1. health and fitness
2. disease
3. diabetes

Revisiting Inpatient
Hyperglycemia
New Recommendations,
Evolving Data, and
Practical Implications
for Implementation
Guest Editor: Etie S. Moghissi, MD, FACE
A Supplement to ACP Hospitalist
Release date: December 15, 2009
Expiration date: December 31, 2010
Estimated time to complete activity: 2.0 hours
Sponsored by Postgraduate Institute for Medicine
Supported by an educational grant from
Novo Nordisk Inc.
2
Revisiting Inpatient Hyperglycemia
Revisiting Inpatient Hyperglycemia: New Recommendations, Evolving Data,
and Practical Implications for Implementation
This CME/CE supplement activity is jointly sponsored by Postgraduate Institute for
Medicine, LLC, and Global Directions in Medicine, Inc., and is supported by an educational grant from Novo Nordisk Inc.
Release Date: December 15, 2009
Expiration Date: December 31, 2010
Estimated time to complete activity: 2.0 hours
Content collaborators: Global Directions in Medicine, Inc., and Katherine V. Mann, PharmD
Program Overview
While glucose goals have been established for many years for outpatients with diabetes, only
in the past 6 years have recommendations been established for inpatients with hyperglycemia. The adverse effects associated with hyperglycemia in the hospital setting are well
known and continue to be supported by additional data sets. However, the data on safe and
effective glucose targets in different inpatient settings continue to evolve. The American
Association of Clinical Endocrinologists and the American Diabetes Association have recently revised their consensus statement on the management of inpatient hyperglycemia, recommending more conservative glucose goals. This supplement will review these goals, the evidence supporting these goals, and implementation strategies.
Learning Objectives
Upon completion of the activity, participants should be better able to:
1. Review available data, especially from randomized, controlled trials, on the risks
associated with hyperglycemia in different patient populations and the benefits and
risks of reducing elevated glucose levels.
2. Identify patients at risk for hyperglycemia to appropriately identify and monitor them.
3. Identify patients at risk for hypoglycemia as a result of therapeutic interventions.
4. Describe treatment plans and protocols using intravenous or subcutaneous insulin
to achieve agreed-upon goals with an absolute minimum of severe hypoglycemia.
5. Explain how to assess and implement patient glucose control needs across the continuum of inpatient care and throughout discharge.
Type of Activity
Knowledge
Nursing Continuing Education
Credit Designation
This educational activity for 2.1 contact hours is provided by Postgraduate Institute for
Medicine.
Accreditation Statement
Postgraduate Institute for Medicine is accredited as a provider of continuing nursing
education by the American Nurses Credentialing Center’s Commission on Accreditation.
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There are no fees for participating and receiving CME/CE credit for this activity. During
the period December 15, 2009, through December 31, 2010, participants must 1) read
the learning objectives and faculty disclosures; 2) study the educational activity; and 3)
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on “Find Post-Tests by Course” and search by project ID 6651-ES-14. After you register
and successfully complete the post-test with a score of 70% or better and the evaluation,
your certificate will be made available immediately.
Should you have questions regarding obtaining CME/CE credit, please contact:
Postgraduate Institute for Medicine
303-799-1930, x5286
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Postgraduate Institute for Medicine (PIM) assesses conflict of interest with its instructors, planners, managers, and other individuals who are in a position to control the content of CME activities. All relevant conflicts of interest that are identified are thoroughly
vetted by PIM for fair balance, scientific objectivity of studies utilized in this activity, and
patient care recommendations. PIM is committed to providing its learners with highquality CME activities and related materials that promote improvements or quality in
health care and not a specific proprietary business interest of a commercial interest.
The authors reported the existence or nonexistence of the following relationship(s):
Target Audience
This activity has been designed to meet the educational needs of physicians, registered
nurses, and pharmacists involved in the care of hospitalized patients with diabetes.
Authors
Etie S. Moghissi, MD, FACE (Guest Editor)
Treasurer, American Association of Clinical Endocrinologists
Associate Clinical Professor
Department of Medicine
University of California, Los Angeles
Marina del Rey, California
Name of Faculty
Reported Financial Relationship
Marina Donahue, NP, CDE
Has no financial relationships to disclose
Faramarz Ismail-Beigi, MD, PhD Has no financial relationships to disclose
Mary T. Korytkowski, MD
Has no financial relationships to disclose
Marie E. McDonnell, MD
Fees for non-CME services received directly
from a commercial interest or their agents
(e.g., speakers bureaus): sanofi-aventis
Etie S. Moghissi, MD, FACE
Consulting fees (e.g., advisory boards): Amylin;
Boehringer Ingelheim; Lilly; Merck; Novo Nordisk
Inc. Fees for non-CME services received directly
from a commercial interest or their agents (e.g.,
speakers bureaus): Amylin; Novo Nordisk Inc.
Ownership interest (stocks, stock options or other
ownership interest excluding diversified mutual
funds): Amylin; Novo Nordisk Inc.
Marina Donahue, NP, CDE
Boston Medical Center
Boston, Massachusetts
Faramarz Ismail-Beigi, MD, PhD
Professor of Medicine and Physiology and Biophysics
Case Western Reserve University
Cleveland, Ohio
Mary T. Korytkowski, MD
Professor of Medicine
Department of Medicine
Division of Endocrinology and Metabolism
University of Pittsburgh
Pittsburgh, Pennsylvania
Marie E. McDonnell, MD
Assistant Professor of Medicine
Director, Inpatient Diabetes Program
Boston Medical Center
Boston, Massachusetts
Physician Continuing Medical Education
Accreditation Statement
This activity has been planned and implemented in accordance with the Essential Areas
and policies of the Accreditation Council for Continuing Medical Education (ACCME)
through the joint sponsorship of Postgraduate Institute for Medicine (PIM) and Global
Directions in Medicine. PIM is accredited by the ACCME to provide continuing medical education for physicians.
Credit Designation
Postgraduate Institute for Medicine designates this educational activity for a maximum of
2.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate
with the extent of their participation in the activity.
Pharmacist Continuing Education
Accreditation Statement
Postgraduate Institute for Medicine is accredited by the Accreditation Council for
Pharmacy Education as a provider of continuing pharmacy education.
Credit Designation
Postgraduate Institute for Medicine designates this continuing education activity for 2.1
contact hours (0.21 CEUs) of the Accreditation Council for Pharmacy Education.
(Universal Activity Number: 809-999-09-140-H01-P)
The following PIM planners and managers, Linda Graham, RN, BSN, BA, Jan Hixon,
RN, BSN, MA, Trace Hutchison, PharmD, Julia Kirkwood, RN, BSN, Samantha
Mattiucci, PharmD, and Jan Schultz, RN, MSN, CCMEP, hereby state that they or their
spouse/life partner do not have any financial relationships or relationships to products or
devices with any commercial interest related to the content of this activity of any amount
during the past 12 months.
Katherine V. Mann, PharmD, and the content collaborators at Global Directions in
Medicine, Inc., have no financial relationships to disclose.
On behalf of Global Directions in Medicine, Katherine V. Mann, PharmD, performed a
clinical review, identification of supporting references, and data check of content, and
Lynda Seminara performed editorial review of content for grammar, syntax, and spelling,
as well as stylized content in accordance with guidelines set forth by the American
Medical Association's Manual of Style. All authors received payment from Global
Directions in Medicine via an educational grant from Novo Nordisk Inc.
Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses
of agents that are not indicated by the Food and Drug Administration. Postgraduate
Institute for Medicine (PIM), Global Directions in Medicine, Inc., and Novo Nordisk
Inc. do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily
represent the views of PIM, Global Directions in Medicine, Inc., and Novo Nordisk Inc.
Please refer to the official prescribing information for each product for discussion of
approved indications, contraindications, and warnings.
Disclaimer
The information presented in this activity is not meant to serve as a guideline for patient
management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of
their patients’ conditions and possible contraindications on dangers in use, review of any
applicable manufacturers’ product information, and comparison with recommendations of
other authorities. The views expressed in the supplement are those of the authors, not ACP,
and do not represent official College policy or positions unless so stated.
Cover photograph: Getty Images.
Revisiting Inpatient Hyperglycemia
3
Table of Contents
Chapter 1: The Importance of Managing Hyperglycemia in Hospitalized Patients and the Evolution of Treatment Guidelines
Etie S. Moghissi, MD, FACE
3
Chapter 2: Reexamining the Evidence: In Which Hyperglycemic Inpatients Does Improving Glycemic Control Improve Outcomes?
Faramarz Ismail-Beigi, MD, PhD
7
Chapter 3: Treatment Options for Safely Achieving Glycemic Targets in the Hospital
Mary Korytkowski, MD
Chapter 4: Transitioning Patients Along the Continuum of Care—Intravenous to Subcutaneous Insulin,
Inpatient to Outpatient Settings: Practical Considerations
Marie E. McDonnell, MD, and Marina Donahue, MS, NP, CDE
15
24
Chapter 1
The Importance of Managing
Hyperglycemia in Hospitalized
Patients and the Evolution of
Treatment Guidelines
By Etie S. Moghissi, MD, FACE
The economic burden of diabetes in the United States in
2007 was estimated to be $174 billion. Hospitalization was
the major component, making up 50% of the total.1 The
prevalence of diabetes among hospitalized adults is conservatively estimated to range from 12% to 25%, depending on the
thoroughness used to identify patients. Data from 2005 show
that almost 6 million hospitalizations had diabetes listed as a
diagnosis.2 Nationally, one third of adults with diabetes are
unaware of their condition,3 which may not be recognized
until a patient is hospitalized for some complication related to
the diabetes.
Hyperglycemia in the hospital setting, whether or not the
patient is critically ill, is associated with poorer outcomes.
These include increased morbidity and mortality among
patients with a previous diagnosis of diabetes, as well as those
with newly recognized glucose abnormalities.4 The risks may
be greater in patients with no diagnosis of diabetes than those
with known diabetes. Inpatient hyperglycemia is also associated with longer hospital stays.5,6
Hyperglycemia in the hospital can present in different
patient populations. These include patients with known diabetes who are admitted for another medical reason, those with
previously undiagnosed diabetes who are identified and diagnosed when evaluated during hospitalization, and otherwise
healthy individuals in whom the hyperglycemia may be
induced by trauma or critical illness, known as stress hyperglycemia.7 In a study conducted in a community teaching hospital with a 38% prevalence of inpatient hyperglycemia, one
third of these patients were identified as having newly discovered hyperglycemia.8
A decade ago, the significance of acute hyperglycemia in
the inpatient setting was not fully appreciated; therefore,
managing hyperglycemia was not a priority, and sliding-scale
insulin was a common mode of therapy. To complicate matters, there were no published glycemic targets or treatment
guidelines for inpatients. The early studies in patients admitted with acute myocardial infarction, or for cardiac or other
surgery,9–11 brought attention to the importance of inpatient
hyperglycemia and created a need to examine the evidence
and develop practice guidelines. On the basis of impressive
findings from a European study12 of critically ill surgical
patients treated with intravenous insulin to a treatment goal of
80 to 110 mg/dL (4.4 to 6.1 mmol/L), which showed improvement in mortality and measures of serious morbidity, treatment
4
Revisiting Inpatient Hyperglycemia
Table 1. Successful strategies for
improving inpatient glycemic control
Diabetes champions
Administrative support
Multidisciplinary steering committee to drive the
development of initiatives:
Medical staff, nursing and case management, pharmacy,
nutrition services, dietary services, laboratory, quality
improvement, information systems, administration
Assessment of current processes, quality of care, and
barriers to practice change
Development and implementation of interventions, including:
Standardized order sets, protocols, policies, and
algorithms with associated educational programs
Metrics for evaluation
goals for critically ill patients were developed in 2004. In that
year, the American Diabetes Association (ADA) published a
technical review.7 At the same time, the American Association
of Clinical Endocrinologists (AACE) convened a consensus
conference that brought multiple organizations together to
examine the evidence and publish the first inpatient glycemic
targets.13 These recommendations set relatively stringent glucose targets of less than 110 mg/dL (6.1 mmol/L) for critically
ill patients; preprandial targets of 110 mg/dL and postprandial
targets of 180 mg/dL (10.0 mmol/L) were set for non–critically
ill patients. It was acknowledged that the available data were
limited and that further research for these patients would be
needed.
In 2005, the ADA included inpatient glycemic control
recommendations in the annual standards of care.14 As a
result, many hospitals initiated efforts to follow the new recommendations. Multiple barriers were identified, however,
and the implementation of good glycemic control became a
challenge. In 2006, the AACE and ADA came together for a
“call to action” and recommended strategies to overcome the
barriers (Table 1).15
Recently, more experience and data have emerged from
clinical trials of many more patients from many different
countries. Although hyperglycemia is associated with adverse
patient outcomes, interventions to normalize glycemia have
yielded inconsistent results. These conflicting findings have
called into question the benefit of tight control16–18 and have
highlighted the risk for severe hypoglycemia resulting from
such efforts.19–21
Growing confusion and frustration among health care professionals in many institutions prompted an urgent need for
uniform guidance from the professional societies to bring clarity. Responding to this need, the AACE and ADA came together once again in early 2009 to reexamine the accumulated
evidence and translate the implications into clinical practice.
The effort was aimed at recommending reasonable, achievable, and safe glycemic targets; identifying pitfalls affecting
patient safety; and suggesting strategies for safe and effective
glycemic control from admission to discharge. In the absence
of strong evidence demonstrating decreased mortality resulting
from intensive blood glucose management, and given serious
concerns about safety and increased risk for severe hypoglycemia associated with this approach, the glycemia targets
were revised in the 2009 AACE/ADA consensus statement
(Table 2).4 This statement recommends a blood glucose target
of 140 to 180 mg/dL (7.8 to 10.0 mmol/L) for most critically
ill patients.
