Cover Article

PEER-REVIEWED

Standards of medicai care in diabetes: Focus on updated

recommendations in hospitaiized patients
Mary Choy, PharmD, CGP
Mikel Richman, PharmD candidate

lthough the prevalence of

diabetes mellitus in hospitalized patients remains
unknown, an estimated one-fourth
of inpatients experience hyperglycemia.' Hyperglycemia is linked to
poor health outcomes, and there is
evidence that intensive glucose control in the hospital reduces mortality, need for dialysis, infections, and
length of stay.2 The American Diabetes Association (ADA) publishes
clinical practice guidelines annually,
which offer clinicians, patients, researchers, and payers current, evidence-based recommendations on all
components of diabetes care, general
treatment goals, and tools to evaluate the quality of care. The updated
guidelines focus on changes in the
recommendations for care ofthe hospitalized diabetes patient.
While the management of hyperglycemia in the hospital was traditionally considered secondary in
importance to the condition that
prompted admission, a growing body
of literature supports close glucose
control for potential improvements
in mortality, morbidity, and health
economic outcomes.' The purpose of
this article is to review both the previous and updated recommendations
for inpatient hyperglycemia management, as well as evidence supporting
the guidelines. Additional updated
recommendations will also be discussed.

Abstract
Despite efforts to control biood giucose ieveis in the hospitai, an estimated one-fourth of hospitaiized
patients continue to experience hyperglycemia. Hyperglycemia is linl<ed to poor health outcomes
including an increased risk of mortality, need for dialysis, infections, and length of stay. Tlie American
Diabetes Association (ADA) publishes clinical practice guidelines annually that provide evidence-based
recommendations on ail components of diabetes care, general treatment goals, and tools to evaluate the quality of care. Although previous recommendations discuss intensive biood glucose goals
for hospitaiized patients, updated guidines suggest a more lenient approach to the management
of hyperglycemia. According to the 2009 recommendations, blood glucose levels should be kept as
close to 110 mg/dL as possible and generally less than 140 mg/dL These stringent blood glucose
targets were adopted based on ttie results ofthe study conducted by Van den Berghe et al. In 2010, the
ADA released an updated position statement recommending that blood glucose levels be maintained
between 140 and 180 mg/dL in criticaiiy iil patients based on the findings ofthe Nomnoglycemia in
Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) triai. This article
reviews the evidence supporting the updated guideiines for the management of hyperglycemia
in the hospital setting. Additionai updates to the 2013 recommendations are also discussed.
(Formulary, 2013; 48:189-191.) '

2009 RECOMMENDATIONS

Recommendations from 2009 included intensive blood glucose goals

for hospitalized patients. According to
the recommendations, blood glucose
levels in critically ill patients should be
kept as close to 110 mg/dL as possible
and generally less than 140 mg/dL."
Van den Berghe et al conducted the
study that led to the adoption of stringent blood glucose targets.^ In this trial,
1,200 patients were randomly assigned
to strict normalization of blood glucose
(target between 80 and 110 mg/dL)
with the use of insulin infusion, or to
conventional therapy (insulin administered when blood glucose exceeded 215
mg/dL, with the infusion tapered when
blood glucose fell below 180 mg/dL).

Dr Choy is an assistant professor In the department of pharmacy and health outcomes, Touro College of Pharmacy,
and clinical pharmacist. Metropolitan Hospital, Nev York, N.Y: Ms Richman is a PharmD candidate. Class of 2014, at
Touro College of Pharmacy, Nev York, N.Y.
Disclosure Information: The authors report no financial disclosures as related to products discussed in this article.

Although intensive insulin therapy reduced blood glucose levels, inpatient

mortality was not significantly reduced
for those participants admitted for less
than 3 days. Intensive insulin therapy
significantly reduced morbidity by preventing newly acquired kidney injury,
accelerating weaning from mechanical
ventilation, and accelerating discharge
from the ICU and hospital. There were
more cases of severe hypoglycemia
(blood glucose less than 40 mg/dL)
in the intensive insulin treatment arm.
The results of this landmark trial
should be interpreted with caution,
however, as there are several limitations.
The Van den Berghe trial was a singlecenter study and, as such, the results
should be replicated at other centers
before creating guidelines based on its
findings. The results also demonstrate
an advantage for those treated with
intensive insulin regimens who stayed
in the ICU for more than 3 days; how-

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Table 1
Summary of recommendations in the management of hyperglycemia
NICE-SUGAR Trial
Intensive therapy

Conventional therapy

Patients (n)

3,010

3,012

Total deaths (P=.O2)

