Diabetes Mellitus and Hyperglycemia

Management in the Hospitalized Patient

Patricia A. Mackey, FNP-BC, BC-ADM, and Michael D. Whitaker, MD, FRCPC

ABSTRACT
Diabetes mellitus and hyperglycemia are common in hospitalized patients.
Uncontrolled hyperglycemia during hospitalization is associated with poor outcomes.
A glucose goal of 140-180 mg/dL is recommended. Scheduled subcutaneous insulin
with basal, prandial, and correction components is preferred for treating diabetes in
nonecritically ill patients. The pharmacodynamics of insulins differ, and the type of
insulin used should match daily glucose excursions. Varying hospital settings may
warrant using a particular insulin type to achieve optimal glucose control. Herein we
describe approaches to address hyperglycemia in the hospitalized patient on the basis of
insulin pharmacodynamic profiles.

Keywords: basal-bolus insulin, correction insulin, diabetes mellitus, hospitalized

patient, hyperglycemia
Ó 2015 Elsevier, Inc. All rights reserved.

O
ptimal glucose control is a challenge for
hospitalized patients. Proper treatment of
hyperglycemia while avoiding hypoglyce-
mia should be the goal of multidisciplinary teams
(endocrinologists, hospitalists, nurses, surgeons,
advanced-level practitioners, pharmacists, and inten-
sivists) working together to provide care for the pa-
tient with diabetes mellitus or hyperglycemia in the
hospital setting. Hyperglycemia in hospitalized pa-
tients can represent previously known diabetes, un-
diagnosed diabetes, or illness-related hyperglycemia.
Hemoglobin A1c values
6.5% suggest that diabetes
preceded the hospitalization.1 Numerous studies have
indicated that targeted glucose control in the hospital
has been shown to improve clinical outcomes; the
association between hyperglycemia in hospitalized
patients (with or without diabetes) and the increased
risk for morbidity and mortality have been well
established.2
Challenges encountered in the hospital setting
can make controlling glucose difficult. These chal-
lenges include a new diagnosis of diabetes; infection;
a more rigid diet; inactivity; decreased appetite;
variable renal and hepatic status; an unpredictable
schedule of testing, procedures, and surgical in-
terventions; the use of hyperglycemic-provoking
agents (glucocorticoids, octreotide, catecholamines,
and calcineurin inhibitors); the administration of
contrast agents with certain tests; enteral and total
parenteral nutrition (TPN); and the stress induced by
the hospitalization itself.
GLYCEMIC GOALS
Although several organizations have issued guide-
lines for outpatient glucose management, no
guidelines or protocols have been formulated for
inpatient management. Maintaining glucose levels
between 140 and 180 mg/dL is recommended for
the majority of hospitalized patients.1 Individualized
goals for younger patients without comorbidities
(with previous stable glucose control before
admission), or for the elderly, terminally ill, or those
with extensive comorbidities (eg, congestive heart
failure, cirrhosis, and renal failure), have been
established for use in the outpatient setting, but no
recommendations exist for inpatient glycemic goals
for these different groups.
Standardized glycemic goals for certain pop-
ulations of hospitalized patients have suggested that
targets < 110 mg/dL are not recommended and may
lead to poor outcomes, especially in critically ill
patients.1 Recent studies failed to show a significant

