Chapter 35
Guidelines on Inpatient
Management of Hyperglycemia
Sukhminderjit Singh Bajwa, Manash P Baruah, Sanjay Kalra, Mukul Chandra Kapoor
ABSTRACT
Hospitalized diabetic patients pose numerous clinical challenges.
Sociobehavioral, economic, nutritional, racial, ethnic and other factors
make it difficult for application of hitherto published western guidelines
in India. The present chapter is an effort to bring forth the various
clinical challenges encountered during management of different
diabetic hospitalized populations and to formulate a set of patient and
physician friendly guidelines to control hyperglycemia in such patients.
Keywords: Diabetes; hyperglycemia; inpatients; insulin therapy; insulin
analogs
INTRODUCTION
Prolonged hospitalization and poorer outcome is a common
phenomenon amongst patients with diabetes mellitus (DM).1-3
There are inconsistent data regarding outcome of intensive control of
hyperglycemia amongst hospitalized patients.4,5 Such inconsistencies
create doubts regarding the adoption of precise therapeutic
interventions in indoor patients with hyperglycemia.
A large number of DM cases are diagnosed for the first time when
they get admitted for various indications, which may or may not be
related to DM. Although Indian data reveal that every sixth patient
admitted to hospital has diabetes, in reality the number may be
higher.6
NEED FOR INDIAN/ASIAN GUIDELINES
Although a number of guidelines on inpatient hyperglycemia
management have been published, they are not without
confounding biases involving nutritional status, level of awareness,
sociobehavioral, cultural and economic factors. Moreover, racial,
ethnic and genetic differences in insulin resistance and glucose and
lipid metabolism may limit the extrapolation of western guidelines
to an Indian population.7 There is an acute need for formulation
of user-friendly guidelines relevant in India and other developing
nations as well.
The guidelines delineated in this chapter are based upon
evidences derived from available literature. Initial core writing
group consisted of the authors of this article. Review of the draft
and grading of recommendations were done by a panel of experts
consisting of four endocrinologists, one internist, one pediatrician
and one obstetrician, each having at least a decade of experience.
Grading was based on a method suggested by Frid et al. (2010),8
which includes an ABC scale of recommendation and 123 scale for
supporting scientific evidence (Table 1). For each recommendation,
the postfixed capital letter in bold indicates how much weight a
recommendation should carry in daily practice, while the number
defines its degree of support in medical literature.
GUIDELINES FOR GLYCEMIC CONTROL
Hyperglycemia can have detrimental effects in both medical
and surgical hospitalized patients.9 So far as the management
of hyperglycemia is concerned, the hospitalized patients can be
categorized into two broad categories: (1) non-critically ill, and (2)
critically ill.
Non-critically Ill Patients
Compared to ICU patients, non-critical patients are less likely to
receive adequate attention for hyperglycemia per se. Physicians’
concerns for the management of primary pathology, lack of proper
monitoring facility and dedicated paramedical staff in general wards,
unsupervised dietary intake and fear of inducing hypoglycemia are
amongst the factors responsible. These factors are also responsible
for avoidance/delay in usage of insulin even in inpatients.
Hyperglycemia may lead to longer hospitalization, impaired wound
healing, and occasional risk of polyneuropathy, higher incidence of
systemic infections, urinary tract infections, acute renal failure and
increased cardiac morbidity.10,11
The targets proposed by American Diabetic Association (ADA)
for premeal blood glucose (BG) (< 140 mg/dL) and casual (random)
BG (< 180 mg/dL) are generally acceptable. Target can be lower than
this threshold in the following situations: (1) stable patients with
optimal glycemic control prior to admission, (2) postoperative ward
and gestational DM patients in a background of available adequately
trained staff for monitoring and treating hypoglycemia.12,13 Patients
who are able to eat adequately at regular intervals are right candidates
for subcutaneous (SC) insulin, because intravenous (IV) insulin
regimen is less flexible.
