycemia

Sliding Scale Only

Glucose-Unit Base Meter-RALS
600
500

Basal/Bolus Insulin

mg/dL

400

300
200
100
0
1/16/2007 1/20/2007 1/22/2007 1/24/2007 1/26/2007 1/28/2007 1/30/2007 2/01/2007 2/03/2007 2/05/2007

Figure. Example of a patient on a sliding scale only insulin regimen for the first few days following admission with high mean glucose
and large glycemic variability. When switched to a basal/bolus insulin regimen, mean glucose gradually decreased and glycemic
variability was significantly less. RALS = remote automated laboratory system. (Adapted with permission from Schmeltz LR. Safe
insulin use in the hospital setting. Hosp Pract 2009;37(1):55.)

Tube Feeds/TPN

Patients on enteral or parenteral nutrition often

have hyperglycemia induced by the constant
carbohydrate administration. For patients on
enteral feeds, reduced carbohydrate and modified fat content formulas result in lower glucose
levels and these formulas should be used.65 In
TPN patients, hyperglycemia is associated with
significant adverse outcomes.66 Insulin dosing
in TPN (usually with regular insulin) can be initiated at 0.1 units for every gram of carbohydrates
10 Hospital Physician Board Review Manual

in the TPN solution. Insulin dosing for enteral

feeding can use the weight-based estimation
of TDD, administering basal insulin at 50% of
the TDD. The optimal glycemic range should be
slightly higher (in the 140180 mg/dL range) in
these groups, as measured blood sugars are
not fasting in nature. Since discrete meals are
not being consumed, using basal insulin with
correction dose insulin every 4 to 6 hours is the
optimal insulin regimen (every 4 hours if using
a rapid-acting insulin for correction doses, and
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Management of Inpatient Hyperglycemia

every 6 hours if using regular insulin for correction doses). Unanticipated discontinuation of the
carbohydrates can occur if the tube feed is accidentally removed or if the TPN is discontinued.67
Adding a 10% dextrose solution at the same
rate as the tube feeding or TPN infusion can
prevent hypoglycemia in these situations. Insulin
is usually administered in the TPN solution, so
discontinuation of the TPN includes discontinuation of insulin therapy and a dextrose replacement solution is only needed if SQ basal insulin
is being used.
Understanding insulin physiology allows the
clinician to tailor an appropriate insulin regimen in
a variety of clinical scenarios. Table 5 reviews the
initiation of insulin regimens in a variety of different
patient situations.
Minimizing Hypoglycemia

Hypoglycemia is the limiting factor to aggressively

normalizing blood glucose levels in all patients. Hypoglycemia is an independent predictor of hospital
mortality.68 Spontaneous hypoglycemic events (not
induced by insulin) are associated with significantly
higher mortality rates when compared to iatrogenic
or insulin-induced hypoglycemic events.69 In the
review of 576 hospitals, 6.3% of ICU patient-days
had a hypoglycemic event (defined as a glucose <
70 mg/dL) and 5.7% of non-ICU patient-days had
a hypoglycemic event.9 In a study of over 100,000
inpatient admissions in patients with diabetes,
patients who experienced hypoglycemic episodes
had longer hospital stays, a 7% higher risk of inpatient mortality, a 39% increase in hospital costs,
and a 58% increased likelihood of discharge to a
skilled nursing facility.70
A root cause analysis of over 1000 hypoglycemic
events at a large academic medical center found
that 67% of the documented hypoglycemic epiwww.turner-white.com

sodes were associated with a change in diet or enteral or parenteral rate within the previous 24 hours
(unpublished data, Northwestern Medical Center,
Chicago, IL). Additional factors that increase the
risk of hypoglycemia include a lack of coordination
between feeding and insulin administration (which
can lead to mistiming of insulin action), insufficient
frequency of blood glucose testing, orders not
clearly or uniformly written, and failure to adjust
insulin requirements in patients with advanced
age, renal failure, liver disease, or changing clinical status. With the addition of a nursing electronic
medical recordbased hypoglycemia event form to
document each event, the incidence of hypoglycemia was decreased 50%.
Preventing and minimizing the incidence and
severity of hypoglycemia is possible with the
use of standardized insulin protocols, hypoglycemia protocols, and use of insulin analogs.7075
Hypoglycemia protocols should be nurse-driven76
and supported by point-of-care testing (POCT).
Organizations should have a method of tracking hypoglycemic events and assessing adverse
reactions related to insulin use, and should also
monitor the use of 50% dextrose and glucagon as
triggers and perform ongoing quality monitoring of
hypoglycemic events. Ongoing review of insulin-related errors and near misses should be conducted
at the hospital level.77
The Role of Point-of-Care Testing