Greater benefit may be realized at the lower end of this
range. Although strong evidence is lacking, somewhat lower
glucose targets may be appropriate in selected patients, such
as the surgical population in units that have shown low rates
of hypoglycemia. However, targets below 110 mg/dL (6.1
mmol/L) are no longer recommended.
The 2008 scientific statement on hyperglycemia and
acute coronary syndrome published by the American Heart
Association16 recommends that in the coronary care unit,
maintaining plasma glucose levels of 90 to 140 mg/dL (5.0 to
7.8 mmol/L) with intravenous insulin is a reasonable goal if
severe hypoglycemia is avoided. For cardiac patients hospitalized in a non–intensive care unit setting, maintaining plasma
glucose levels below 180 mg/dL (10.0 mmol/L) with subcutaneous insulin regimens is also recommended.
Among non–critically ill patients admitted to general surgical and medical services, the presence of hyperglycemia in
patients with and without the diagnosis of diabetes has been
associated with prolonged hospital stay, infection, disability
after hospital discharge, and death.22–25 These observational
studies suggest that hyperglycemia is associated with poor
clinical outcomes; however, no randomized, controlled studies
have examined the benefit of glycemic control on clinical outcomes in non–critically ill patients. Therefore, the recommended glycemia targets for this patient population are based
Table 2. Current glycemic targets in
hospitalized patients
All critically ill patients in intensive care unit settings
Blood glucose level 140–180 mg/dL (7.78–10.0 mmol/L)
Intravenous insulin preferred
Non–critically ill patients
Premeal: <140 mg/dL (7.78 mmol/L)
Random: <180 mg/dL (10.0 mmol/L)
Scheduled subcutaneous dosing preferred
Hypoglycemia
Reassess the regimen if blood glucose level is
<100 mg/dL (5.56 mmol/L)
Modify the regimen if blood glucose level is <70 mg/dL
(3.89 mmol/L)
Sliding-scale insulin
Discouraged
Revisiting Inpatient Hyperglycemia
on clinical experience, judgment, and consensus. The recent
AACE/ADA consensus panel recommends a premeal glucose
level of less than 140 mg/dL (7.8 mmol/L) and maximum glucose level of less than 180 mg/dL (10.0 mmol/L) in non–
critically ill patients. For patients in that category who have
diabetes and have been treated successfully to lower targets in
the outpatient setting, lower targets may also be acceptable.
The use of regularly scheduled subcutaneous insulin injections is the most common and most physiologic method for
controlling hyperglycemia in this patient population.4
These recent recommended targets per the 2009
AACE/ADA consensus statement reflect a balanced approach
for treating hyperglycemia while avoiding hypoglycemia.4 The
evidence base used to establish the recommendations is
reviewed in detail in the chapter by Ismail-Beigi (page 7).
As for what methods can be used to manage hyperglycemia
in the hospital, the use of intravenous insulin infusions is recommended to control hyperglycemia in the intensive care setting.5
Among patients who are not critically ill, regularly scheduled
subcutaneous insulin injections are the most common method.5
However, the number of insulin products has increased dramatically in the past 10 years, often leading to complex and varied
treatment regimens that may confuse physicians and nurses in
the hospital, particularly those not familiar with scheduled
basal–bolus insulin therapy. In addition, many insulin products
have similar indications and pharmacokinetics. In this supplement, Korytkowski reviews treatment options for achieving
glycemic targets in the hospital (page 15).
Poor communication of medication instructions at the
time of hospital discharge has been linked to medication
errors and adverse drug events.26,27 This is particularly true for
insulin regimens, which may differ from the doses used at
home. Most insulin regimens are complex, consisting of at
least 2 types of insulin; doses are supposed to be modified on
the basis of results of home glucose readings. The day of hospital discharge is not always conducive to retaining complicated verbal communication about medication use.28 The usual
generic patient-discharge forms typically are not sufficient for
providing detailed diabetes instructions. A recent retrospective
study by Lauster and colleagues examined instructions provided to patients who were discharged from general medicine
units before and after the availability of a standardized insulinspecific discharge form.29 Their findings demonstrated greater
clarity and more consistent instructions on appropriate timing
and dosing. This topic is discussed in more depth in
McDonnell and Donahue’s chapter on transitioning patients
along the continuum of care (page 24).
A growing national movement views the management of
hyperglycemia in hospitals as a quality-of-care measure. For
example, as part of the Surgical Care Improvement Project,
a blood glucose level of 200 mg/dL (11.1 mmol/L) or less at
6 a.m. the morning after cardiac surgery is mandated to
help minimize the risk for postoperative infections.30 The
Joint Commission has published certification and recognition recommendations for disease-specific care, including
diabetes and inpatient diabetes. Efforts to manage inpatient
5
hyperglycemia have been associated with economic benefits
to hospitals in several studies.31–34
The National Quality Forum has identified “serious
reportable events,” also called “never events,” defined as
“errors in medical care that are clearly identifiable, preventable, and serious in their consequences for patients, and that
indicate a real problem in the safety and credibility of a health
care facility.”35 Third-party payors, including the Centers for
Medicare & Medicaid Services, have begun to withhold payments for care related to these types of events. CMS categorizes death or serious disability associated with hyperglycemia
or hypoglycemia as “never events.”
In summary, hospitalized patients represent a dynamic
patient population. It should be emphasized that clinical
judgment and ongoing assessment of patients, including
their severity of illness, nutritional status, and concomitant
use of other medications (such as steroids and changes in
blood glucose level), must be incorporated into the day-today decisions regarding insulin dosing. It is also important to
consider the resources that are available, in particular those
in the institution, to treat hyperglycemia safely. The management of inpatient hyperglycemia will probably continue to
evolve with more experience, more research, and greater
understanding of the pathophysiology of hyperglycemia in
different patient populations.
References
1. American Diabetes Association. Economic costs of diabetes in
the U.S. in 2007. Diabetes Care. 2008;31:596-615. [PMID:
18308683]
2. Centers for Disease Control and Prevention. Number (in thousands) of hospital discharges with diabetes as first-listed diagnosis, United States, 1980–2005. 2005. Accessed at
www.cdc.gov/diabetes/Statistics/dmfirst/fig1.htm on 5
November 2009.
3. Centers for Disease Control and Prevention. National Diabetes
Fact Sheet, 2007. Accessed at http://cdc.gov/diabetes/pubs/
pdf/ndfs_2007.pdf on 5 November 2009.
4. Moghissi ES, Korytkowski MT, DiNardo M; American
Association of Clinical Endocrinologists. American Association
of Clinical Endocrinologists and American Diabetes Association
consensus statement on inpatient glycemic control. Endocr
Pract. 2009;15:353-69. [PMID: 19454396]
5. Estrada CA, Young JA, Nifong LW, Chitwood WR Jr. Outcomes
and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting. Ann
Thorac Surg. 2003;75:1392-9. [PMID: 12735552]
6. Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia
as a prognostic indicator in trauma. J Trauma. 2003;55:33-8.
[PMID: 12855878]
7. Clement S, Braithwaite SS, Magee MF; American Diabetes
Association Diabetes in Hospitals Writing Committee.
Management of diabetes and hyperglycemia in hospitals.
Diabetes Care. 2004;27:553-91. [PMID: 14747243]
8. Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM,
Kitabchi AE. Hyperglycemia: an independent marker of in-hospital
mortality in patients with undiagnosed diabetes. J Clin
Endocrinol Metab. 2002;87:978-82. [PMID: 11889147]
6
Revisiting Inpatient Hyperglycemia
9. Malmberg K. Prospective randomised study of intensive insulin
treatment on long term survival after acute myocardial infarction
in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus,
Insulin Glucose Infusion in Acute Myocardial Infarction) Study
Group. BMJ. 1997;314:1512-5. [PMID: 9169397]
10. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous
intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical
procedures. Ann Thorac Surg. 1999;67:352-60; discussion
360-2. [PMID: 10197653]
11. Krinsley JS. Glycemic control, diabetic status, and mortality in a
heterogeneous population of critically ill patients before and
during the era of intensive glycemic management: six and onehalf years experience at a university-affiliated community hospital. Semin Thorac Cardiovasc Surg. 2006;18:317-25. [PMID:
17395028]
12. van den Berghe G, Wouters P, Weekers F, Verwaest C,
Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the
critically ill patients. N Engl J Med. 2001;345:1359-67. [PMID:
11794168]
13. Garber AJ, Moghissi ES, Bransome ED Jr; American College of
Endocrinology Task Force on Inpatient Diabetes Metabolic
Control. American College of Endocrinology position statement
on inpatient diabetes and metabolic control. Endocr Pract.
2004;10:77-82. [PMID: 15251626]
14. American Diabetes Association. Standards of medical care in
diabetes. Diabetes Care. 2005;28 Suppl 1:S4-S36. [PMID:
15618112]
15. ACE/ADA Task Force on Inpatient Diabetes. American College
of Endocrinology and American Diabetes Association consensus statement on inpatient diabetes and glycemic control.
Endocr Pract. 2006;12:458-68. [PMID: 16983798]
16. van den Berghe G, Wilmer A, Hermans G, Meersseman W,
Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449-61. [PMID: 16452557]
17. Brunkhorst FM, Engel C, Bloos F, et al; German Competence
Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med.
2008;358:125-39. [PMID: 18184958]
18. Finfer S, Chittock DR, Su SY, et al; NICE-SUGAR Study
Investigators. Intensive versus conventional glucose control in
critically ill patients. N Engl J Med. 2009;360:1283-97. [PMID:
19318384]
19. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight
glucose control in critically ill adults: a meta-analysis. JAMA.
2008;300:933-44. [PMID: 18728267]
20. Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook
DJ, Malhotra A, et al. Intensive insulin therapy and mortality
among critically ill patients: a meta-analysis including NICESUGAR study data. CMAJ. 2009;180:821-7. [PMID:
19318387]
21. Krinsley JS, Grover A. Severe hypoglycemia in critically ill
patients: risk factors and outcomes. Crit Care Med.
2007;35:2262-7. [PMID: 17717490]
22. Pomposelli JJ, Baxter JK 3rd, Babineau TJ, Pomfret EA, Driscoll
DF, Forse RA, et al. Early postoperative glucose control predict
nosocomial infection rate in patients. JPEN J Parenter Enteral
Nutr. 1998;22:77-81. [PMID: 9527963]
23. McAlister FA, Majumdar SR, Blitz S, Rowe BH, Romney J,
Marrie TJ. The relation between hyperglycemia and outcomes in
2,471 patients admitted to the hospital with communityacquired pneumonia. Diabetes Care. 2005;28:810-5. [PMID:
15793178]
24. Baker EH, Janaway CH, Philips BJ, Brennan AL, Baines DL,
Wood DM, et al. Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations
of chronic obstructive pulmonary disease. Thorax.
2006;61:284-9. [PMID: 16449265]
25. Noordzij PG, Boersma E, Schreiner F, Kertai MD, Feringa HH,
Dunkelgrun M, et al. Increased preoperative glucose levels are
associated with perioperative mortality in patients undergoing
noncardiac, nonvascular surgery. Eur J Endocrinol.
2007;156:137-42. [PMID: 17218737]
26. Kripalani S, Jackson AT, Schnipper JL, Coleman EA. Promoting
effective transitions of care at hospital discharge: a review of
key issues for hospitalists. J Hosp Med. 2007;2:314-23.
[PMID: 17935242]
27. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The
incidence and severity of adverse events affecting patients after
discharge from the hospital. Ann Intern Med. 2003;138:161-7.
[PMID: 12558354]
28. Donihi AC, Yang E, Mark SM, Sirio CA, Weber RJ. Scheduling
of pharmacist-provided medication education for hospitalized
patients. Hosp Pharm. 2008;43:121-126.
29. Lauster CD, Gibson JM, DiNella JV, DiNardo M, Korytkowski
MT, Donihi AC. Implementation of standardized instructions for
insulin at hospital discharge [Letter]. J Hosp Med. 2009;4:E412. [PMID: 19827044]
30. National Quality Measures. Surgical care improvement project:
percent of cardiac surgery patients with controlled 6 A.M. postoperative blood glucose. Accessed at www.qualitymeasures
.ahrq.gov/summary/summary.aspx?ss=1&doc_id=13233 on 5
November 2009.
31. Newton CA, Young S. Financial implications of glycemic control: results of an inpatient diabetes management program.
Endocr Pract. 2006;12 Suppl 3:43-8. [PMID: 16905516]
32. van den Berghe G, Wouters PJ, Kesteloot K, Hilleman DE.
Analysis of healthcare resource utilization with intensive insulin
therapy in critically ill patients. Crit Care Med. 2006;34:612-6.
[PMID: 16521256]
33. Olson L, Muchmore J, Lawrence CB. The benefits of inpatient
diabetes care: improving quality of care and the bottom line.
Endocr Pract. 2006;12 Suppl 3:35-42. [PMID: 16905515]
34. Krinsley JS, Jones RL. Cost analysis of intensive glycemic control in critically ill adult patients. Chest. 2006;129:644-50.
[PMID: 16537863]
35. Centers for Medicare & Medicaid Services Office of Public
Affairs. Eliminating serious, preventable, and costly medical
errors; never events [press release]. 18 May 2006.
Revisiting Inpatient Hyperglycemia
7
Chapter 2
Reexamining the Evidence: In
Which Hyperglycemic Inpatients
Does Improving Glycemic
Control Improve Outcomes?