Sliding scale insulin (SSI), although quite popular, has been found
to be inferior to basal bolus (BB) regimen using rapid-acting analog
to fulfill prandial requirement and once daily long-acting analog to
fulfill the basal and supplemental need. Apart from achieving better
TABLE 1 │ Criteria for grading and rating recommendations8
Strength of A Strongly recommended
recommendation
B Recommended
C Unresolved issue
Scale of scientific 1 At least one randomized controlled study
support
2 At least one nonrandomized or
noncontrolled or epidemiologic study
3 Consensus expert opinion based on
extensive patient experience
 Section 5 Chapter 35  Guidelines on Inpatient Management of Hyperglycemia

BG control, the incidence of various infections, respiratory failure TABLE 3 │ Suggested protocol for insulin infusion in ICU
and acute renal failure is much lower in patients treated with insulin
analogs.14 Similarly, basal insulin analogs imparts better glycemic A. Preparation 50 units of regular insulin dissolved in 50 mL
normal saline (NS) in a 50 mL disposable
control in diabetic patients receiving enteral nutrition as compared syringe
to SSI.15
B. Mode of IV infusion with an electronic syringe pump/
Recommendations administration infusion pumps
• Premeal BG target should be 110–130 mg/dL, and postmeal target C. Primary target To maintain blood sugar level within a
should be 140–180 mg/dL. Targets should be less stringent for the predefined target 140 mg/dL
elderly and patients with significant medical comorbidity. Non- D. Control Blood sugar to be controlled gradually in case
critically ill inpatients on enteral nutrition should be preferably methodology of severe hyperglycemia by titrating the dose
managed with insulin [A1]. of IV insulin
• Basal insulin to cover the basal and correctional need, and E. Pre-requisites Initially 15–20 mL of solution should be
prandial rapid-acting insulin to cover the nutritional need are flushed through plastic tubing to saturate the
preferred choice. SSI is not recommended [A1]. insulin binding sites in the tubing
• Insulin analogs should be preferred in indoor patients as they are F. Targets Dose should be adjusted as per the levels of
associated with less hypoglycemia, better therapeutic outcomes, blood sugar
and are more flexible to use [A2].
G. Monitoring Either by capillary blood glucose or from the
venous site/central line
Critically Ill Patients
Glycemic control in critically ill patients is a unique challenge for TABLE 4 │ Titration of insulin dose according to blood glucose
both intensivist and endocrinologist, as these patients invariably (BG) levels
have multiorgan dysfunction. In spite of extensive data indicating
Blood glucose Dosage of insulin infusion
a relation between uncontrolled hyperglycemia and poor outcome
levels (mg/dL)
in critically ill, optimal glycemic targets are not precisely defined.
While evidence favors a tighter control in the range of 110–140 mg/ < 100 No insulin to be given
dL in surgical patients, a less aggressive target may suit medically ill 100–149 1–1.5 units/hour
patients.3,16 Such stringent targets can lead to severe hypoglycemia (< 150–199 2 units/hour
40 mg/dL), which is a cause of increase mortality in the critically ill.
A goal range of 140–180 mg/dL has been recently recommended and 200–249 2.5 units/hour
has been approved by most, if not all.9,16 250–299 3 units/hour
The only acceptable modality of treatment is continuous IV 300–349 3.5 units/hour
insulin infusion, which should be initiated when BG levels are
greater than 180 mg/dL (Tables 2 to 4). There are many IV insulin 350–399 4 units/hour
infusion regimens available, but those regimens are preferred, which For any further increase in BG, consulting endocrinologist/physician/
contain orders that take into account both current BG values and rate intensivist needs to decide the rate subjectively. If BG does not fall
of change of BG.5,17,18 more than 10%, insulin can be increased to 1.5 times the normal dose.
For basal, mealtime and correction doses, insulin analogs are If BG is < 50 mg/dL Administer 50 mL of dextrose (25 g), check
preferred over regular and neutral protamine hagedorn (NPH) blood sugar at 15 minutes and if blood glucose
increases to more than 100 mg/dL, start insulin
infusion after 1 hour
TABLE 2 │ Estimated initial dose of insulin in non-critically ill
hospitalized patients BG between 50 mg/ Infuse 50 mL dextrose (25 g) if hypoglycemia
dL and 75 mg/dL manifests clinically. If asymptomatic, give half
Total daily dose of Patient characteristics
dose of the above solution. Check blood sugar
insulin (units/kg
after 15 minutes and start insulin 1 hour after BG
body wt)
reaches > 100 mg/dL.