POCT is a convenient method of measuring glucose levels in a timely manner to allow

for rapid insulin titration and clinical decision
making. Glucometers, however, may not be the
most accurate and reliable method to monitor
glucose. An international standard is currently
under development that recommends accuracy
of 20 mg/dL for glucose values under 100

Internal Medicine / Hospital Medicine Volume 14, Part 4 11

Management of Inpatient Hyperglycemia

Table 5. Clinical Scenarios of Appropriate Insulin Regimens in Different Patient Situations
50-year-old male with type 2 diabetes mellitus (DM) admitted with pneumonia. Home diabetes regimen is insulin glargine 30 units
daily, insulin aspart 10 units before each meal. He is ordered an American Diabetes Association (ADA) 1800kcal diet.
Capillary blood glucose monitoring: QAC (before meals) and QHS (at bedtime)
Order hypoglycemia protocol for glucose < 70 mg/dL
Order hemoglobin A1C
Basal insulin: Order insulin glargine 30 units every 24 hr
Mealtime insulin: Order insulin aspart 10 units before each meal
Correction insulin scale: Moderate dose insulin aspart correction scale QAC (before meals) and QHS (at bedtime) if appropriate (use moderate scale since total daily insulin dose is 60 units)
66-year-old female with type 2 DM admitted with a small bowel obstruction. Home diabetes regimen is insulin glargine 30 units daily,
insulin aspart 10 units before each meal. She is made NPO on admission.
Capillary blood glucose monitoring: every 4 hr or every 6 hr
Order hypoglycemia protocol for glucose < 70 mg/dL
Order hemoglobin A1C
Basal insulin: Order insulin glargine 30 units every 24 hr
Mealtime insulin: Hold insulin aspart 10 units before meals as she will not be eating
Correction insulin scale: Order moderate dose insulin aspart correction scale every 4 hr or every 6 hr (since total daily insulin dose is 60 units)
72-year-old female with type 2 DM admitted with chest pain. Home diabetes regimen is insulin 70/30 25 units twice daily. She is made
NPO on admission for a stress test.
Capillary blood glucose monitoring: every 4 hr or every 6 hr
Order hypoglycemia protocol for glucose < 70 mg/dL
Order hemoglobin A1C
Calculate basal insulin requirements: 50 units per day x 70% basal component of insulin 70/30 = 35 units
Basal insulin: Order insulin glargine 35 units every 24 hr
Mealtime insulin: Hold mealtime insulin as she will not be eating
Correction insulin scale: Order moderate dose insulin aspart correction scale every 4 hr or every 6 hr (since total daily insulin dose at home
is 50 units)
68-year-old male with type 2 DM admitted with a diabetic foot ulcer. Home diabetes regimen is metformin 1000 mg twice daily and glyburide 10 mg twice daily. He is ordered an ADA 1800kcal diet. He weighs 100 kg.
Capillary blood glucose monitoring: QAC (before meals) and QHS (at bedtime)
Order hypoglycemia protocol for glucose < 70 mg/dL
Order hemoglobin A1C.
Stop all oral antihyperglycemic agents on admission
Calculate insulin requirement = 100 kg x 0.5 units/kg/day = 50 units/day
Basal insulin = 50% of total daily insulin requirement = insulin glargine 25 units every 24 hr
Mealtime insulin = 50% of total daily insulin requirement divided into 3 equal mealtime doses = insulin aspart 8 units before each meal
Correction insulin scale: Order moderate dose insulin aspart correction scale QAC (before meals) and QHS (at bedtime) if appropriate (use
moderate scale since total daily insulin dose is 50 units)

mg/dL and 20% for higher glucose values

quite a large variation for those aiming for
a narrow therapeutic window.78 Common rea12 Hospital Physician Board Review Manual

sons for erroneous POCT blood glucose readingssuch as improper handling of the test
strips and equipment leading to analytic error
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Management of Inpatient Hyperglycemia