www.npjournal.org The Journal for Nurse Practitioners - JNP 531

improvement in mortality with intensive glycemic
control.3,4
Hyperglycemia in the hospital (blood glucose
> 140 mg/dL) can increase the risk of infections, delay
wound healing, and possibly prolong the length of
hospital stay. Hyperglycemia has been associated with
endothelial dysfunction, oxidative stress, acidosis,
caloric and protein losses, electrolyte imbalances,
impairment of neutrophil function, and potential
exacerbation of myocardial and cerebral ischemia.2
Conversely, hypoglycemia (blood glucose < 70
mg/dL), if brief and mild, may not have long-term
sequelae, but severe hypoglycemia (blood glucose
< 40 mg/dL) could provoke neurologic effects or
seizures, or could trigger arrhythmias or other cardiac
events.5 Possible causes of hypoglycemia in the
hospital include variability in insulin sensitivity related
to the underlying illness, changes in counterregulatory
hormonal responses to procedures or illnesses,
prolonged nothing-by-mouth (NPO) status, variable
doses of dextrose fluids or glucocorticoid therapy,
unexpected decreases in food intake or emesis,
interruption of enteral or parenteral nutrition, sepsis,
concurrent malignancy, use of quinolone antibiotics,
or worsening of hepatic or renal function. Providers
should be proactive in reducing insulin doses in
such settings.
MANAGEMENT OF HYPERGLYCEMIA
Oral Agents
Oral antidiabetic agents used in the hospital are
difficult to titrate, have not been studied for safety
and efficacy in hospitalized patients, and may pre-
dispose patients to hypoglycemia. Also, the use of non-
insulin injectable medications, such as the glucagon-
like peptide 1 analogs, may be contraindicated
in many inpatient settings. Sulfonylureas act by
increasing insulin release from islet cells in the
pancreas, which can lead to severe, prolonged hy-
poglycemia, particularly in elderly patients and pa-
tients with poor appetite or impaired renal function.6
Metformin, which suppresses glucose production by
the liver, should not be used in patients who have
decompensated heart failure, renal insufficiency, or
chronic pulmonary disease.1 Diagnostic tests, such as
computed tomography scans, that involve IV contrast
dye, can put the patient taking metformin at risk of
532 The Journal for Nurse Practitioners - JNP
renal failure or lactic acidosis. Despite being discontinued
during the hospital stay, oral agents and non-insulin
injectable medications may be resumed at discharge
in patients with a history of good glycemic control
before hospitalization, who are stable, and have no
contraindications.
Insulin
For optimal glucose control, scheduled subcutaneous
insulin with basal, prandial, and correction compo-
nents is the preferred treatment method for the
nonecritically ill patient in the hospital.1 There is a
paucity of accepted insulin algorithms to facilitate
inpatient glucose management. Prudent treatment of
hyperglycemia while avoiding hypoglycemia is the
primary goal.
With normal endogenous insulin secretion, the
body’s insulin production increases after each meal
with consumption of carbohydrates, and then nor-
malizes between meals, bringing serum glucose
levels back to within a normal range (Figure, part A).
Even with prolonged fasting, blood glucose rarely falls
below 50-60 mg/dL, due to hepatic glycogenolysis
and subsequent gluconeogenesis. Moreover,
endogenous insulin secretion is present to metabolize
hepatic glucose production. Understanding this
relationship and trying to mimic a natural, physiologic
response requires an understanding of insulin
pharmacodynamics. Using rapid-acting insulin at
mealtimes and a long-acting basal insulin (programs
with multiple daily injections) best mimics the natural
physiologic responses of the body (Figure, part B). The
pharmacodynamics of types of insulin have differences
(Table). In the hospital setting, with many extraneous
variables, the appropriate types and timing of insulin
doses are paramount, as is consideration of the
circumstances and the current clinical condition of
the patient.
Basal-Bolus Insulin Therapy
Basal insulin therapy. Long-acting basal insulins,
such as glargine, detemir, or intermediate-acting
neutral protamine Hagedorn insulin (NPH), are
usually given once or twice daily. Basal insulin
prevents ketosis in insulinopenic patients (patients
with type 1 diabetes mellitus or post-pancreatectomy
diabetes) and, if used properly, will manage fasting
Volume 11, Issue 5, May 2015
Figure. (A) Normal glucose-insulin postprandial excursions. The normal postprandial blood glucose excursions in
fasting glucose levels over a 24-hour period (solid blue line), with concurrent endogenous insulin responses (red
dotted line) are shown. Hepatic glucose production sustains glycemia during the fasting state. (B) Multiple daily
injections of insulin. The example shows a subcutaneous basal-bolus insulin regimen matching meal intake and
fasting glucose hepatic production. Glargine and aspart are used as insulin examples, but detemir could be
substituted for glargine, and any other rapid-acting analog could be substituted for aspart. (C) Insulin action and
duration. The example shows a postprandial glucose excursion and superimposed insulin action compares rapid-
acting aspart insulin to short-acting regular insulin.