0.25 •  Geriatric patients
•  Renal or hepatic impairment
insulin as they have a predictable absorption mechanism and exhibit
•  On hemodialysis minimal pharmacokinetic variability. The incidence of hypoglycemia
0.5 •  Ordinary patients is significantly minimized if pre- and postprandial regular insulin is
1.0 •  Obesity and other insulin resistance state replaced by rapid-acting insulin analogs. Predictable duration of
action with minimal stacking effect enables the analogs to achieve
•  Glucocorticoid treatment euglycemia with minimal hypoglycemia.19
•  Severe infections
Recommendations
•  Coronary artery bypass graft (CABG)
• Maintain BG level at a range of 140–180 mg/dL for majority of
•  Total parenteral nutrition (TPN)
patients with medical morbidity, and 110–140 mg/dL for those
Calculation of subcutaneous dose of insulin in a 60 kg adult male with body mass with surgical morbidity [A1].
index (BMI) of 25 having moderate hyperglycemia: • Only IV insulin is recommended. Subcutaneous regimens with
  •  Total daily dose (TDD) = 0.5 units/kg body wt × 60 = 30 units premixed insulin, intermediate-acting or long-acting insulin and
  •  Basal insulin dose = 50% of TDD = 50% of 30 units = 15 units basal insulin SSI are not recommended [A1].
  •  Bolus insulin dose per meal = (50% of TDD)/3 = (50% of 30 units)/3 = 15/3
• Regular insulin or rapid-acting insulin analogs (aspart, lispro,
= 5 units of rapid-acting insulin before each meal
  •  Assessment of correctional scale insulin is based on TDD. For a patient glulisine) can be used as IV infusion. Glulisine should be used
with a TDD of 40 units, the low correctional scale should be ordered. only with normal saline [A2].
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 Diabetology Section 5

• Transition to subcutaneous insulin from IV insulin should have Flow chart 1: A simple algorithm of point of care monitoring of blood
an overlapping period of 1–2 hour. The overlap can be reduced to glucose in critically ill inpatients
15–30 min if rapid analogs are used [A2].

MONITORING OF BLOOD GLUCOSE

Technologies enabling bedside capillary blood glucose monitoring
with agility, rapidity and reasonable safety have revolutionized
inpatient management of hyperglycemia.20
Different approaches, such as venous, capillary blood and/or
plasma or whole blood have been used for precise measurement
of blood glucose.21 The question of accuracy of capillary vis-ä-vis
venous measurement has become redundant with the advent of
newer glucometer, which allows samples from either source to be
measured. The resulting advantages are minimal needle pricks (less
injury, less contamination, cost cutting) and elimination of factitious
reporting.22,23 However, to minimize errors, the glucometer readings
should always be tested and compared intermittently with laboratory
glucose values (internal quality control). A structured protocol-
based approach is of utmost importance (Flow chart 1). Continuous
glucose monitoring system (CGMS), which can monitor glucose
levels continuously up to 72 hours, may be useful in emergency
and intensive care units as it exhibits various glycemic trends and
patterns, help in timely detection of hypoglycemia and assesses
efficacy of ongoing therapy. However, the high cost, delay in obtaining
the results (after 72 hours) and limitation of real time display are a few
disadvantages.24 Capillary blood sample can be used except in situations like hypotension,
hypothermia, shock, use of vasoconstrictors and vasopressors where venous
Recommendations samples are preferred
• Mandatory BG testing for every patient on admission and at least
two readings in the next 24 hours to rule out hyperglycemia [A2]
.• Glycated hemoglobin should be obtained in patient with increase of BG is associated with 1–1.5 fold increase in odds ratio
hyperglycemia without prior history of DM and with persistent of bacteremia in neutropenic patients not on glucocorticoids.29
hyperglycemia of uncertain etiology. This test is unreliable in Administration of immunosuppressants in post-transplant period is
patients receiving massive blood transfusions [B2]. associated with hyperglycemia. As such, insulin requirement is much
• Point of care monitoring of blood glucose is to be done preferably higher in these patients. On the other hand, patient’s dietary changes
with capillary method. In cases of hypotension, hypothermia, may lead to sudden hypoglycemia. These factors warrant the use of
shock, use of vasoconstrictors and vasopressors, use venous insulin analogs due to their flexibility.30
sampling instead [A2].
• Initial monitoring should be done on an hourly basis. Interval Recommendations
of testing can be increased when three consecutive readings are • Tight glycemic control with insulin is advocated for a better
consistently around the target [B2]. surgical outcome, with targets of BG between 110 mg/dL and 140
• If logistics permit, CGMS should be used while monitoring mg/dL [A1].
glycemic status in critically ill patients [B2]. • Glucose and insulin should be given through separate IV routes.