By Faramarz Ismail-Beigi, MD, PhD
Results of observational and epidemiologic studies have
demonstrated that hyperglycemia is associated with higher rates
of death and adverse outcomes in a variety of medical and surgical conditions, independent of its underlying cause.1–11
Hyperglycemia can occur in patients with known or undiagnosed
diabetes or can result from acute illness or stressful conditions.12,13 This last, also known as “stress-induced” hyperglycemia, is not related to diabetes, but has been reported as the
most common cause of hyperglycemia in critically ill
patients.5,8,14,15 Such hyperglycemia is a reversible hypermetabolic state with several alterations in glucose metabolism,
including whole-body insulin resistance, increased gluconeogenesis, enhanced non–insulin-mediated glucose disposal, elevated
blood lactate levels, and changes in counterregulatory
hormones.13,16,17 This stress-induced hyperglycemia is associated
with a high risk for complications and death.5,8,14,18–20
Because hyperglycemia, especially in critically ill patients, is
strongly associated with poor clinical outcomes, studies have
examined whether decreasing the elevated glucose levels (with
insulin) toward normal physiologic levels improves patient outcomes. The results of several studies testing this hypothesis are
described in the following sections, with an emphasis on recent
randomized, controlled trials. The reader is referred to previous
summary statements for historical context of this evolving
field21,22 and to the recent American Association of Clinical
Endocrinologists/American Diabetes Association consensus statement on inpatient glycemic control.23,24 As will also be discussed
later, evidence from randomized, controlled trials on the effect of
glucose control in hyperglycemic inpatients (non–intensive care
unit [ICU] settings) is not available, a major deficiency in the
current evidence base.
Intensive glucose control
in surgical, medical, and
mixed ICUs
Several early interventional, nonrandomized studies documented that hyperglycemia occurring in the first 2 days after
cardiothoracic surgical procedures was associated with higher
rates of wound infection (approximately 2-fold greater).25,26 The
Portland Diabetic Project, a prospective nonrandomized study,
examined the effect of intravenous insulin therapy to control
glycemia in post–cardiac surgery patients. This intervention
resulted in a significant reduction in the rates of sternal infection
and cardiac-related mortality.2,7 Control of glycemia in a mixed
medical/surgical ICU setting was associated with reduced mortality in another nonrandomized study.27
Table 1 summarizes the results of several randomized, controlled trials enrolling more than 200 critically ill patients in
medical, surgical, or mixed ICUs.23 A landmark randomized,
controlled study conducted in a single surgical ICU assessed the
effect of intensive glycemic control with intravenous insulin
infusion to target arterial glucose levels of 80 to 110 mg/dL (4.4
to 6.1 mmol/L). Among the 1548 patients from this single surgical ICU, the mortality rate was 8.0% for the conventional group
and 4.6% for the intensive treatment group (only among patients
who stayed in the ICU for ≥5 days).5 A significant number of
patients had undergone a surgical cardiac revascularization procedure. Rates of sepsis, renal failure, blood transfusion, and critical illness–related polyneuropathy were reduced. Severe hypoglycemia (blood glucose level ≤40 mg/dL [2.2 mmol/L])
occurred in 7.0% of the intensive group and 1.1% of the standard treatment group.5
In contrast to the preceding findings, a similar protocol in
1200 participants, used by the same investigative group in the
medical ICU of the same institution, did not significantly
reduce overall mortality; however, the mortality rate was significantly lower (approximately 18%) for patients who stayed
in the ICU for 3 or more days.20 The number of patients who
experienced 1 or more hypoglycemic events (blood glucose
level ≤40 mg/dL [2.2 mmol/L]) was increased 6-fold in the
intensive group (18.7% vs. 3.1%); mean blood glucose levels
during hypoglycemia were 31 mg/dL (SD, 8) (1.7 mmol/L
[SD, 0.5]) in the intensive group and 32 mg/dL (SD, 8) (1.8
mmol/L [SD, 0.4]) in the conventional treatment group. Of
note, the authors identified hypoglycemia as an independent
risk factor for death.20
Revisiting Inpatient Hyperglycemia
8
Table 1. Summary data: selected randomized clinical trials of intensive insulin
therapy in critically ill patients (>200 randomized patients)
Trial
Patients,
n
VISEP14
Setting
Blood
glucose
achieved,
mg/dL
(mmol/L) *
C
I
Primary
outcome
End point
rate, %
C
I
ARR,
%†
RRR,
%†
Odds
ratio†
(95% CI)
537‡
ICU
151
(8.4)
112
(6.2)
28-d
mortality
26.0
24.7
1.3
5.0
0.89§||
(0.58–1.38)
Glucontrol29 1078
ICU
144
(8)
118
(6.6)
ICU
mortality
15.3
17.2
–1.9
–12
1.10||
(0.84–1.44)
De La
Rosa30¶
504
ICU
148
(8.2)
117
(6.5)
28-d
mortality
32.4
36.6
–4.2||
–13||
NR
NICESUGAR34
6104
ICU
145
(8.0)
115
(6.4)
3-mo
mortality
24.9
27.5
–2.6
–10.6
1.14**
(1.02–1.28)
DIGAMI-143
620
CCU
(AMI)
211
(11.7)
173
(9.6)
1-y
mortality
26.1
18.6
7.5
29**
NR
DIGAMI-244 1253
CCU
(AMI)
180
(10)
164
(9.1)
2-y
mortality
–||
–||
NR
240
CCU AMI
(GIK)
162
(9)
149
(8.3)
6-mo
mortality
6.1
7.9
1.8||
–30||
NR
van den
Berghe5
1548
SICU
153
(8.5)
103
(5.7)
ICU
mortality
8.0
4.6
3.4
42
0.58**
(0.38–0.78)
van den
Berghe20
1200
MICU
153
(8.5)
111
(6.2)
Hospital
mortality
40.0
37.3
2.7
7.0
0.94||
(0.84–1.06)
Intraoperative38
399
Operating
room
157
(8.7)
114
(6.3)
Composite††
46
44
2
4.3
1.0||
(0.8–1.2)
HI-545
Grp. 3: Grp. 1:
17.9
23.4;
grp. 2:
21.2
AMI = acute myocardial infarction; ARR = absolute risk reduction; C = Conventional; DIGAMI = Diabetes and Insulin-Glucose Infusion in Acute
Myocardial Infarction; GIK = glucose–insulin–potassium; HI-5 = Hyperglycemia: Intensive Insulin Infusion in Infarction; I = Intensive; ICU =
intensive care unit (mixed); MICU = medical intensive care unit(s); NICE-SUGAR = Normoglycemia in Intensive Care Evaluation–Survival Using
Glucose Algorithm Regulation; NR = not reported; RRR = relative risk reduction; SICU = surgical intensive care unit; VISEP = Efficacy of
Volume Substitution and Insulin Therapy in Severe Sepsis.
* Mean morning blood glucose concentrations, except for Glucontrol, which reported mean overall blood glucose concentrations.
†
Intensive group vs. conventional group.
‡
Sepsis patients only.
§
Brunkhorst F. Personal communication.
||
Not significant (P>0.05).
¶
Presented only as an abstract.
** P<0.05.
†† Composite
of death, sternal infection, prolonged ventilation, cardiac arrhythmias, stroke, and renal failure at 30 days.
Revisiting Inpatient Hyperglycemia
The multicenter randomized Glucontrol study (n = 1078)
showed no decrease in mortality and a higher incidence of
hypoglycemia (8.7% in the tight glycemic control group vs.
2.7% in the conventional control group); concerns for safety
and other protocol-related issues prompted early termination
of this trial.28,29 The authors also noted that mortality was 2.4fold higher for patients who had experienced 1 or more severe
hypoglycemic events.29 The Efficacy of Volume Substitution
and Insulin Therapy in Severe Sepsis (VISEP) study reported
no decrease in mortality (targeting the blood glucose range of
80 to 110 mg/dL [4.4 to 6.1 mmol/L] compared with a control
group that achieved glucose levels of around 150 mg/dL [8.3
mmol/L]) and higher rates of severe hypoglycemia in patients
with severe sepsis who received intensive insulin therapy than
in those who received conventional insulin therapy (17% vs.
4.1%; P<0.001), as well as an increased rate of serious adverse
events (10.9% vs. 5.2%, respectively).14 Hypoglycemia (blood
glucose level ≤40 mg/dL [2.2 mmol/L]) was an independent
risk factor for death (relative risk, 2.2 at 28 days [95% CI, 1.6
to 3.0]) (Brunkhorst F. Personal communication). Similarly, a
study on the effect of intensive glycemic control in a mixed
medical/surgical ICU in Colombia resulted in no decrease in
morbidity or mortality, but the rate of severe hypoglycemia
increased 5-fold.30
A meta-analysis of 29 randomized, controlled trials examining the effect of intensive glycemic control among 8432
patients in surgical, medical, and mixed medical/surgical
ICUs was reported recently.31 Glycemic targets ranged from
72 to 126 mg/dL (4.0 to 7.0 mmol/L) (usually 80 to 110
mg/dL [4.4 to 6.1 mmol/L]) and 150 to 220 mg/dL (8.3 to
12.2 mmol/L) (usually 180 to 200 mg/dL [10.0 to 11.1
mmol/L]), with achieved mean glucose levels of approximately
115 mg/dL (6.4 mmol/L) in the intensive group and approximately 160 mg/dL (8.9 mmol/L) in the usual care group. The
analysis also included studies with less intensive targets. With
the exception of 2 studies,5,32 hospital mortality did not differ
between the intensive and control groups (21.6% vs. 23.3%,
respectively) and did not differ when stratified by intensive,
less intensive, and control (usual care) glucose goals. Intensive
glycemic control was associated with a decrease in septicemia
(mostly in the surgical ICU) but did not reduce the risk for
dialysis. Of note, intensive glucose control was associated
with an aggregate 5.13-fold increase in the rate of hypoglycemia (blood glucose level ≤40 mg/dL [2.2 mmol/L];
13.7% vs. 2.5%) that was seen regardless of the type of
ICU.31 This meta-analysis concluded that tight glycemic
control in critically ill adults does not reduce hospital mortality but increases the risk for hypoglycemia. An accompanying editorial emphasized the need to develop standardized
methods of both measuring and defining glucose control in
critically ill patient populations.33
Results of the multicenter, multinational
Normoglycemia in Intensive Care Evaluation–Survival
Using Glucose Algorithm Regulation (NICE-SUGAR) trial
were published recently.34 A total of 6104 adults in several
medical and surgical ICUs were randomly assigned to
receive intensive (blood glucose level, 81 to 108 mg/dL [4.5
9
to 6.0 mmol/L]) or less intensive (blood glucose level ≤180
mg/dL [10.0 mmol/L]) treatment (Table 1). Achieved
glycemic levels were 115 mg/dL (6.4 mmol/L) for the
intensive group and 145 mg/dL (8.0 mmol/L) for the less
intensive group. Mortality at 90 days (the primary outcome)
was significantly higher in the intensive group (78 more
deaths occurred in the intensive group [27.5% vs. 24.9%];
P=0.02). Most deaths were from cardiovascular causes,
which were more common in the intensive group (76 more
deaths [41.6% vs. 35.8%]; P=0.02). Mortality at 30 days was
also higher among patients treated intensively, but the difference was not significant. No difference was noted in
length of ICU or hospital stay. Compared with standard
glycemic therapy, intensive treatment was associated with
more frequent episodes of severe hypoglycemia (0.5% vs.
6.8%; P<0.001). Editorialists have commented that nonadherence to protocols may have contributed to these findings, thus raising the issue of whether protocols that work
in smaller study samples can be generalizable to and implemented in average-size hospitals.
A more recent meta-analysis of insulin infusion protocols in critical illness included the NICE-SUGAR results.35
Data derived from 13,567 participants from various randomized trials showed no decrease in overall mortality for
patients who received intensive glycemic control. However,
the authors concluded that intensive glycemic control may
have a favorable effect in surgical ICU patients (mostly
those who have just undergone coronary artery bypass grafting) (relative risk, 0.63 [CI, 0.44 to 0.91]). Overall, intensive glycemic control was associated with a 6-fold higher
rate of severe hypoglycemia.
Table 2 summarizes the rates of severe hypoglycemia in
some of the recent glycemia trials. Most of these studies
defined severe hypoglycemia as a blood glucose level less
than 40 mg/dL (2.2 mmol/L), a level significantly lower
than the standard definition of less than 70 mg/dL (3.9
mmol/L) in non–critically ill persons.36 It is reasonable to
believe that values of 40 mg/dL (2.2 mmol/L) or less might
be dangerously low, given that many critically ill patients in
ICUs are on ventilators, are obtunded, and may not be able
to mount all the counterregulatory mechanisms against
hypoglycemia. The 3- to 6-fold higher rate of hypoglycemia
observed with intensive insulin therapy14,20,31,34 indicates
that the higher rates of serious adverse events and mortality
in the hypoglycemia subgroup might in part offset the
potential benefits gained by strict glycemic control in the
much larger group that did not have hypoglycemic
events.14,20 However, arguing against this premise is the
finding that, in the studies detailed earlier, severe hypoglycemic events were infrequently directly linked to mortality; this suggests that hypoglycemia may be a marker of serious underlying disease rather than a cause of death. In
addition to the increased risk for death associated with
severe hypoglycemia, such episodes are associated with
much discomfort, stress for the patient and family members, increased cost, and, potentially, dementia in older
patients with type 2 diabetes.
10
Revisiting Inpatient Hyperglycemia
Table 2. Rates of severe hypoglycemia in selected trials
Trial
van den Berghe5
van den Berghe20
HI-545
VISEP14
De La Rosa30
Glucontrol29
NICE-SUGAR34
Intensive
group, %*
Less intensive
group, %
Intensive/
less intensive
5.0
18.7
10.3
17.0
8.5
8.7
6.8
0.8
3.1
1.7
4.1
1.7
2.7
0.5
6.3
6.0
6.1
4.1
5.0
3.2
13.6
HI-5 = Hyperglycemia: Intensive Insulin Infusion in Infarction; NICE-SUGAR = Normoglycemia in Intensive Care Evaluation–Survival Using
Glucose Algorithm Regulation; VISEP = Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis.