hepatic glucose production. Fasting glucose levels are
the best indicator of an adequate basal insulin dose.
Basal insulin is usually administered at bedtime HS,
but administering it in the morning in patients with
renal failure can prevent nocturnal hypoglycemia.6 It
may be used twice daily in patients receiving
continuous nutrition (parenteral or continuous tube
feedings), or for enhanced absorption in those
requiring large doses (> 100 units) of basal insulin
daily. Because of its pharmacodynamic profile
(Table), NPH has limited use in the hospital setting.
However, it can be effective in hospitalized patients
receiving nocturnal tube feedings. Compared with
the long-acting analogs glargine or detemir, NPH
has been associated with an increased risk of
hypoglycemia. Combination insulins, such as
Novolin or Humulin 70/30 mixed insulin (70%
isophane insulin human suspension [intermediate-
acting basal insulin] and 30% regular insulin human
[short-acting insulin]), can be administered at the
start of tube feeding in the hospital, or twice daily
before breakfast and before dinner in hospitalized
patients who are eating. A disadvantage of using
combination premixed insulins is their lack of dosing
flexibility. They could be an option at discharge for
patients who are on an insulin program of multiple
daily injections and who prefer 2 rather than 4
daily insulin injections, or for patients who have
limited financial resources, medical insurance, and
prescription drug coverage. Combination premixed
insulins cost less than the analog mixes (Humalog
Mix 75/25 and NovoLog Mix 70/30), or other
analog insulins (lispro, aspart, glulisine, detemir,
and glargine).
Bolus insulin therapy. Bolus insulin (also
referred to as prandial or nutrition insulin) is usually
given just before meals or at mealtimes (AC), or at
the time of bolus tube feedings. The rapid-acting