27.5%

24.9%

Severe hypoglycemia (P=<.001)

6.8%

0.5%

Updated guidelines
Criticaiiy ill patients

Non-critically ill patients

140-180 mg/dL

Random glucose: <180 mg/dL

Fasting glucose: <140 mg/dL

Blood glucose targets

Abbreviations: NICE-SUGAR, Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation trial
Formu/a/y/Source: Refs 3,6

ever, patients who will have a prolonged

hospital stay cannot be identified on
admission with certainty. Moreover,
there are certain barriers to widespread
adoption of tight glucose control. Tight
glycmie control increases the risk of
severe hypoglycemia and increases the
resources required to achieve normoglycemia. Further multicenter trials are
necessary to confirm the preliminary
findings that intensive glucose control
significantly reduces inpatient morbidity and both morbidity and mortality
in patients with prolonged ICU stays
greater than 3 days' duration.

(NICE-SUGAR) trial.' The NICESUGAR trial was conducted between

December 2004 and November 2008
to test the hypothesis that intensive
glucose control reduces mortality at
90 days. Participants were admitted
to either medical or surgical intensive
care units of 42 hospitals and were
considered eligible if their expected
length of stay was at least 3 days. Of
the 6,104 participants, 3,054 were
randomly assigned to intensive glucose control (target between 81 and
108 mg/dL), and 3,050 were randomly
assigned to conventional glucose control (target of 180 mg/dL or less). The
primary outcome measure was death
2 0 1 0 RECOiVIMENDATIONS
in 2010, the ADA released an updated from any cause within 90 days after
position statement with recommenda- randomization. Secondary outcome
tions for inpatient treatment of hyper- measures were survival time during
glycemia. The guidelines approach the first 90 days, cause-specific death,
management of hyperglycemia in a and durations of mechanical ventilamore lenient manner. According to tion, renal-replacement therapy, and
the recommendations, blood glucose stays in the ICU and hospital.
levels should be maintained between
The results revealed no significant
140 and 180 mg/dL in critically ill differences in the median number of
patients.' These new blood glucose days in the ICU or hospital or the metargets were established based on the dian number of days of mechanical
results of the Normoglycemia in In- ventilation or renal-replacement thertensive Care EvaluationSurvival apy. The results also demonstrated an
Using Glucose Algorithm Regulation increased mortality in the intensive
190

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June 2013 | Vol.48 | Formularyjournal.com

treatment arm. The intensive glucose

control group had an increased absolute risk of death at 90 days of 2.6%
over that of the conventional glucose
control group (27.5% vs 24.9%, respectively). As expected, there were
more cases of severe hypoglycemia in
the intensive treatment group.'
The NICE-SUGAR trial serves as
a landmark in the development of hyperglycemia management protocols.
It had greater statistical power, as well
as a longer follow-up period, than the
previous trial and therefore may reflect
harm not apparent in trials with shorter
follow-up and lower statistical power.
Following the results published by Van
den Berghe et al, intensive glucose control has been widely recommended on
the assumption that treatment aimed
at achieving more stringent blood
glucose targets will benefit patients.
However, as demonstrated by the
findings of the NICE-SUGAR trial,
such a stringent blood glucose target
does not necessarily benefit critically
ill patients and may be harmful. Furthermore, a recent meta-analysis of 26
trials, including the NICE-SUGAR
trial, found a pooled relative risk (RR)
of death with intensive insulin therapy

Cover article

of 0.93 as compared with conventional

therapy. Abouthalf of the trials included reported a pooled RR of 6.0 for hypoglycemia in the intensive treatment
groups.* These findings further support the original results of the NICESUGAR trial.
There is no clear evidence for specific blood glucose levels for non-critically ill patients. Table 1 summarizes
the blood glucose targets for both
critically ill and non-critically ill patients according to the recommendations as well as the contributing trial.
2 0 1 3 ADDITIONAL UPDATES

The ADA also addresses recommendations on the screening of type 1 diabetes in the updated position statement.
Screening for type 1 diabetes has been
revised to include recommendations
concerning the measurement of islet
autoantibodies in relatives of those with
type 1 diabetes. This screening may
allow for earlier identification of the
onset of type 1 diabetes and may reduce
the likelihood of presenting with ketoacidosis upon diagnosis. The guidelines specify that this early screening is
not recommended in low-risk individuals and should be completed within the
setting of a clinical study.
The Standards of Medical Care2013 published additional recommendations for patients with type 1 or type
2 diabetes. Glucose monitoring has
been revised; the new recommendations suggest that patients on multipledose insulin or insulin pump therapy
should self-monitor their blood glucose at least prior to meals and snacks,
occasionally after meals, at bedtime,
prior to exercise, when they suspect
low blood glucose, after treating low
blood glucose, and before critical tasks
such as driving. The guidelines do
not discuss a number of times per day
but encourage individualized testing.
However, according to these recommendations, this will require testing 6
to 8 times daily for many patients.'
Recommendations also include the
administration of hepatitis B vaccine