* Values denote the percentage of patients experiencing ≥1 severe hypoglycemic events (blood glucose level ≤40 mg/dL [2.2 mmol/L]).
Studies on glycemic
management during
surgical procedures
In a randomized, double-blind, placebo-controlled study
of 82 adults, intraoperative glucose–insulin–potassium infusion during coronary bypass surgery did not reduce myocardial
damage or improve intraoperative cardiac performance in
patients without contractile dysfunction.37 In another study,
399 patients undergoing cardiac surgical procedures were
assigned to the insulin infusion group or the conventional
group;38 after surgery, both groups underwent insulin infusion.
Results showed no significant reduction in the primary outcome (composite end point of death, sternal infection, prolonged ventilation, arrhythmias, stroke, and renal failure
within 30 days after surgery) or the secondary outcome
(length of stay in the ICU and hospital). High-dose insulin
(5 mU/kg body weight per minute) and dextrose infusion in
patients who had elective coronary bypass surgery resulted in
significantly lower levels of interleukin-6, interleukin-8, and
tumor necrosis factor-α in the early postoperative period.39
However, the study did not examine the potential effect of
these reductions on clinical outcomes.
Glycemic control in
patients with acute
myocardial infarction
An association between hyperglycemia and adverse outcomes after acute myocardial infarction (AMI) has been documented.18,40 For example, a study of 16,971 patients with
AMI41 showed a direct correlation between hyperglycemia and
in-hospital mortality. Nevertheless, it is not known whether
hyperglycemia is mediator of post-AMI complications or
merely a marker of the patient’s underlying health status.
The American Heart Association recently published a scientific statement on this topic.42
In the Diabetes and Insulin-Glucose Infusion in Acute
Myocardial Infarction (DIGAMI) study, 620 diabetic
patients with AMI were assigned to receive intensive or
conventional blood glucose management, both in the hospital and after discharge.43 Mortality rates were 19% for the
intensive group and 26% for the conventional group. The
multicenter DIGAMI-2 study assessed whether the
observed risk reduction was attributable to the inpatient or
outpatient components of the therapeutic intervention.44 A
total of 1253 diabetic patients with AMI were randomly
assigned to 1 of 3 treatment strategies: insulin infusion followed by aggressive outpatient therapy, insulin infusion
alone, or conventional diabetes care. At 2 years, mortality
rates did not differ among the groups. In the Hyperglycemia
Intensive Insulin Infusion in Infarction (HI-5) study, 240
diabetic participants with AMI were randomly assigned to
receive insulin infusion for at least 24 hours (blood glucose
goal <180 mg/dL [10.0 mmol/L]) or conventional diabetes
management.45 Mortality rates were not different in the
hospital, at 3 months, or at 6 months. Other studies of glucose–insulin–potassium infusions have also had conflicting
results.46 The largest study, Clinical Trial of Reviparin and
Metabolic Modulation–Estudios Cardiológicos Latin
America (CREATE-ECLA), randomly assigned 20,201
patients in 470 centers worldwide; it found no mortality
benefit with glucose–insulin–potassium treatment.47
Spontaneous, noniatrogenic hypoglycemia is associated
with poor outcomes.48–50 A J-shaped distribution between
average glucose and mortality was observed, with hypoglycemia being associated with adverse outcomes. Similarly,
2 earlier investigations49,50 suggested that hypoglycemia (unrelated to diabetes) during AMI portended a poorer prognosis.
Further, in a study of 7924 patients with AMI at 40 U.S. hospitals, hypoglycemia was a predictor of higher mortality among
patients who were not treated with insulin.48
Revisiting Inpatient Hyperglycemia
Glycemic control in
neurosurgical ICUs and
after burns or trauma
Several retrospective studies have examined the relationship between glycemia and clinical outcomes in patients with
extensive burns, body trauma, or traumatic brain injury and
those who have just had surgery for cerebral aneurysms.51–61
Pasternak and colleagues61 reviewed the records of 1000
patients who had undergone aneurysm clipping for subarachnoid hemorrhage. Three months after surgery, patients whose
blood glucose level was 129 mg/dL (7.1 mmol/L) or greater
were more likely to have impaired cognition, and those with a
level greater than 152 mg/dL (8.4 mmol/L) had more deficits
in gross neurologic function according to the National
Institutes of Health Stroke Scale. Sung and colleagues62
reported that nondiabetic patients with severe blunt injury
and hyperglycemia on admission had higher rates of infection,
longer hospital stays, and a 2.2-fold higher rate of mortality
after adjustment for age and Injury Severity Score. Although
mortality benefits have not been observed in similar studies,63–65 decreased rates of infection have been associated
with lower blood glucose levels.65
The effect of tight glycemic control on outcomes was
determined in a randomized, controlled trial of 97 patients
with severe traumatic brain injury.66 The rate of hypoglycemia
was approximately 2-fold higher for the intensive group.
Although the ICU stay was shorter for the intensive group
(7.3 vs. 10.0 days), no differences were found in the rate of
infection during ICU stay, the mortality rate at 6 months, or
the neurologic outcomes measured by using the Glasgow
Outcome Scale. In a randomized, controlled trial of 78
patients who had just had surgery for subarachnoid hemorrhage, the rate of infection was lower for the intensive
group.67 However, the incidence of postoperative vasospasm
and the overall mortality rate at 6 months did not change significantly. The power of these smaller studies may not have
been sufficient to demonstrate benefit.
Data from patients who
underwent transplantation
To my knowledge, there are no reports of randomized,
controlled trials in transplant populations. Fuji and
colleagues68 examined the potential effects of hyperglycemia
during neutropenic periods in 112 patients who underwent
myeloablative allogeneic hematopoietic stem-cell transplantation. The incidence of fever and infections during neutropenia
did not vary with glycemia. However, glycemia was associated
with a risk for organ failure, grade II to IV acute graft-versushost disease, and nonrelapse mortality. A report on 382
patients not treated with glucocorticoids during neutropenia
showed that each 10-mg/dL (0.56-mmol/L) increase in blood
glucose was associated with a 1.15-fold increase in the odds
ratio for bacteremia. Derr69 and Hammer70 and their colleagues analyzed blood glucose levels in a retrospective cohort
11
study of 1175 adults who had undergone allogeneic
hematopoietic cell transplantation. Hyperglycemia and hypoglycemia correlated with nonrelapse mortality within 200 days
of the transplant procedure, and glycemic variability was
strongly associated with mortality.
Glucose control in
hospitalized medical and
surgical patients
in non-ICU settings
As mentioned earlier, no randomized, controlled trials
have been conducted among these patients, a major shortcoming. In the studies discussed in this section, it is not known
whether the elevated blood glucose is a marker of underlying
disease severity or an independent risk factor for disease progression. Many observational studies indicate a strong association between hyperglycemia and poor clinical outcomes in
various hospital (non-ICU) settings.12,18,71–78 The presence of
hyperglycemia in patients with and those without diabetes has
been associated with prolonged hospital stay, infection, disability after hospital discharge, and death.12,71,72,78,79 Among
1886 patients admitted to a community hospital, the mortality
rate on the general floors was significantly higher for patients
with newly diagnosed hyperglycemia than for those with
known diabetes.71 In a multicenter cohort study of 2471
patients, those with admission glucose levels greater than
198 mg/dL (11.0 mmol/L) had a greater risk for death and
complications than those with glucose levels less than
198 mg/dL (11.0 mmol/L).78 Among 348 patients with chronic obstructive pulmonary disease and respiratory tract infection, the relative risk for death was 2.10 for those with a blood
glucose level of 126 to 160 mg/dL (7.0 to 8.9 mmol/L) and
3.42 for those with a level greater than 160 mg/dL (8.9
mmol/L) compared with patients whose level was less than
108 mg/dL (6.0 mmol/L).79 Furthermore, each 18 mg/dL
(1.0 mmol/L) increase in blood glucose was associated with a
15% increase in the risk for death or a length of stay exceeding 9 days. Similarly, general surgery patients with hyperglycemia also have a higher risk for adverse outcomes.72,80
Commentary
Available evidence suggests that very tight glycemic control (target blood glucose of 80 to 110 mg/dL [4.4 to 6.1
mmol/L]), as reported in the first Leuven trial5 in surgical
ICU patients, may have benefits, including decreased mortality, reduction of wound infections, and reduction in septicemia
in post–cardiac surgery patients.5 Most subsequent studies in
surgical, medical, and mixed ICUs have not replicated those
findings, especially the reduction in mortality.14,20,34,81 The
reasons for this discrepancy are not entirely clear. The originally reported positive results might have been attributable to
patient selection (mostly patients who had undergone coronary artery bypass grafting) or to chance alone. Alternatively,
12
Revisiting Inpatient Hyperglycemia
the results may reflect the patients’ high degree of caloric support in the form of glucose infusion and parenteral nutrition,
which would be expected to cause hyperglycemia. As noted
earlier, attempts to tightly control glycemia can lead to high
rates of hypoglycemia, a complication that has been identified
as an independent risk factor for death.
However, the conclusion from the present analysis should
not be that judicious control of glycemia is not warranted in
critically ill patients or in hospital settings in general. Reasons
for judicious control of glycemia in hospital settings include
the following. First, many observational studies in a variety of
settings clearly show that hyperglycemia is associated with
poor outcomes. Second, whereas most experts would agree
that the reported rates of hypoglycemia for intensively managed patients are unacceptably high, hypoglycemic events
could probably be minimized with improvement in, standardization of, and careful implementation of protocols. Additional
tools that help translate protocols into practice are urgently
needed. More important, relaxation of the target range of 80
to 110 mg/dL (4.4 to 6.1 mmol/L) for intensive control of
glycemia to a higher range would be expected to result in
lower rates of hypoglycemia. Third, the achieved difference
in blood glucose levels between the intensive and standard
glycemia treatment groups (approximately 45 mg/dL
[2.5 mmol/L] in most studies) may not have been large
enough to allow investigators to discern a statistically significant difference between the groups. The determination of
an appropriate and effective target range is an important
topic for future research.
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27. Krinsley JS. Glycemic control, diabetic status, and mortality in a
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the era of intensive glycemic management: six and one-half years
experience at a university-affiliated community hospital. Semin
Thorac Cardiovasc Surg. 2006;18:317-25. [PMID: 17395028]
28. Devos P, Preiser JC, Mélot C; Glucontrol Steering Committee.
Impact of tight glucose control by intensive insulin therapy on
ICU mortality and the rate of hypoglycaemia: final results of the
Glucontrol study. Intensive Care Med. 2007;33:S189.
29. Preiser JC, Devos P, Ruiz-Santana S, Mélot C, Annane D,
Groeneveld J, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy
in adult intensive care units: the Glucontrol study. Intensive
Care Med. 2009;35:1738-48. [PMID: 19636533]
30. De La Rosa GC, Donado JH, Restrepo AH; Grupo de
Investigacion en Cuidado intensivo: GICI-HPTU. Strict glycaemic control in patients hospitalised in a mixed medical and
surgical intensive care unit: a randomised clinical trial. Crit
Care. 2008;12:R120. [PMID: 18799004]
31. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight
glucose control in critically ill adults: a meta-analysis. JAMA.
2008;300:933-44. [PMID: 18728267]
32. Wang LC, Lei S, Wu YC, Wu JN, Wang LF, Guan TR, et al.
[Intensive insulin therapy in critically ill patients]. Zhongguo Wei
Zhong Bing Ji Jiu Yi Xue. 2006;18:748-50. [PMID: 17166358]
33. Finfer S, Delaney A. Tight glycemic control in critically ill adults
[Editorial]. JAMA. 2008;300:963-5. [PMID: 18728273]
34. NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med.
2009;360:1283-97. [PMID: 19318384]
35. Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ,
Malhotra A, et al. Intensive insulin therapy and mortality among
critically ill patients: a meta-analysis including NICE-SUGAR study
data. CMAJ. 2009;180:821-7. [PMID: 19318387]
36. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes.
Diabetes Care. 2003;26:1902-12. [PMID: 12766131]
37. Shim YH, Kweon TD, Lee JH, Nam SB, Kwak YL. Intravenous
glucose-insulin-potassium during off-pump coronary artery
bypass surgery does not reduce myocardial injury. Acta
Anaesthesiol Scand. 2006;50:954-61. [PMID: 16923090]
38. Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, O’Brien
PC, et al. Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized
trial. Ann Intern Med. 2007;146:233-43. [PMID: 17310047]
13
39. Albacker T, Carvalho G, Schricker T, Lachapelle K. High-dose
insulin therapy attenuates systemic inflammatory response in
coronary artery bypass grafting patients. Ann Thorac Surg.
2008;86:20-7. [PMID: 18573392]
40. Kosiborod M, Rathore SS, Inzucchi SE, Masoudi FA, Wang Y,
Havranek EP, et al. Admission glucose and mortality in elderly
patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes.
Circulation. 2005;111:3078-86. [PMID: 15939812]
41. Kosiborod M, Inzucchi SE, Krumholz HM, Xiao L, Jones PG,
Fiske S, et al. Glucometrics in patients hospitalized with acute
myocardial infarction: defining the optimal outcomes-based
measure of risk. Circulation. 2008;117:1018-27. [PMID:
18268145]
42. Deedwania P, Kosiborod M, Barrett E; American Heart
Association Diabetes Committee of the Council on Nutrition,
Physical Activity, and Metabolism. Hyperglycemia and acute
coronary syndrome: a scientific statement from the American
Heart Association Diabetes Committee of the Council on
Nutrition, Physical Activity, and Metabolism. Circulation.