www.npjournal.org The Journal for Nurse Practitioners - JNP 533

Table. Insulin Pharmacodynamicsa
Type of Insulin Trade Name
Ultrafast-acting Technosphere insulin
(Afrezza) (inhaled)b
Rapid-acting Lispro (Humalog)b
Aspart (NovoLog)b
Glulisine (Apidra)b
Short-acting Regular
Intermediate-acting NPH
b
Long-acting Detemir (Levemir)
Glargine (Lantus)b
h ¼ hours; min ¼ minutes; NPH ¼ neutral protamine Hagedorn.
a
The metabolic effect of various insulins (peaks, onsets, and durations) are shown. Ranges account for patient variability.
b
Insulin analog.
insulin analogs are preferred (aspart, glulisine, or
lispro) over short-acting regular insulin because of
their quicker onset and shorter duration and because
they more closely match mealtime glucose excursions
(Figure, part C). Prandial insulin analogs can be dosed
by the amount of carbohydrates eaten, and they can
be given before or immediately after the meal for
patients who may not be sure before the meal how
much food they will actually consume (eg, patients
with nausea or gastroparesis). In the hospital setting,
fingerstick point-of-care capillary blood glucose
testing is usually ordered at mealtimes and at bedtime.
Scheduled prandial insulin is ordered for mealtimes to
cover the carbohydrates consumed.
CORRECTION INSULIN THERAPY
Correction insulin (also known as sliding scale
insulin) is administered to correct a glucose level
above a certain target. Correction scales based on
insulin sensitivity can be mild (for frail, elderly,
thin, insulin-sensitive patients, or for patients with
renal insufficiency), moderate (for most patients),
aggressive (for obese, insulin-resistant patients on
high-dose steroids), or individually provider-
directed, based on the particular situation of the
individual patient. Correction insulin, if needed, is
usually added to the scheduled prandial dose for a
single injection. Sometimes, in the hospital,
correction insulin is also administered at HS.
Correction insulin is intended to lower high
glucose levels, not to cover nutritional glucose
intake.7 Using correction insulin alone in
534 The Journal for Nurse Practitioners - JNP
Onset Peak Duration
Instant 15-20 min 2-3 h
10-15 min 45-60 min 3-5 h
30-60 min 2-4 h 4-8 h
1-2 h 6-10 h 20-24 h
2h Small 24 h
2h None 24 h
the hospital setting is neither recommended nor
effective.8 A physiologic insulin regimen is indeed
superior to a standardized insulin sliding scale for
management of hyperglycemia in hospitalized
patients. Using correction insulin alone, without
basal and prandial insulin components, puts
patients with type 1 diabetes and insulin deficiency
at risk for ketoacidosis, and it may be detrimental
to glucose control. It is a reactive approach to
treating hyperglycemia, rather than a proactive or
an anticipatory approach. As a result of previous
findings, many hospitals are not using correction
insulin as a stand-alone therapy for treating diabetes
and hyperglycemia in inpatients, and they instead
are using a basal-bolus insulin regimen to improve
inpatient glucose control.3,9 When correction scales
are used alone for several days (one size fits all),
glycemic control is often not assessed, which may
result in wide swings in glucose levels throughout
the hospitalization period.
Correction scale insulin can, however, be useful in
the first 24-48 hours of hospitalization. It can serve as
an insulin doseefinding strategy before an individu-
ally appropriate basal-bolus program can be deter-
mined and started.
A general guideline for calculating insulin
sensitivity to select an appropriate correction scale
is to use the “Rule of 1500,” which calculates the
insulin sensitivity factor for regular insulin. The
sensitivity factor shows how far blood sugar will
decrease per unit of regular insulin: 1500 divided by
the total daily dose (TDD) of insulin ¼ correction
Volume 11, Issue 5, May 2015
factor, which equals the interval in a correction
scale (also known as the insulin sensitivity).10
The “Rule of 1800” was later developed to show
the sensitivity factor per unit of analog insulin
(NovoLog, Humalog, or Apidra) because blood sugar
will decrease faster with analog insulins. This rule is
1800 divided by the TDD of insulin ¼ correction
factor/insulin sensitivity.
As an example, when using the rule of 1500 with
40 units of TDD insulin per day (eg, NPH þ regu-
lar), the correction factor would be 1500 / 40 or 38.
When using an analog insulin, and the rule of 1800
with 40 units of TDD (eg, NPH þ NovoLog), the
correction factor would be 1800 / 40 or 45.
TPN AND INSULIN
Correction insulin is usually administered intermit-
tently (4-6 times daily), if necessary, for patients
who are NPO on continuous tube feedings, or on
parenteral nutrition or TPN. Checking the capillary
glucose of patients on continuous TPN therapy every
4 hours, and using correction insulin if necessary at
those times, may result in better glucose control. This
is because of the loss of incretin effect with the use of
TPN (IV nutrition bypasses the intestinal regulators
of glucose metabolism), which is also often high in
carbohydrates. Instead of a separate basal insulin in-
jection administered concurrently with the TPN, the
total daily basal requirement of insulin, once estab-
lished, can be incorporated as short-acting regular
insulin into the TPN bag.
When initially adding insulin to the TPN bag for
the first time, a good starting point would be to add