• Postprandial testing should be included while monitoring Serum potassium should be monitored and maintained through
glycemia in patients on oral feed [C3]. supplementation [B2].
• Relatively minor procedure such as cataract surgery where
SPECIAL POPULATIONS patients need not remain nil per orally for prolonged periods may
continue on oral hypoglycemic agents if they are well controlled
Perioperative Management [A2].
Insulin is the preferred therapy in majority of surgical patients. The • The blood glucose target in post-transplant patients should be
most commonly used insulin regimens in India are GIK (glucose, similar to that of surgical inpatients. Analogs should be preferred
insulin and potassium) and variable insulin infusion regimens. The [A2].
cost associated with the pump infusion system prohibits the use
of such regimens in low resource settings. Alternatively, the use of Patients with Acute Myocardial Infarction
micro-drip set attached to dextrose solution containing therapeutic Hyperglycemia has been found to be associated with poor clinical
insulin and potassium is cost effective, and can be used in any setting outcome in acute myocardial infarction (AMI) patients.31 Whether
where monitoring of BG is possible as and when required. Adequate hyperglycemia is an indicator of the severity of AMI or it acts as a
control of hyperglycemia has shown to improve outcome in general mediator in causation of various complications associated with AMI
as well as special surgery wards.25-27 remains controversial. These controversies are further heightened by
Transplant surgery in diabetes is challenging as uncontrolled the fact that patients with hypoglycemia who suffer from acute MI
hyperglycemia is associated with increased cardiac morbidity, risk also have an adverse outcome.32,33 Tight glycemic control may not
of organ failure, acute graft versus host disease (grade II–IV) and contribute toward any increased mortality but it definitely reduces
increased risk of non-relapse-related mortality.28 Each 10 mg/dL the risk of complications associated with MI such as congestive

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 Section 5 Chapter 35  Guidelines on Inpatient Management of Hyperglycemia
cardiac failure and reinfarction.34 The efficacy of GIK regimen in
patients with acute AMI has remained inconclusive.35
Recommendations
• Hyperglycemia and hypoglycemia both should be avoided in
patients with AMI to decrease morbidity and mortality [A1].
• Optimal glycemic control insulin, preferably analogs during and
after the episode, decreases the risk of complications associated
with AMI [A2].
Patients on Glucocorticoid Therapy
Due to sustained hyperglycemia especially during post-prandial
period, susceptible glucocorticoid users can be treated with
titration of meal-time insulin dose.36,37 The variable sensitivity and
requirement of the insulin mandates monitoring of BG for 48 hours in
patients receiving high-dose glucocorticoid therapy so as to prevent
any episode of hyperglycemia or hypoglycemia.38 Basal bolus insulin
in the patient can be adjusted on the basis of correctional insulin
requirements. An increment of 20% of intermediate- or long-acting
insulin doses is considered safe to control hyperglycemia.38,39 Due
to inadequate quality evidence in medical literature, formulating
the best apprach to control hyperglycemia in patients on high-dose
glucocorticoid therapy remains a difficult task.
Recommendations
• Regular and sustained monitoring of BG should be done in
patients on high dose of glucocorticoid therapy [A1].
• Treatment naïve patients developing hyperglycemia after
glucocorticoid initiation should be managed with insulin [A2].
• For patients already on insulin, 20% increment in total daily
insulin dose at time of high-dose glucocorticoid initiation is a
reasonable step [B2].
Patients on Enteral Nutrition
The control of hyperglycemia is challenging in patients receiving
enteral nutrition as glycemic levels show marked variability with
type and duration of enteral nutrition (i.e. Ryles tube or gastrostomy
tube). Basal insulin may exert hypoglycemic effects on sudden
discontinuation of enteral nutrition.40,41 Basal insulin analogs
control hyperglycemia, in combination with SSI, without any higher
incidence of hypoglycemia as compared to SSI alone, as the latter
regimen is associated with additional requirement of intermediate-
acting insulin in 48% cases.15
Recommendations
• Insulin analogs should be preferred to control hyper­glycemia in
indoor patients on enteral nutrition [A2].
• Basal plus multiple SC prandial boluses are to be preferred over
SSI [A1].
Patients Receiving Parenteral Nutrition
Parenteral nutrition can be extremely detrimental to critically ill
diabetic patients as the large amount of glucose in these solutions
results in severe hyperglycemia. The uncontrolled hyperglycemia is
responsible for higher incidence of compli­cations and mortality in
this subset of population.42
Recommendations
• Intravenous insulin is the preferred treatment for control of
hyperglycemia in patients receiving parenteral nutrition [A1].