2008;117:1610-9. [PMID: 18299505]
43. Malmberg K, Rydén L, Efendic S, Herlitz J, Nicol P,
Waldenström A, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic
patients with acute myocardial infarction (DIGAMI study):
effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:5765. [PMID: 7797776]
44. Malmberg K, Ryden L, Wedel H; DIGAMI 2 Investigators.
Intense metabolic control by means of insulin in patients with
diabetes mellitus and acute myocardial infarction (DIGAMI 2):
effects on mortality and morbidity. Eur Heart J. 2005;26:65061. [PMID: 15728645]
45. Cheung NW, Wong VW, McLean M. The Hyperglycemia:
Intensive Insulin Infusion in Infarction (HI-5) study: a randomized
controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care. 2006;29:765-70. [PMID: 16567812]
46. Fath-Ordoubadi F, Beatt KJ. Glucose-insulin-potassium in acute
myocardial infarction [Letter]. Lancet. 1999;353:1968. [PMID:
10371590]
47. CREATE-ECLA Trial Group Investigators. Effect of glucoseinsulin-potassium infusion on mortality in patients with acute STsegment elevation myocardial infarction: the CREATE-ECLA
randomized controlled trial. JAMA. 2005;293:437-46. [PMID:
15671428]
48. Kosiborod M, Inzucchi SE, Goyal A, Krumholz HM, Masoudi FA,
Xiao L, et al. Relationship between spontaneous and iatrogenic
hypoglycemia and mortality in patients hospitalized with acute
myocardial infarction. JAMA. 2009;301:1556-64. [PMID:
19366775]
49. Pinto DS, Skolnick AH, Kirtane AJ, et al; TIMI Study Group. Ushaped relationship of blood glucose with adverse outcomes
among patients with ST-segment elevation myocardial infarction
[Letter]. J Am Coll Cardiol. 2005;46:178-80. [PMID:
15992655]
50. Svensson AM, McGuire DK, Abrahamsson P, Dellborg M.
Association between hyper- and hypoglycaemia and 2 year allcause mortality risk in diabetic patients with acute coronary
events. Eur Heart J. 2005;26:1255-61. [PMID: 15821004]
51. Bochicchio GV, Joshi M, Bochicchio KM, Pyle A, Johnson SB,
Meyer W, et al. Early hyperglycemic control is important in critically injured trauma patients. J Trauma. 2007;63:1353-8; discussion 1358-9. [PMID: 18212660]
14
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52. Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia
as a prognostic indicator in trauma. J Trauma. 2003;55:33-8.
[PMID: 12855878]
53. Gale SC, Sicoutris C, Reilly PM, Schwab CW, Gracias VH.
Poor glycemic control is associated with increased mortality in
critically ill trauma patients. Am Surg. 2007;73:454-60. [PMID:
17520998]
54. Jeremitsky E, Omert LA, Dunham CM, Wilberger J, Rodriguez
A. The impact of hyperglycemia on patients with severe brain
injury. J Trauma. 2005;58:47-50. [PMID: 15674149]
55. Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC.
Relationship of early hyperglycemia to mortality in trauma
patients. J Trauma. 2004;56:1058-62. [PMID: 15179246]
56. Wahl WL, Taddonio M, Maggio PM, Arbabi S, Hemmila MR.
Mean glucose values predict trauma patient mortality. J Trauma.
2008;65:42-7; discussion 47-8. [PMID: 18580507]
57. Duane TM, Ivatury RR, Dechert T, Brown H, Wolfe LG, Malhotra
AK, et al. Blood glucose levels at 24 hours after trauma fails to
predict outcomes. J Trauma. 2008;64:1184-7. [PMID:
18469639]
58. Cochran A, Davis L, Morris SE, Saffle JR. Safety and efficacy of
an intensive insulin protocol in a burn-trauma intensive care unit.
J Burn Care Res. 2008;29:187-91. [PMID: 18182920]
59. Vogelzang M, van der Horst IC, Nijsten MW. Hyperglycaemic
index as a tool to assess glucose control: a retrospective study.
Crit Care. 2004;8:R122-7. [PMID: 15153239]
60. Mowery NT, Gunter OL, Guillamondegui O, Dossett LA, Dortch
MJ, Morris JA Jr, et al. Stress insulin resistance is a marker for
mortality in traumatic brain injury. J Trauma. 2009;66:145-51;
discussion 151-3. [PMID: 19131817]
61. Pasternak JJ, McGregor DG, Schroeder DR; IHAST
Investigators. Hyperglycemia in patients undergoing cerebral
aneurysm surgery: its association with long-term gross neurologic and neuropsychological function. Mayo Clin Proc.
2008;83:406-17. [PMID: 18380986]
62. Sung J, Bochicchio GV, Joshi M, Bochicchio K, Tracy K, Scalea
TM. Admission hyperglycemia is predictive of outcome in critically ill trauma patients. J Trauma. 2005;59:80-3. [PMID:
16096543]
63. Collier B, Diaz J Jr, Forbes R, Morris J Jr, May A, Guy J, et al.
The impact of a normoglycemic management protocol on clinical outcomes in the trauma intensive care unit. JPEN J Parenter
Enteral Nutr. 2005;29:353-8; discussion 359. [PMID:
16107598]
64. Shin S, Britt RC, Reed SF, Collins J, Weireter LJ, Britt LD. Early
glucose normalization does not improve outcome in the critically ill trauma population. Am Surg. 2007;73:769-72; discussion
772. [PMID: 17879682]
65. Hemmila MR, Taddonio MA, Arbabi S, Maggio PM, Wahl WL.
Intensive insulin therapy is associated with reduced infectious
complications in burn patients. Surgery. 2008;144:629-35; discussion 635-7. [PMID: 18847648]
66. Bilotta F, Caramia R, Cernak I, Paoloni FP, Doronzio A, Cuzzone
V, et al. Intensive insulin therapy after severe traumatic brain
injury: a randomized clinical trial. Neurocrit Care. 2008;9:15966. [PMID: 18373223]
67. Bilotta F, Spinelli A, Giovannini F, Doronzio A, Delfini R, Rosa G.
The effect of intensive insulin therapy on infection rate, vasospasm,
neurologic outcome, and mortality in neurointensive care unit after
intracranial aneurysm clipping in patients with acute subarachnoid
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
hemorrhage: a randomized prospective pilot trial. J Neurosurg
Anesthesiol. 2007;19:156-60. [PMID: 17592345]
Fuji S, Kim SW, Mori S, Fukuda T, Kamiya S, Yamasaki S, et al.
Hyperglycemia during the neutropenic period is associated with
a poor outcome in patients undergoing myeloablative allogeneic
hematopoietic stem cell transplantation. Transplantation.
2007;84:814-20. [PMID: 17984832]
Derr RL, Hsiao VC, Saudek CD. Antecedent hyperglycemia is
associated with an increased risk of neutropenic infections during bone marrow transplantation. Diabetes Care.
2008;31:1972-7. [PMID: 18650374]
Hammer MJ, Casper C, Gooley TA, O’Donnell PV, Boeckh M,
Hirsch IB. The contribution of malglycemia to mortality among
allogeneic hematopoietic cell transplant recipients. Biol Blood
Marrow Transplant. 2009;15:344-51. [PMID: 19203725]
Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM,
Kitabchi AE. Hyperglycemia: an independent marker of in-hospital
mortality in patients with undiagnosed diabetes. J Clin
Endocrinol Metab. 2002;87:978-82. [PMID: 11889147]
Pomposelli JJ, Baxter JK 3rd, Babineau TJ, Pomfret EA, Driscoll
DF, Forse RA, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. JPEN J
Parenter Enteral Nutr. 1998;22:77-81. [PMID: 9527963]
Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC.
Stress hyperglycemia and prognosis of stroke in nondiabetic
and diabetic patients: a systematic overview. Stroke.
2001;32:2426-32. [PMID: 11588337]
Bruno A, Gregori D, Caropreso A, Lazzarato F, Petrinco M,
Pagano E. Normal glucose values are associated with a lower
risk of mortality in hospitalized patients. Diabetes Care.
2008;31:2209-10. [PMID: 18716050]
Norhammar AM, Rydén L, Malmberg K. Admission plasma glucose. Independent risk factor for long-term prognosis after
myocardial infarction even in nondiabetic patients. Diabetes
Care. 1999;22:1827-31. [PMID: 10546015]
Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and
mortality in critically ill patients. JAMA. 2003;290:2041-7.
[PMID: 14559958]
Montori VM, Bistrian BR, McMahon MM. Hyperglycemia in
acutely ill patients. JAMA. 2002;288:2167-9. [PMID:
12413377]
McAlister FA, Majumdar SR, Blitz S, Rowe BH, Romney J,
Marrie TJ. The relation between hyperglycemia and outcomes in
2,471 patients admitted to the hospital with communityacquired pneumonia. Diabetes Care. 2005;28:810-5. [PMID:
15793178]
Baker EH, Janaway CH, Philips BJ, Brennan AL, Baines DL,
Wood DM, et al. Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations
of chronic obstructive pulmonary disease. Thorax.
2006;61:284-9. [PMID: 16449265]
Noordzij PG, Boersma E, Schreiner F, Kertai MD, Feringa HH,
Dunkelgrun M, et al. Increased preoperative glucose levels are
associated with perioperative mortality in patients undergoing
noncardiac, nonvascular surgery. Eur J Endocrinol.
2007;156:137-42. [PMID: 17218737]
Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight
glucose control in critically ill adults: a meta-analysis. JAMA.
2008;300:933-44. [PMID: 18728267]
Revisiting Inpatient Hyperglycemia
15
Chapter 3
Treatment Options for Safely
Achieving Glycemic Targets
in the Hospital
By Mary Korytkowski, MD
The recent American Association of Clinical Endocrinologists/American Diabetes Association (AACE/ADA)
consensus panel recommends glycemic targets of 140 to
180 mg/dL (7.8 to 10.0 mmol/L) for most hospitalized
patients, with and without critical illness.1 Among critically
ill patients, initiation of insulin therapy is recommended at
blood glucose thresholds of no more than 180 mg/dL
(10 mmol/L), and preferably when levels exceed 140 mg/dL
(7.8 mmol/L). For patients who are not in critical care units,
the recommended fasting and preprandial glycemic targets
are a blood glucose level less than 140 mg/dL (7.8 mmol/L)
and a random glucose level less than 180 mg/dL (10
mmol/L). These targets approximate the mean glycemic values required to maintain hemoglobin A1c levels of 7% to 8%
in the outpatient setting.2 Patients who are clinically stable
and who experienced tight glycemic control in the outpatient
setting may be candidates for more intensive management in
the hospital if this can be achieved safely. For certain groups
of critically ill patients (for example, those who have just had
coronary artery bypass surgery or a vascular procedure),
modification of glycemic targets to 110 to 140 mg/dL (6.1 to
7.8 mmol/L) may be appropriate.3,4
These glycemic targets were selected to guide a rational
approach to inpatient glycemic management that both avoids
uncontrolled hyperglycemia and minimizes the risk for hypoglycemia.1 Presented herein is a review of management strategies that are effective in achieving the recommended glycemic
targets in both critically and non–critically ill patients. I also
discuss oral and the newer noninsulin injectable agents.
Intravenous insulin
infusion protocols
Validated intravenous (IV) insulin infusion protocols that
are efficacious in achieving and maintaining desired glycemic
targets with a low risk for hypoglycemia are preferred for critically ill patients.1 IV insulin decreases blood glucose levels in
a reasonable time period (6 to 10 hours), permits rapid titration of dose for anticipated (for example, initiation or discontinuation of vasopressors) or unanticipated (for example, acute
deteriorations in clinical status) changes in a patient’s clinical
status and minimizes glycemic excursions more effectively
than does subcutaneous (SC) insulin.5 Situations associated
with changes in insulin requirements include changes in
nutrition, dialysis, medications (for example, octreotide and
glucocorticoids), and the administration of medications (for
example, antibiotics) in dextrose-containing solutions.
Although both regular and rapid-acting insulin analogues
are approved for IV use, there is no advantage to using the
more expensive analogues for IV infusion therapy because the
biological half-life of IV regular insulin is short. There may be
a rationale for use of the rapid-acting analogues as part of SC
insulin regimens. Thus, it is recommended that human regular insulin be used for all IV insulin infusions. It is recommended that institutions use a single insulin concentration in
these infusions to avoid any confusion about dose or potential
errors related to having more than one concentration.6 At my
institution, the standard formula is 1 unit of regular insulin
per milliliter of solute.
There are more than 20 published IV insulin infusion
protocols in the literature.1,6–12 Although most protocols produce favorable results in maintaining blood glucose levels
within a specified range (with a variable incidence of hypoglycemia), modification of the updated glycemic targets is recommended. Hence, ongoing analysis of glycemic control data
is essential.1,13,14
The development and implementation of any protocol
depend greatly on its acceptance by hospital personnel across
a variety of disciplines. Many protocols can appear complicated at first glance.6,15–17 For optimal execution, critical care
nurses should have the primary responsibility for initiating and
titrating insulin infusions according to a defined algorithm.
For this reason, their input into and acceptance of a protocol
is essential to success 18,19
Nurses can ensure that a protocol achieves the desired
levels of glycemic control if they are given clear instructions
for insulin initiation and adjustments. Support from medical
and nursing directors of a critical care unit, together with educational programs and small group meetings with nurses during each shift, promotes successful implementation of an IV
insulin infusion protocol.6 Timely feedback of aggregated performance data (scorecards) will further create a culture of
improvement and lead to sustainability of gains.