0.1 unit of regular insulin for every gram of carbo-
hydrate in the bag.7 Any scheduled basal insulin that
was received by the patient in the 24 hours before
TPN was initiated can be incorporated into the TPN
bag as well (as regular insulin). The scheduled
subcutaneous basal insulin (eg, detemir, NPH, or
glargine) is then discontinued. The correction scale
insulin is continued (rapid-acting or short-acting) to
supplement the insulin in the TPN bag. The TDD of
insulin incorporated into the TPN bag is adjusted
daily, depending on the additional rapid-acting or
short-acting correction insulin used by the patient
during the previous 24-hour period.
www.npjournal.org
INITIAL START OF INSULIN
When an inpatient (who is not transitioning off an
insulin drip) is started for the first time on a basal-
bolus insulin regimen in the hospital, a weight-based
calculation can be used as a starting point. The
TDD ¼ patient weight (in kilograms)  0.5, with
50% of the dose being the basal requirement and 50%
of the dose being the prandial requirement.
To start a 220-pound (100-kg) patient who is
eating well on a basal-bolus insulin regimen, multiply
weight (in kilograms) by 0.5 (100  0.5). The result
is 50 units as the TDD of insulin. Then divide 50
units by 2, and one half of the TDD is the basal in-
sulin requirement (25 units) and the other half is the
prandial requirement (25 units). The prandial doses
should be ordered as 8 units with each meal, that is, 3
times a day. If that same patient were to be made
NPO, the scheduled prandial insulin should not be
ordered; the patient would have just the basal insulin
(25 units). Order an appropriate correction scale us-
ing rapid-acting insulin for AC and HS to be
administered concomitantly with the scheduled
prandial and basal insulins. Because of the current
limited length of stay of hospitalized patients, basal
insulin should be titrated daily by 10%-20% until the
fasting glucose is at goal. The prandial insulins should
also be titrated daily by 10%-20% until the pre-meal
glucoses are at goal range, and bedtime glucose is
< 180 mg/dL (preferably < 140 mg/dL), to optimize
glucose control during the hospitalization. Using
every opportunity throughout the patient’s hospital-
ization to make an insulin adjustment, if necessary,
will help to determine the most accurate insulin doses
at the time of discharge.
IV INSULIN INFUSIONS
IV insulin infusions are often used in the intensive
care unit to attain optimal glucose control in patients
with glucose levels > 180 mg/dL. Indications for use
of an IV insulin infusion occur in patients with un-
controlled blood glucose (> 400 mg/dL), diabetic
ketoacidosis, and hyperosmolar hyperglycemic non-
ketotic syndrome; posteorgan transplant patients on
high-dose corticosteroids in the immediate post-
operative period; postemyocardial infarct patients or
those having cardiac surgery; patients admitted on
The Journal for Nurse Practitioners - JNP 535
insulin pumps undergoing certain types of surgery
involving high doses of steroids (the insulin pump is
disconnected); and post-pancreatectomy patients to
determine insulin requirements in the immediate
postoperative period. IV insulin infusions require
hourly blood glucose testing and rate adjustment, if
necessary. They can be effective at keeping glucose
levels in the targeted ranges, and they allow for easy
titration of the insulin. IV insulin algorithms are
standardized guidelines for dose adjustment that are
based on the glucose level. Appropriate doses may
depend on the degree of illness, body weight, or
medications. Many hospitals use predetermined
algorithms, from mild (for frail, elderly, type 1 dia-
betic, post-pancreatectomy, or postebariatric surgery
patients) to more aggressive (for morbidly obese
or insulin-resistant patients or those on high doses
of glucocorticoids). Some facilities are using Glu-
commander (Glytec LLC) as a method of maintaining
IV glucose control. It is a safe, computer-directed
algorithm that has been studied extensively, and it
can be effective throughout the hospital, not just in
the intensive care unit.11
If the patient is clinically stable, has reached a
steady state of glucose control, is recovering from
critical illness, is beginning to eat regular meals, or is
transferred to a general nursing unit, he or she may be
ready for the transition from IV to subcutaneous
insulin. All patients with type 1 or type 2 diabetes
mellitus should be transitioned to subcutaneous long-
acting or intermediate-acting insulin at least 2 hours
before discontinuation of the IV insulin infusion.
This overlap between the discontinuation of the in-
sulin drip and administration of subcutaneous basal
insulin is to prevent recurrent hyperglycemia during
the transition period.
When transitioning a stable inpatient off an insulin
drip who has not been eating while on the drip, it is
reasonable to add up the hourly infusion rates (per
hour) over the previous 6 hours, and then multiply
by 4 to calculate the TDD of basal insulin require-
ment. The premise is that, because of the steady state
of IV insulin infusion over the previous 6 hours, this
value will probably best reflect the current clinical
state and insulin requirements of the patient for a
24-hour period. Another option would be to take
the average hourly rate over the previous 6 hours and
536 The Journal for Nurse Practitioners - JNP
multiply that by 24 to obtain the TDD of basal