to unvaccinated adults with diabetes

aged 19 to 59 years. Vaccinations may
be considered in those older than age
60.' Blood pressure goals for patients
with diabetes have been updated as
well. People with diabetes and hypertension should be treated to a blood
pressure goal of less than 140/80 mm
Hg, as compared with previous recommendations of less than 130/80
mm Hg. Lower systolic targets (less
than 130 mm Hg) may be appropriate
for younger individuals, if they can be
achieved without undue burden.'" Finally, dyslipidemia management has
been revised to emphasize the importance of statin therapy in patients with
diabetes and elevated low-density
lipoprotein (LDL) levels. The initiation of statin therapy is no longer indicated by elevated LDL levels above
100 mg/dL alone, but also depends on
patients' risk factors such as history of
heart attack or age over 40 years."
PHARMACIST'S ROLE

It is critical that healthcare professionals appreciate the research behind any

updated recommendations. Pharmacists must be aware of newly published
research supporting or opposing their
hospital's protocols. They should also
recognize the importance of individualized therapy, as the Standards of
Medical Care are simply guidelines to
be followed in most patients and may
not apply to all. Therefore, healthcare
practitioners are encouraged to use
their clinical knowledge and experience to provide the best possible health
outcomes for their patients, in addition to following hospital protocol.
As pharmacists play an active role in
the multidisciplinary healthcare team,
there are growing expectations that
they be prepared to prevent as well
as best manage hyperglycemia in the
hospital. Pharmacists should monitor
blood glucose levels and verify that
hospital protocol is followed correctly.
They may also educate nurses and
other healthcare practitioners regarding the proper use of the hospital's

hyperglycemia management protocol

and how to appropriately adjust the
insulin based on blood glucose levels.
Due to the growing awareness and acceptance of collaborative drug therapy
management, pharmacists will have
an expanding role in patient management in the hospital setting. For this
reason, it is important that pharmacists
utilize their knowledge and skills in
the hospital setting and build a collaborative working relationship with the
other healthcare professionals within
the hospital.
REFERENCES

1. Moghissi ES, Korytkovvski MT, DiNardo

M, et al; American Association of Clinical
Endocrinologists and American Diabetes Association. American Association of Clinical
Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15:353-369.
2. Clement S, Braithwaite SS, Magee MF, et al,
on behalf of the Diabetes in Hospitals Writing Committee. Management of diabetes and
hyperglycemia in hospitals. Diabetes Care.
2004;27:5S3-591.
3. American Diabetes Association. Standards of
medical care in diabetes2013. Position statement. Diabetes Care. 2013;35(Suppl 1):S11-S66.
4. American Diabetes Association. Standards of
medical care in diabetes-2009. Position statement. Diabetes Care. 2009;32(Suppl 1):S13-S61.
5. Van den Berghe G, Wilmer A, Hermans G,
et al. Intensive insulin therapy in the medical
ICU. N Engt J Med. 2006;354:449-461.
6. American Diabetes Association. Standards of
medical care in diabetes-2010. Position statement. Diabetes Care. 2010;33(Suppl 1):S11S61.
7. Finfer S, Chittock DR, Yu-Shuo Su S, et al;
NICE-SUGAR Study Investigators. Intensive
versus conventional glucose control in critically
ill patients. NEnglJMed. 2009;350:1283-1297.
8. Griesdale DE, de Souza RJ, van Dam RM,
et al. Intensive insulin therapy and mortality
among critically ill patients: a meta-analysis
including NICE-SUGAR study data. CMAJ.
2a09;180:821-827.
9. Centers for Disease Control and Prevention.
Use of hepatitis B vaccination for adults with
diabetes mellitus: recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep.
2011;60:1709-1711.
10. McBrien K, Rabi DM, Campbell N, et al. Intensive and standard blood pressure targets in
patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med.
2012;172:1296-1303.
11. Collins R, Armitage J, Parish S, Sleigh P,
Peto R; Heart Protection Study Collaborative
Group. MRC/BHF Heart Protection Study of
cholesterol-lowering with simvastatin in 5,963
people with diabetes: a randomised placebocontrolled trial. Laneet. 2003;361:2005-2016.

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