16
Revisiting Inpatient Hyperglycemia
Obstacles to
implementation of an IV
insulin infusion protocol
Identified obstacles to the success of an IV insulin infusion protocol include fear of hypoglycemia and related adverse
events, difficulty in abandoning practices that may have had
variable success, increases in nurse workload, and the requirement for increases in the numbers of glucose meters and
materials needed to achieve glycemic targets.6 The relaxation
of glycemic targets from 80 to 110 mg/dL (4.4 to 6.1 mmol/L)
to 140 to 180 mg/dL (7.8 to 10.0 mmol/L) in critical care
areas may lead to improved blood glucose control because the
higher target reduces the risk for hypoglycemia.20 Nurse workload has been addressed in some institutions by training
patient care technicians to obtain samples for blood glucose
measurements and to enter data into bedside or electronic
flow sheets.
Elements of a safe IV
insulin infusion protocol
Protocols with demonstrated safety and efficacy consider
certain essential elements, including current and previous
blood glucose levels and the current rate of insulin infusion.
Adjustments are made according to the rate of change or stability from the previous reading. This helps minimize the risk
for hypoglycemia or undesired reductions in blood glucose levels. Several hospitals have created Web sites and computer
algorithms that guide these changes in infusion rates and have
reported improved glycemic outcomes compared with paperbased protocols.11,21,22
Another element of a safe and effective IV insulin infusion protocol is the frequency of blood glucose monitoring.23
With initiation of any protocol in a critically ill patient, hourly
monitoring with adjustments in insulin infusion rates is essential. Once the blood glucose levels and infusion rate have
been stable for 2 to 4 hours, the frequency of blood glucose
monitoring can be decreased to every 2 hours. With prolonged
stability, many protocols allow monitoring every 4 hours if the
patient’s clinical status does not change. Any change in nutrition, glucocorticoid therapy, or vasopressor therapy requires a
return to more frequent glucose monitoring.
The sampling site and device used for obtaining point-ofcare blood glucose measurements have been identified as a
source of potential error and risk in hospitalized patients.24 In
the initial Leuven study, all blood glucose samples were
obtained from an arterial line and measured in the critical
care laboratory.3 Subsequent studies have reported variability
in sites for blood sampling and monitoring devices.20,23 This
can result in lower levels of accuracy and reproducibility of
blood glucose measurements, with associated errors in adjustments of insulin infusions. There is a need to standardize not
only the insulin infusion protocols used but also the source of
sampling for blood glucose measurements and the device used
to obtain the results. Many hospitals have interfaced blood
glucose measurements into a centralized repository for data
aggregation and analysis. Rates of hypoglycemia and hyperglycemia, as well as blood glucose averages by nursing unit,
can thus be easily determined; these data allow greater oversight of glucose control efforts.
The route of nutrition administration (that is, IV, parenteral, enteral) has also been associated with variability in
the risk for hypoglycemia with IV insulin infusions in critically
ill patients. It is recommended that all patients receive some
form of caloric supplementation, such as continuous dextrose
infusions or enteral or parenteral nutrition, to avoid catabolic
stress and minimize the risk for hypoglycemia.25
Transition from IV to
SC insulin
IV insulin infusions usually are continued for the duration
of mechanical ventilation, volume resuscitation, and vasopressor and nutrition support. As patients improve and are transferred from a critical care unit, they are also transitioned from
IV to SC insulin to avoid deteriorations in glycemic control.26,27 Although some institutions have had success with IV
insulin infusion protocols outside the critical care units10,28,
all patients treated with IV insulin will eventually require transition to SC insulin before discharge. Deployment of IV
insulin infusion protocols outside of intensive care units must
be done with extreme caution given increased nurse-to-patient
ratios, decreased resources for blood glucose monitoring, and
the associated increased risk for hypoglycemia. Upon conversion, the dose of SC insulin is determined from the recent
history of IV insulin requirements immediately prior at the
time of transition, with consideration of nutritional status, use
of concurrent medications (such as corticosteroid therapy),
and history of diabetes. In a study of patients in a surgical
intensive care unit, an SC insulin dose calculated as 80%
(compared with 40% or 60%) of the insulin requirement in
the preceding 24 hours was more effective at maintaining
glycemic targets of 80 to 150 mg/dL (4.4 to 8.3 mmol/L) in
the next 24 hours.26,29 A study of patients in a medical intensive care unit compared different strategies of transitioning
from IV to SC insulin.27 Patients who received scheduled
basal and short- or rapid-acting insulin calculated as approximately 66% of the previous 24-hour insulin requirement had
more blood glucose values in the goal range of 80 to 180
mg/dL (4.4 to 10.0 mmol/L) than those who received slidingscale insulin alone or in combination with basal insulin.27 The
frequency of moderate or severe hypoglycemia with the more
intensive strategies did not differ in either of these studies.
What is important at the time of transition is that the
SC insulin be administered 1 to 2 hours before discontinuation of the insulin infusion. This allows sufficient time for
the SC insulin to be absorbed and active, reducing the risk
for clinically significant hyperglycemia during the transition
period.5 For practical considerations and case studies on
this topic, see the chapter in this supplement by
McDonnell and Donahue (page 24).
Revisiting Inpatient Hyperglycemia
SC insulin therapy
Scheduled SC insulin that includes an intermediate or
long-acting insulin preparation (basal insulin) in combination
with short- or rapid-acting insulin (bolus) is the preferred
method of glycemic management for most patients with a history of diabetes or new-onset hyperglycemia in non–critical
care hospital settings (Table 1). A correction insulin scale,
rather than a reactive sliding-scale insulin, can be added to
scheduled insulin therapy to allow for the administration of
supplemental doses of short- or rapid-acting insulin when
blood glucose level exceeds the glycemic target.30–33
In general, any patient who uses scheduled insulin therapy at home will require scheduled insulin therapy in the hospital, although dose adjustments may be required.
Unfortunately, sliding-scale insulin, which is reactive and not
a proactive physiologic approach, remains the treatment of
choice for clinicians at many institutions. The practice of discontinuing oral diabetes medications or insulin therapy and
starting sliding-scale insulin as the only glycemic management
strategy results in undesirable levels of both hypoglycemia and
hyperglycemia and places the patient at increased risk at transitions if medication reconciliation is not done appropriately.34,35 Sliding-scale insulin has been abandoned altogether by
some institutions,36 where use of correction insulin in conjunction with scheduled SC insulin to regulate blood glucose
excursions that are outside the desired range is
deployed.32,33,37–39
In some situations, the use of correction insulin alone
may be acceptable. Patients with no history of diabetes, those
with previously well-controlled type 2 diabetes who are admitted with elevated blood glucose levels, or those who begin a
therapy known to be associated with hyperglycemia in many
patients (corticosteroids, enteral or parenteral nutrition) can
have blood glucose monitoring performed with insulin administration in accordance with a correction scale to determine
the need for scheduled insulin therapy.38,40,41 Although a small
percentage of patients who become hyperglycemic with these
therapies can achieve glycemic control with correction insulin
alone, most will require scheduled insulin therapy with longor intermediate-acting insulin in combination with short- or
rapid-acting analogues.33,38,39 For patients who do not become
hyperglycemic, blood glucose monitoring can be discontinued
after 36 to 48 hours. The challenge remains: Clinical inertia
regarding glucose control is widespread, and patients who
begin receiving sliding-scale insulin often continue to do so
throughout the admission.
Appropriate and safe use of scheduled insulin therapy
is complicated by various factors: prescribers’ lack of familiarity with the different insulin preparations, the need for
contingencies in insulin dosing for variability in nutritional
status (for example, nothing by mouth around the time of
procedures), and concerns about hypoglycemia.30–32
Implementation of protocols outlining the major components of insulin therapy has reduced the dependence on
sliding-scale insulin and increased the percentage of orders
for physiologic insulin therapy.32
The safety of scheduled SC basal–bolus insulin therapy in
the hospital has been demonstrated in 2 studies of inpatients
with type 2 diabetes.33,37 In 1 study, glycemic control was
achieved more effectively with basal–bolus insulin than with
sliding-scale insulin in insulin-naive patients with type 2 diabetes. A blood glucose target of less than 140 mg/dL (7.8
mmol/L) was achieved in two thirds of patients receiving
basal–bolus therapy with insulin analogues compared with less
than 40% of patients in the sliding-scale insulin group. Despite
increasing insulin doses, 14% of patients treated with slidingscale insulin remained with blood glucose levels greater than
240 mg/dL (13.3 mmol/L).33 In the other study, 2 insulin regimens (detemir and aspart vs. neutral protamine Hagedorn and
regular insulin) resulted in similar levels of glycemic control
(mean, 160 mg/dL [SD, 38] and 158 mg/dL [SD, 51], respectively [8.9 mmol/L (SD, 21) and 8.8 mmol/L (SD, 2.8)]) and a
similar frequency of hypoglycemia, defined as blood glucose
level less than 60 mg/dL (3.3 mmol/L) (32.8% vs. 25.4%).
With these studies used as a guide, a suggested method
for initiating scheduled inpatient insulin therapy is based on
body weight (Table 2). In the above-mentioned studies, a
starting dose of 0.4 U/kg per day was used for blood glucose
values of 140 to 200 mg/dL (7.8 to 11.1 mmol/L) and 0.5
U/kg per day for blood glucose values greater than 200 mg/dL
(11.1 mmol/L). Note that most patients in these trials were
obese and therefore were likely to be more insulin resistant.
When body weight is used to calculate total daily insulin
doses, the multiplier ranges from 0.2 to 0.5 U/kg per day,
depending on the assessed level of insulin sensitivity (Table 2).42
Table 1. Pharmacokinetics of insulin preparations
Type of insulin
Rapid-acting analogues:
aspart, glulisine, lispro
Regular
Neutral protamine Hagedorn
Glargine
Detemir
17
Onset
Peak
Duration
5–15 min
1–2 h
4–6 h
30–60 min
2–4 h
2–4 h
2h
2–3 h
4–10 h
Relatively flat
Relatively flat
6–10 h
12–18 h
Up to 24 h
Up to 24 h
18
Revisiting Inpatient Hyperglycemia
Table 2. Calculating the dose of scheduled insulin therapy
1. Obtain patient weight
2. Multiply body weight (in kg) by 0.2–0.5 U/d to obtain total daily insulin dose
a. Lean patients with newly recognized hyperglycemia or with type 1 diabetes: Start with 0.2–0.3 U/kg daily
b. Overweight patients with blood glucose level 140–200 mg/dL (7.8 to 11.1 mmol/L): Start with 0.3–0.4 U/kg daily
c. Obese patients
i. With type 2 diabetes and blood glucose level <140–200 mg/dL (7.8 to 11.1 mmol/L): Start with 0.4 U/kg daily
ii. With type 2 diabetes and receiving high doses of glucocorticoids and blood glucose level <200 mg/dL (11.1 mmol/L):
Start with 0.5 U/kg daily
3. Distribute total calculated dose as approximately 50% basal insulin and 50% nutritional insulin
a. Nutritional component divided by 3 to achieve premeal dose in patients who are eating
b. Nutritional component divided by 4 and administered every 6 hours in patients receiving continuous enteral nutrition
Approximately 50% of the calculated dose is administered as
basal insulin and 50% as prandial or nutritional insulin, in
divided doses. Adjustments in insulin doses are based on
results of bedside glucose monitoring to achieve glycemic targets and minimize the risk for hypoglycemia.43 Another
method for calculating the total daily insulin dose involves
determining the amount of correction insulin administered
over the preceding 24 hours and distributing this into basal
and nutritional components.
Higher doses of insulin often are required for patients
receiving high doses of glucocorticoids. The timing of anticipated elevations in blood glucose levels often corresponds to
the peak time of action of the steroid preparation used. For
example, patients who receive short-acting hydrocortisone will
have a greater insulin requirement for the next 6 to 12 hours,
whereas those treated with long-acting dexamethasone can
have a more prolonged increase in insulin requirements, with
a greater effect on postprandial excursions.41,45,46 Although the
optimal glycemic management strategy for these patients has
not been clearly defined, insulin is the preferred therapy in
the hospital.46 Gradual persistent adjustments in insulin
according to results of point-of-care blood glucose measurements can help avoid severe hyperglycemia.44,47 Standardizing
diabetes flow sheets and their location in the medical record
between hospital nursing units is essential.
For patients with no history of diabetes, blood glucose
monitoring with administration of insulin using a correction
insulin scale can be initiated. For patients previously treated
with insulin, the correction scale can be advanced in combination with anticipatory increments of approximately 20% in
doses of scheduled basal and bolus insulin therapy. Ongoing
adjustments can be made according to correctional insulin
requirements.47 To avoid hypoglycemia, it is important to
anticipate decreases in insulin doses with downward titrations
or discontinuation of steroid therapy.