insulin. Provider discretion and clinical judgment
can dictate whether the TDD could be reduced by
10%-20%, depending on the clinical situation of the
patient (eg, concomitant medication dose changes,
nutritional status, and severity of illness). One half of
the TDD of basal insulin is administered subcutane-
ously at the time of transition off the insulin drip, and
the other half is administered at bedtime that eve-
ning. The insulin drip is typically discontinued 2
hours after the first subcutaneous injection of basal
insulin. If the patient was eating while on the insulin
infusion, the TDD value should be divided into
50% prandial insulin and 50% basal insulin doses. The
50% total prandial dose value would then be divided
by 3 for a scheduled dose of insulin at each mealtime
of the day. A correction insulin scale is also ordered
for AC and HS. If the patient has not been eating
100% of their meals but has been eating some while
on the IV insulin infusion, reducing the amount of
scheduled prandial insulin by 10%-20% would be
reasonable.
Consider this example of transitioning a stable
patient who has been NPO from an IV insulin
infusion to subcutaneous insulin. If the patient has
been receiving a stable rate of 4 units of insulin per
hour over the previous 6 hours, multiply 6 (hours)
 4 (units/hour) ¼ 24 units, and then multiply 24
(units)  4 ¼ 96 units to determine the total daily
(24-hour) basal insulin requirement. Consider
ordering about 80% of this amount if the patient is
not as acutely ill and if doses are to be decreased for
vasopressors, steroids, or any other medications that
would affect glucose levels. If ordering 80% of the
total basal insulin requirement, then 38 units of basal
insulin would be ordered once (80% of 96 units ¼ 77
units, then divided by 2 ¼ 38 units), and the insulin
infusion would be continued for another 2 hours.
The nighttime basal insulin dose would also be 38
units. If this same patient had been eating 100% of
their meals while on the insulin infusion, the 96 units
TDD would be 48 units for basal and 48 units for
prandial insulin requirements. If the total insulin
requirement was not being decreased by 80%, in this
case, the basal insulin would be 24 units once,
another 24 units at bedtime, and the prandial insulin
would be 16 units 3 times per day with meals.
Volume 11, Issue 5, May 2015
INSULIN PUMP THERAPY
With the increased utilization of insulin pump ther-
apy, many institutions are allowing patients to remain
on these devices during their hospitalization,
including during some types of surgery.12 Patients
who use continuous subcutaneous insulin infusion in
the outpatient setting can be considered candidates
for continuation of their insulin pump throughout
their hospitalization, barring no contraindications and
if they have the physical and mental capacity to do so.
The hospital should have a policy and procedures
delineating the inpatient guidelines for continuous
subcutaneous insulin infusion. Throughout the
hospitalization, basal rates, assessments of infusion site,
pump settings, and bolus insulin doses should be
accurately documented in the patient’s medical
record.
CONCLUSION
Data continue to accumulate regarding adverse
effects of poorly controlled diabetes and hyper-
glycemia in the hospitalized patient. Institutions
worldwide are striving to develop safe and effective
ways to manage diabetes and hyperglycemia pro-
actively in the hospital setting. Frequent and
effective glucose monitoring is critical, as is judi-
cious treatment of hyperglycemia while avoiding
hypoglycemia. Overall, glucose targets near 140 mg/dL
are recommended as the most appropriate for the
majority of hospitalized patients, and insulin re-
mains the most appropriate agent for management
of inpatient hyperglycemia. A subcutaneous basal,
bolus, and correction insulin regimen is the
preferred method of achieving and managing
glucose control in nonecritically ill hospitalized
patients.1 Continued use of correction insulin scales
alone as a method of controlling hyperglycemia is
not recommended.
Glycemic management of hospitalized patients
requires ongoing team efforts, education of all
multidisciplinary team members, and careful imple-
mentation of standardized approaches to help ensure
patient safety and promote the best possible outcomes.
www.npjournal.org
Follow-up after hospital discharge requires planning
to provide a smooth transition to outpatient care. A
home health referral should be considered for the
patient, and resources in the community should be
identified. Outpatient diabetes self-management is
critical to minimizing risks of future complications.
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Both authors are affiliated with the Division of Endocrinology at
the Mayo Clinic in Scottsdale, AZ. Patricia A. Mackey, FNP-
BC, BC-ADM, CDE, is an assistant professor of medicine,
Mayo Clinic College of Medicine and can be reached at mackey.
patricia@mayo.edu. Michael D. Whitaker, MD, FRCPC, is
a consultant in endocrinology, assistant professor of Medicine,
Mayo Clinic College of Medicine. In compliance with national
ethical guidelines, the authors report no relationships with business
or industry that would pose a conflict of interest.
1555-4155/15/$ see front matter
© 2015 Elsevier, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.nurpra.2015.02.016
The Journal for Nurse Practitioners - JNP 537