underscore that care must be used in following
the manufacturers instructions regarding appropriate quality-control measures. POCT blood glucose results may be inaccurate in patients with
extremes in hematocrit, glucose, PO2 values,
and body temperature.79 Specimens from arterial blood have higher glucose concentrations
than venous samples; glucose levels in plasma
are generally 10% to 15% higher than glucose
measurements in whole blood. Capillary specimens may not be representative of central blood
glucose concentrations in patients with shock or
diabetic ketoacidosis. Certain medications may
interact with the POCT equipment and produce
a faulty reading (eg, maltose- and fructosecontaining medications can interfere with meters
utilizing the dehydrogenase method). In these
cases, POCT should be used with caution. In
general, it is a good idea to confirm unexpected
POCT blood glucose results with a specimen
sent to a central laboratory for analysis.
Continuous glucose monitoring systems have
been developed for the outpatient setting, but none
has been shown to be effective in the hospital.
Given the limitations of POCT, the need for more
accurate and real-time glucose monitoring is apparent. Development of SQ, transdermal, and IV
glucose monitoring is underway at various phases
of study.8082
CASE CONTINUED

On the general medical ward, the patient

is prescribed insulin glargine 25 units at
bedtime and insulin glulisine 8 units before each
meal with a correction insulin scale. His blood
glucose levels have ranged from 88 to 164 mg/dL
over the past 24 hours. The patients cardiac status
has been optimized and he is ready for discharge.
Overall, he is satisfied with his blood sugars durwww.turner-white.com

ing his hospital stay and he hopes to maintain this

level of glucose control at home.
DISCHARGE

Effective discharge planning for patients with hyperglycemia should begin at the time of admission.
During the hospitalization, one should assess any
new physical limitations (eg, blindness, amputation,
debilitation), the patients socioeconomic factors (insurance coverage, family support), access to followup care, and any learning barriers (changes in cognition or dexterity as well as language and culture).
The A1c measurement will help guide the clinician
on recommendations for a home diabetes regimen. If the A1c is in an acceptable range, less than
7%, then returning to the previous home diabetes
regimen may be appropriate assuming there are no
new contraindications to the diabetes medications
(eg, an elevated creatinine in a patient previously
on metformin). If the A1c is elevated, then there is a
chance to intervene and advance the patients diabetes therapy. It is important for the patient to understand the big picture of outpatient diabetes control,
specifically the prevention of cardiovascular events
including heart attack and stroke and the prevention of diabetic microvascular complications. If the
patient is new to insulin, the clinician should explain
the importance of timing of blood sugar monitoring
and insulin administration, review hypoglycemia
symptoms and treatment, review the criteria for
calling their physician, and consider a referral to an
outpatient diabetes educator for follow-up instruction. Involving family members in the insulin education may increase compliance and understanding of
the new insulin regimen. Communicating the new
regimen to the primary physician is critical in case
problems arise after hospital discharge.
For nondiabetic patients who have steroid- or
stress-induced hyperglycemia during their hospital

Internal Medicine / Hospital Medicine Volume 14, Part 4 13

Management of Inpatient Hyperglycemia

stay, no definite data exists to indicate an increased
risk of developing diabetes in the future. These
individuals should have a fasting glucose and A1c
measured 6 to 12 weeks after the hospital stay to
make sure their hyperglycemia does not persist.

4.
5.
6.

Summary
Insulin is preferred therapy for treating all hospitalized patients with hyperglycemia, independent of
their diabetes status. With recent outcomes studies
like NICE-SUGAR, we have transitioned from the
era of tight glycemic control to one of less-tight
glycemic control focusing intensely on the safety
and efficacy of the glycemic control plan. Although
optimal target glucose ranges remain controversial,
the consensus is that glycemic control is important
and hospitals should continue to manage blood
sugars with insulin. Those hospitals that are successful with lower glycemic targets may choose to
continue current practice; others may choose higher
glycemic targets to balance the risk of hypoglycemic
events and ensure patient safety.
BOARD REVIEW QUESTIONS
Test your knowledge of this topic.
Go to www.turner-white.com and select Internal Medicine
from the drop-down menu of specialties.

7.
8.
9.
10.

11.
12.
13.

14.

15.

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