The use of scheduled insulin therapy in patients receiving
enteral nutrition also poses unique challenges,39 including unanticipated dislodgement of feeding tubes, temporary discontinuation of nutrition because of nausea or for diagnostic testing, and
cycling of enteral nutrition with oral intake in patients whose
appetite is inconsistent.48 The use of a rapid-acting or shortacting insulin given at 4- to 6-hour intervals with or without an
intermediate- or long-acting insulin is suggested for controlling
glucose during enteral nutrition therapy while concurrently minimizing risk for hypoglycemia.30 In a recent study, glargine was
administered in combination with sliding-scale insulin to achieve
an average blood glucose level of 166 mg/dL (9.2 mmol/L), with
a low incidence of hypoglycemia.38 Approximately 50% of
patients in a comparison group treated with sliding-scale insulin
alone required the addition of an intermediate-acting insulin to
achieve similar glycemic control.38
Continuous SC insulin
infusion pumps
The number of outpatients who use continuous SC
insulin infusion (CSII) pumps for glycemic management is
growing, thereby increasing the likelihood that these patients
will be encountered in the hospital.49 Patients who use CSII
pumps in the outpatient setting are candidates for diabetes
self-management when they are hospitalized if they have the
mental and physical capacity to do so.30,50 However, many
nurses and physicians are uncomfortable allowing patients to
use a technology with which they have limited familiarity.51 As
a result, treatment of these patients when they are admitted
to the hospital varies.34
Some hospitals have established protocols to guide inpatient
insulin pump therapy and provide support for patients who have
the desire and ability to self-manage while hospitalized.52,53 In a
hospital with an established CSII protocol, mean glucose values
were similar for patients who continued and those who discontinued pump therapy. However, the frequency of hypoglycemia
(blood glucose level < 70 mg/dL [3.9 mmol/L]) was significantly
lower among those who continued CSII.52
The ability of a hospitalized patient to self-manage diabetes
care is a key component of the safety and efficacy of a CSII
pump protocol because it is not reasonable to assume that
Revisiting Inpatient Hyperglycemia
hospital staff nurses will be familiar with the functionality of all
currently available pumps.53 The availability of hospital personnel
familiar with CSII therapy to assist with adjustments in insulin
administration is essential to an effective inpatient program.
Patients who cannot continue CSII because of mental or
physical impairments can be switched to scheduled SC insulin.
The dose of long- or intermediate-acting insulin approximates the
total 24-hour basal insulin infused with CSII. For example, a
patient whose hourly CSII basal rate is 0.6 U/h would be
switched to 14 U of long- or intermediate-acting insulin, administered once or twice daily in divided doses. The prandial insulin
dose approximates the doses administered while the patient was
using CSII. If this information is not known, weight-based calculation of insulin doses can be performed (Table 2).
Other elements of CSII safety include measures that
some hospitals have taken, such as mandatory endocrinology
consultation and the deployment of policies or a “contract”
signed by patients that stress the importance to the patient of
nurse notification for boluses and rate changes to enable documentation for flowsheet purposes.
Insulin pens
Several institutions have transitioned from vials to patientspecific insulin pen devices as a way to reduce the risk for errors
and needle-stick injuries. Pen devices with safety autocovers have
the potential to reduce the risk for needle-stick injuries. The presence of a window on the pen device, allowing direct visualization
of the number of units being administered, has the potential to
reduce dosing errors. Certain factors favor this practice and others
warrant caution. A favorable aspect of this practice is the
increased use of insulin pens in the outpatient setting. The availability of pen devices in the hospital can facilitate patient education for insulin administration using these devices, decreasing the
need for separate education at the time of hospital discharge.
Nurses who learn to appropriately use the pens can educate
patients on using them at home. The insulin volume in pens is
less than that in vials, which may yield cost advantages for
patients with short hospital stays or low insulin requirements.54,55
Areas that warrant caution for introducing insulin pens for
hospital use relate to the portability of these devices, which
make them easy to use in more than one patient. This practice,
along with using these devices to “draw up” an insulin dose with
a syringe, has been observed, presenting the need to test
patients for associated infections.56 Because many nurses are
unfamiliar with these devices, education and surveillance of
nursing personnel are mandated, with demonstration of competency before the pens can be introduced for hospital use.
Suggestions for safe introduction of these devices include
oversight by a multidisciplinary committee, the introduction of
one device at a time, initial and follow-up nurse education,
the availability of nursing personnel knowledgeable in diabetes
management, and a requirement for initial and periodic testing of proficiency and competency.
Oral and injectable
noninsulin agents
Although insulin is the agent of choice for the timely
management of hyperglycemia in the hospital, oral and
injectable noninsulin glucose-lowering agents may be appropriate for some patients who are not critically ill, such as
those who ingest regular meals and do not have contraindications to these agents.1,30,42 Use of these agents is limited to
stable patients who used these medications before admission
or those with mild hyperglycemia.30,42 The pharmacokinetics
of the available oral and injectable noninsulin hypoglycemic
agents are not conducive to rapid titration to achieve desired
glycemic targets in most acutely ill patients.1,30,42
There are 5 classes of oral agents and 2 classes of
injectable noninsulin therapies for treating diabetes (Table 3).
Each drug class has significant limitations associated with
inpatient use.
Table 3. The 5 classes of oral agents for type 2 diabetes
Class
Mechanism of action
Side effects
Agents
Sulfonylureas
Short-acting insulin
secretagogues
Biguanides
Stimulate insulin production
Hypoglycemia
Glyburide, glipizide, glimepiride,
repaglinide, nateglinide
Decrease gluconeogenesis
Increase insulin sensitivity
Reduce insulin resistance
Nausea; diarrhea,
lactic acidosis (rarely)
Edema; congestive heart
failure; increased abnormalities
on liver function tests
Bloating; abdominal discomfort,
diarrhea
Upper respiratory tract infection,
nausea
Metformin
Thiazolidinediones
α-Glucosidase
inhibitors
Dipeptidyl
peptidase-4
inhibitors
Decrease rate of
carbohydrate absorption
Prolong action of
glucagon-like peptide-1
Increase insulin release
Decrease glucagon
19
Rosiglitazone, pioglitazone
Acarbose, miglitol
Sitagliptin
20
Revisiting Inpatient Hyperglycemia
Sulfonylureas are long-acting insulin secretagogues that can
cause severe and prolonged hypoglycemia in patients who are
elderly, who have reduced or limited oral intake, or who have
declining renal function.57–59 There are no data on hospital use
of the short-acting insulin secretagogues repaglinide and
nateglinide. These agents may have an advantage over sulfonylureas because they are administered before meals and can be
held for patients who are not eating. However, the risk for hypoglycemia may be similar to that with sulfonylureas in the outpatient setting, suggesting caution in the inpatient setting.60
Metformin is contraindicated with any decline in renal
function, such as that occurring with administration of IV
contrast dye, which increases risk for lactic acidosis.61
Hospital protocols to screen for this medication before dye
studies are requisite. Risk factors for lactic acidosis in
metformin-treated inpatients include cardiac disease, decompensated congestive heart failure, hypoperfusion, renal insufficiency, advanced age, and chronic pulmonary disease.62 Lactic
acidosis is a rare complication in the outpatient setting. In the
inpatient setting, the risks for hypoxia, hypoperfusion, and
renal insufficiency are much higher, making it prudent to discontinue metformin therapy in many patients.42
Thiazolidinediones exert their hypoglycemic effect primarily by improving peripheral insulin sensitivity. It can take several weeks for the full hypoglycemic effect to be realized, limiting the usefulness of these agents for achieving glycemic
control in the hospital. These agents must be discontinued in
patients who were receiving them before admission if they are
admitted with congestive heart failure, hemodynamic instability, or evidence of hepatic dysfunction.60
Pramlintide, exenatide, and the dipeptidyl peptidase
inhibitors act primarily to reduce postprandial blood glucose
excursions, and therefore are not appropriate for patients who
are not eating or have reduced oral intake. Pramlintide and exenatide are administered by injection and are associated with a
high frequency of nausea and vomiting.63 There is limited experience, and no published data, on the inpatient use of these
agents. The higher incidence of urinary and respiratory infections reported with the dipeptidyl peptidase-4 inhibitors argues
against initiation of these agents in the hospital because of the
potential increased risk for hospital-acquired infections.64
In summary, each major class of noninsulin glucose-lowering agents has significant limitations for inpatient use.
Moreover, they provide little flexibility or opportunity for titration in a setting in which acute changes often demand these
characteristics. Therefore, when used properly, insulin is preferred for most hyperglycemic patients in the hospital setting.
However, the need for continued insulin therapy must be
addressed at the time of hospital discharge with a thorough
medication reconciliation process.
What measures define
good glucose control?
As hospitals move forward with glycemic management
programs, a method for tracking the quality and safety of
these interventions is desirable but complicated.65,66 Unlike
other quality-of-care measures, any procedure used to define
good glycemic control in a hospital setting is complicated by
the number of blood glucose measurements obtained, the difficulty in coordinating these measurements with meals and
insulin doses, the accuracy of the point-of-care bedside meter
being used, and the availability of these data by the hospital
laboratory. In critical care units, each patient receiving an IV
insulin infusion may have up to 24 glucose measurements in a
24-hour period. In non–critical care areas, each patient may
have 4 to 6 measurements in this same period. Further complicating these efforts are decisions to use laboratory glucose
measurements, point-of-care bedside glucose measurements,
or both to measure glycemic control in an institution.67
For an individual patient, determining the adequacy of
glycemic control during hospitalization is straightforward.
Glycemic excursions above or below the desired range often
can be readily explained by knowledge of missed meals or by
obtaining a sample soon after a meal has been ingested. From
a retrospective or institutional perspective, knowledge of these
events often is not available. Chart review is time-consuming
and not always revealing. There is also a need to differentiate
admission glucose levels from those obtained once the health
care team has intervened and provided care.
Despite these obstacles, it is important for hospitals to
devise a system for monitoring the safety and efficacy of a
glycemic management program. To establish this, there must
be clear glycemic distinctions between hypoglycemia, desired
blood glucose values, and hyperglycemia. Inpatient hypoglycemia is defined as any blood glucose level less than
70 mg/dL (3.9 mmol/L), and severe hypoglycemia denotes any
blood glucose level less than 40 mg/dL (2.2 mmol/L).1
Although hyperglycemia is defined as glucose values greater
than 140 mg/dL (7.8 mmol/L), this is used to define the point
at which therapy is considered. With the defined goal range
for blood glucose levels in the hospital of 140 to 180 mg/dL
(7.8 to 10.0 mmol/L), the level for defining hyperglycemia for
quality assurance purposes starts at greater than 180 mg/dL
(10.0 mmol/L). Some institutions differentiate between mild
to moderate (blood glucose level, 180 to 300 mg/dL [10.0 to
16.6 mmol/L]) and severe (blood glucose level > 300 mg/dL
[16.6 mmol/L]) hyperglycemia.68
By using these categories of glycemic control, an institution can determine the percentage of blood glucose measurements that fall within each range, and track these over time
by service or nursing unit.66,68 Some caution must be used in
determining the frequency of glucose measurements outside
desired ranges because more frequent monitoring occurs with
hypoglycemia or hyperglycemia. To avoid overcounting these
events, refinement of data sets to define a single peak or
nadir blood glucose value within prespecified time intervals
(for example, 4 hours) can be useful for more accurately
measuring the frequency of glycemic excursions.19 It is also
important to regularly review cases of severe hypoglycemia
and hyperglycemia as a way to determine potential factors
that may have contributed to the event and that can be prevented in the future. It is through this type of analysis that
Revisiting Inpatient Hyperglycemia
institutions can modify and improve efforts directed at
improving glycemic control.
On a national level, appropriate management of hyperglycemia during the postoperative period is part of the
Surgical Care Improvement Project (www.qualitymeasures
.ahrq.gov). This initiative mandates early-morning blood glucose levels of 200 mg/dL (11.1 mmol/L) or less on the first
2 postoperative days as a way to minimize the risk for postoperative infection.69 The program is based on evidence of a
3-fold increase in risk for any postoperative infection and a
6-fold increase in risk for severe infection in patients with
postoperative blood glucose values greater than 220 mg/dL
(12.2 mmol/L).70
Patient harm can occur with both hypoglycemia and hyperglycemia. Severe glycemic excursions that occur during hospitalization are now categorized as “never events” by the National
Quality Forum. This means that third-party payors, including the
Centers for Medicare & Medicaid Services, will withhold any
additional payments to hospitals for care related to these events.
Other measures that have been adopted by some institutions as a way of ensuring or improving the safety of their
glycemic management program include limiting the hospital
formulary to avoid confusion; performing medication reconciliation with careful recording of insulin types and doses at time
of hospital discharge; avoidance or prohibition of the use of
the abbreviation “U” in place of “units” for insulin; and coordinating delivery of meal trays with point-of-care blood glucose
monitoring and administration of bolus insulin.
Summary
The glycemic targets outlined in the AACE/ADA consensus
statement are achievable with a rational approach to insulin
therapy in critical care and non–critical care areas of hospitals.
Intravenous insulin infusion protocols with demonstrated safety
and efficacy offer advantages to achieve these goals in critical
care areas. Transition to SC insulin is recommended with discontinuation of these infusion protocols to avoid rebound hyperglycemia. Outside critical care areas, scheduled SC insulin with
a basal and prandial or nutritional (that is, bolus) component is
effective for achieving glycemic control. Correction insulin can
be used in combination with basal–bolus insulin to treat
glycemic excursions above the desired range. Staff education,
the development of point-of-care meters that provide reliable
and reproducible blood glucose measurements, appropriate
administration of insulin, and careful implementation of standardized protocols are essential elements of a successful inpatient glycemic management program.
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Med. 1999;16:586-90. [PMID: 10445835]
58. Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR.
Metformin, sulfonylureas, or other antidiabetes drugs and the
risk of lactic acidosis or hypoglycemia: a nested case-control
analysis. Diabetes Care. 2008;31:2086-91. [PMID:
18782901]
23
59. Gonzalez RR, Zweig S, Rao J, Block R, Greene LW. Octreotide
therapy for recurrent refractory hypoglycemia due to
sulfonylurea in diabetes-related kidney failure. Endocr Pract.