• Glucose targets should be based on the severity of under­lying
illness [A1].
Peripartum Control of Hyperglycemia
The effect of placental hormones, growth factors and cytokines
increases insulin resistance during pregnancy, and this significantly
enhances insulin requirements. Constant vigil for sudden onset of
metabolic complications like maternal ketoacidosis during labor
and neonatal hypoglycemia is essential and has to be managed
appropriately. Insulin dose should be titrated on an individual basis
as parturient shows wide variability in insulin resistance after 14
weeks of gestation.43
Recommendations
• Insulin is the preferred therapy in pregnancy complicated by
diabetes [A1].
• Rapid-acting insulin analogs—aspart and lispro are preferred for
use in pregnancy. Detemir is a preferred choice as basal insulin
[A2].
• Patients in active labor should be on glucose, IV insulin plus
potassium infusion to prevent hypokalemia, hypoglycemia as
well as ketosis [A1].
• Incremental insulin dose is required for pregnant ladies receiving
long-acting glucocorticoid for fetal maturity [B2].
Critically Ill Pediatric Patients
Management of hyperglycemia in pediatric patients is challenging
especially among critically sick patients.44 Factors such as longer
duration of hyperglycemia and higher peak BG (> 180 mg/dL) can lead
to prolonged hospitalization, increased nosocomial infections and
3.5 fold increase in sepsis-related mortality risks.44-47 Management
of hyperglycemia in ICU with IV insulin infusion is definitely a safer
option in pediatric patients.48 The target of BG (110–150 mg/dL)
should be modest, and insulin should be used judiciously to avoid
hypoglycemia and ketosis.49 The physiological insulin resistance
during pubertal growth may be perceived as increased insulin
requirement in this age group.50 To this end, the use of insulin analogs
(both basal and rapid) looks quite promising.
Recommendations
• Insulin is the preferred therapy in pediatric ICU with optimal BG
target of 110–150 mg/dL [A2].
• Insulin analogs are preferred over conventional insulin.
Recommended age limit is greater than 2 years for aspart, greater
than 3 years for lispro, greater than 4 years for glulisine, greater
than 2 years for detemir, and greater than 6 years for glargine [A2].
Transition to Outdoor Management
Discharge and outdoor management of patients with diabetes
should be done only after prior stabilization of blood glucose levels.
Physicians should be aware of the onset, peak and the effective
duration of each type of insulin before writing out the treatment
plan (Table 5). It is prodent to follow a practival plan of switching
over to SC insulin based on the most recent IV insulin requirement,
rather than doing it arbitrarily with inconsistent results (Table 6).
The patient should be provided a simplified treatment plan including
drug regime and its appropriate use, BG monitoring schedule,
hypoglycemic symptoms and their management, and contact
number of primary care physician whom they can contact during any
major complaint or emer­gency. Patients should be shifted to more
convenient insulin regimes, such as premixed insulin twice daily,
if possible, before discharge from hospital, and the concordance of
meals and SC insulin should be ensured. They should be monitored
on this regime for a few days in hospital if possible, and the first
follow-up should be done within 10–14 days time period.51
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 Diabetology Section 5

TABLE 5 │ Onset, peak and total effective duration of action of among various disciplines. Appropriate use of insulin and insulin
various preparations of insulin analogs using IV or SC regimes as required to target euglycemia
ensures better therapeutic outcomes. Along with this, training of
Insulin preparation Onset Peak Effective
(hour) (hour) duration
health workers, education of support staff, use of simple protocols,
(hour) auditing of mortality and morbidity statistics and a good feedback
system are essential for the successful management of hyperglycemia
Short-acting subcutaneous
in low resource health set-up.
Lispro < 0.25 0.5–1.5 3–4
Aspart < 0.25 0.5–1.5 3–4 ACKNOWLEDGMENTS
Glulisine < 0.25 0.5–1.5 3–4 The authors are grateful to Dr Ganpathi Bantwal, Dr Mathew John,
Dr Rakesh K Sahay, Dr AG Unnikrishnan, Dr Raman Setty, Dr
Regular 0.5–1.0 2–3 4–6
Inderpreet Sohi, Dr Sukhwinder Kaur Bajwa for their critical inputs
Long-acting while formulating and grading the evidences.
Neutral protamine hagedorn 1–4 6–10 10–16
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