2007;13:417-23. [PMID: 17669721]
60. Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos
S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern
Med. 2007;147:386-99. [PMID: 17638715]
61. Calabrese AT, Coley KC, DaPos SV, Swanson D, Rao RH.
Evaluation of prescribing practices: risk of lactic acidosis with
metformin therapy. Arch Intern Med. 2002;162:434-7. [PMID:
11863476]
62. Dunham DP, Baker D. Use of an electronic medical record to
detect patients at high risk of metformin-induced lactic acidosis.
Am J Health Syst Pharm. 2006;63:657-60. [PMID: 16554290]
63. Krentz AJ, Patel MB, Bailey CJ. New drugs for type 2 diabetes
mellitus: what is their place in therapy? Drugs. 2008;68:213162. [PMID: 18840004]
64. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis.
JAMA. 2007;298:194-206. [PMID: 17622601]
65. Cook CB, Moghissi E, Joshi R, Kongable GL, Abad VJ.
Inpatient point-of-care bedside glucose testing: preliminary data
on use of connectivity informatics to measure hospital glycemic
control. Diabetes Technol Ther. 2007;9:493-500. [PMID:
18034603]
66. Goldberg PA, Bozzo JE, Thomas PG, Mesmer MM, Sakharova
OV, Radford MJ, et al. “Glucometrics”—assessing the quality of
inpatient glucose management. Diabetes Technol Ther.
2006;8:560-9. [PMID: 17037970]
67. Hoofnagle AN, Peterson GN, Kelly JL, Sayre CA, Chou D,
Hirsch IB. Use of serum and plasma glucose measurements as
a benchmark for improved hospital-wide glycemic control.
Endocr Pract. 2008;14:556-63. [PMID: 18753097]
68. Blank GE, Korytkowski M, Virji MA. Computerized model of
bedside glucose monitoring contributes to the successful
implementation of an inpatient diabetes management program
in a university hospital. Point of Care. 2009;8:1-5.
69. Brendle TA. Surgical Care Improvement Project and the perioperative nurse’s role. AORN J. 2007;86:94-101. [PMID:
17621450]
70. Pomposelli JJ, Baxter JK 3rd, Babineau TJ, Pomfret EA, Driscoll
DF, Forse RA, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. JPEN J
Parenter Enteral Nutr. 1998;22:77-81. [PMID: 9527963]
24
Revisiting Inpatient Hyperglycemia
Chapter 4
Transitioning Patients Along the
Continuum of Care—Intravenous
to Subcutaneous Insulin,
Inpatient to Outpatient Settings:
Practical Considerations
By Marie E. McDonnell, MD, and Marina Donahue, MS, NP, CDE
In most cases, transitioning from an insulin infusion to a subcutaneous regimen represents a step forward in care and often is
interpreted as “progress” toward successful discharge. Patients
who are ready to be transitioned often are rapidly recovering from
severe illness. In many cases, the impetus for transition is discontinuation of mechanical ventilation or vasopressor support.
However, a rushed or unplanned transition may result in hyperglycemia that can require substantial time to correct.1 This often
causes a frustrating setback for the patient. A common temptation
is to discontinue insulin infusions and begin “sliding-scale” insulin
alone, an approach known to be inferior to combination treatment
with individually tailored basal and rapid-acting insulin.2
Health professionals who care for inpatients requiring treatment for abnormal glucose levels must understand that the simplest way to determine a safe and effective subcutaneous insulin
program is to calculate doses from a variable-rate patient-tailored
infusion. Transitioning from intravenous insulin infusions used
in higher-level care settings to subcutaneous insulin regimens for
use on general medical surgical floors is not difficult. Moreover,
transitions can have a major impact on how well a patient recovers from illness. This is demonstrated most clearly in reports
describing the benefits of extending glycemic control beyond the
acute phase of illness (for example, after myocardial infarction3
or cardiothoracic surgery4,5).
When during the hospital
stay do patients become
eligible to transition from
intensive insulin infusion
therapy to subcutaneous
methods?
The normal pancreas responds to continuous nutrition
and carbohydrate intake by releasing insulin in 10 to 20
oscillating pulses during a 24-hour period.6 Although insulin
by intravenous infusion is the only method that comes close
to mimicking this physiologic requirement, it is not practical (and may be unsafe) for the patient who is no longer
critically ill, is receiving scheduled nutrition (for example,
meals or enteral feeding), or is preparing for discharge from
the hospital.
There are 2 general principles behind a safe and effective
transition from intravenous to subcutaneous insulin:
1. The 24-hour insulin requirement is extrapolated from
an appropriately selected hourly insulin rate.
2. The subcutaneous insulin program is designed to fit
the patient’s nutrition program and other complicating factors
(such as glucocorticoid exposure).
To apply these principles, it is necessary to select appropriate patients. Patients suitable for this transition ideally have
a stable infusion rate (within ± 0.5 U) and blood glucose levels in goal range for at least 4 hours before the transition.
Patients also should be well enough to eat scheduled meals or
be receiving enteral or parenteral feedings at a stable rate
(with no imminent plans to decrease or increase the rate).
Transition should be delayed under certain circumstances,
most importantly for patients who are in the active phases of
critical illness (for example, those receiving vasopressors) or who
are just beginning to recover from ketoacidosis.
Such patients can have rapidly changing, unpredictable
insulin requirements,7 such that premature estimates of
insulin requirements yield poor results—particularly hypoglycemia. In addition, patients requiring high insulin doses
while receiving the infusion (for example, >6 U/h) at the
time of transition should be evaluated for overfeeding or
resolving stressor before transition doses are calculated.
Transition should be deferred until insulin requirements
are reduced, unless it is clear, after careful assessment,
that the patient is otherwise appropriate and should benefit
from the transition.
Revisiting Inpatient Hyperglycemia
Calculating the
subcutaneous insulin
transition dose
The ultimate insulin regimen should address the 3 components of insulin requirement: basal (what is required in the
fasting state to maintain normal metabolism), nutritional
(what is required for peripheral glucose disposal), and correctional (what is required for unexpected glucose elevations).
For patients who are not receiving significant calories, the
infusion rate represents the basal insulin requirement. Some
published strategies that are used to “find” the basal dose
involve estimating a 24-hour insulin requirement and distributing it into basal and nutritional insulin to maintain glucose
in the optimal range.8 However, with heightened concerns
about the risk for hypoglycemia during acute illness, and
recent support for more moderate glycemic control in the hospital, strategies that consider the most recent insulin requirements may be better tailored to the recovering patient. Studies
in inpatient critical care areas have determined successful
dose-finding strategies by extrapolating 24-hour doses from
insulin infusion rates over the past 6 hours.
In a study conducted in the surgical intensive care unit,9 the
24-hour insulin requirement was calculated by taking the total
amount of insulin infused within the past 6 hours and multiplying by 4. Of note, the insulin was infused while the patient was
not receiving significant calories, so the infusion rate represented
the “fasting” insulin requirement. In this study, a safe and effective basal insulin dose for the subsequent 24 hours was calculated as 80% of this estimated requirement. Other percentages were
compared to 80% (such as 40% and 60%), but 80% resulted in
more glucose values of 80 to 150 mg/dL (4.4 to 8.33 mmol/L)
without more hypoglycemia. The extrapolated basal dose can be
given in 1 long-acting insulin dose (for example, detemir or
glargine) or split in half and given in 2 moderate-acting insulin
doses 12 hours apart (for example, neutral protamine Hagedorn
insulin). Insulins that are short- (regular) or rapid-acting (aspart,
glulisine, or lispro) can be added as needed depending on nutritional status and glucose levels. The total daily nutritional insulin
requirement approximates the total basal requirement10 and can
be divided into doses according to the nutritional plan.
Case example 1
A 48-year-old woman is ready to eat 36 hours after coronary artery bypass graft surgery. Between 1 a.m. and 7 a.m.,
she was receiving an average of 2 units of intravenous regular
insulin per hour, with a glucose level of 130 to 150 mg/dL
(7.2 to 8.3 mmol/L). She was given a small amount of juice at
7 a.m., and her glucose level increased to 195 mg/dL, prompting an increase in the infusion rate to 3 U/h. Using the fasting
overnight rate of 2 U/h, the total basal insulin requirement is
calculated as (2 × 24 [80%] = 42 [0.8] = 34 units). The 34
units is given as detemir or glargine insulin 2 hours before discontinuation of the insulin infusion: 1.5 (hourly rate) × 20
(equivalent to taking 80% of 1.5 × 24 hours) = 30 U. Because
the patient is expected to eat at the next mealtime, nutritional
25
insulin is ordered as aspart, lispro, or glulisine to be given at
each meal, within 15 minutes before or after the first bite of
food. Although this rapid-acting analogue daily requirement is
expected to be as high as 34 U per day, split into 3 doses of
10 to 12 U per meal, the rapid-acting insulin dose is started at
6 U with each meal until the patient is eating well (for example, >50% of meal). Nursing is instructed to hold the rapidacting insulin if the meal is missed or the glucose level is low
(for example, <70 mg/dL [3.9 mmol/L]). Correctional insulin
is ordered to be added if the glucose level exceeds the target
glucose range.
For patients receiving continuous enteral feedings or total
parenteral nutrition, the insulin infusion accounts for basal,
nutritional, and correctional insulin. In this case, one can
determine the 24-hour insulin requirement by the same
method; however, instead of administering it as a basal insulin
injection, the requirement should be distributed, for example,
as 50% basal and 50% nutritional or in a somewhat different
distribution depending on the patient. After a dose of both
basal and nutritional insulin, the infusion can be discontinued
in 1 hour because the nutritional insulins reach adequate
plasma levels within 1 hour.
Case example 2
A 72-year-old man with type 2 diabetes is ready to leave
the intensive care unit after recovery from urosepsis. He is no
longer receiving vasopressors, is breathing on his own, and is
receiving continuous enteral feedings. Glucose values have
ranged from 120 to 160 mg/dL (6.7 to 8.9 mmol/L) for the
previous 6 hours, with an average intravenous insulin infusion
rate of 3 U/h during this time. The total daily insulin requirement is calculated as (3 U/h × 24) (80%) = 72 (0.8) = 58 U of
insulin per day. The 58 U is distributed approximately as 29 U
(50%) of basal insulin given as a 1-time dose of basal insulin,
and 29 U (50%) of nutritional insulin, split into 4 doses per
day given every 6 hours. Because nutritional insulin is easily
titrated more than once daily, the initial dose is given as 6 U
and is administered along with supplemental correction
insulin as needed every 6 hours. The basal insulin is administered at the same time as the short-acting insulin dose, and
the insulin infusion is discontinued 1 hour later.
Key to success:
Writing the orders
As noted in these case examples, to prevent the recurrence of hyperglycemia, the insulin infusion and the subcutaneous insulin must overlap because the duration of
insulin effect when given intravenously is less than 1 hour.
Because of the time required for subcutaneous basal insulin
to reach adequate levels in the bloodstream, an insulin infusion should be discontinued 2 hours after a basal dose is
given, or 1 hour after the administration of a rapid- or shortacting insulin. Start by writing 1-time orders for the transition itself. For example, for the patient administered only
basal insulin at transition, you would note “detemir insulin
26
Revisiting Inpatient Hyperglycemia
20 units. Give ×1 now and stop the infusion 2 hours after
injection.” For patients receiving continuous enteral nutrition, you may opt to give both the basal and nutritional
insulin at the same time and stop the infusion 1 hour later
(see case example 2).
As discussed by Korytkowski in the previous chapter
(page 15), the language used to instruct nursing staff on how
to dose insulin is crucial to the safety and effectiveness of an
insulin regimen prescribed in the hospital. Nutritional insulin
doses, for example, should be held if the nutrition is not
administered (for example, the meal is missed or the enteral
feeding is held). Specialized insulin order sets are key to standardizing this language and simplifying insulin therapy for the
nursing staff across entire hospital systems.
Subsequent insulin doses in the days following transition
should be adjusted according to patient response and clinical
status. If a patient continues to improve clinically, insulin
requirements may decline, which can occur rapidly. Any glucose value below goal range in the 24 hours after transition
should prompt down-titration of insulin dosing. Likewise, if
the glucose level is elevated, it is reasonable to consider that
the initial doses may have been too conservative. Alternatively,
a patient’s recovery may be interrupted by a complication that
requires continued critical care. In this case, it is wise to
return to the variable-rate continuous insulin infusion therapy
until the patient improves clinically. Close physician oversight
is required.
Stress-induced
hyperglycemia:
management and
future risk
Hyperglycemia newly recognized in the hospital is common.11 Several studies have shown this group to be a higher-risk population, with greater mortality rates and more
complicated hospitalizations. In an important retrospective
analysis of hospital admissions in an academic urban hospital, hyperglycemia (glucose level >200 mg/dL [11.1 mmol/L])
was present in 38% of patients at some point during the
hospitalization, yet a third of these patients had no history
of diabetes before admission. This newly discovered hyperglycemia was associated with a higher in-hospital mortality
rate (16%) compared with patients with documented diabetes (3%) and normoglycemia (1.7%). This stress-induced
hyperglycemia was also found to be a marker for more complicated inpatient stays.
This risk for postdischarge abnormal glucose metabolism
after hyperglycemia in the hospital has been found to be as
high as 65% among patients who have had myocardial infarction.12 Because hyperglycemia may be transient and situational, diabetes cannot be diagnosed in the hospital by using commonly accepted criteria.13 Therefore, obtaining a reliable
hemoglobin A1c (HbA1c) level as part of the evaluation of
Table 1. Discharge planning for inpatients with hyperglycemia: suggested use of
the hemoglobin A1c
Variable
Unknown diabetes
Known diabetes
HbA1c <6.5%*
Assess diabetes risk factors;
counseling and outpatient
screening within 1 mo
Assess for hypoglycemia risk;
continue prehospital regimen
unless new safety concerns arise
HbA1c 6.5%–7%*
and insulin
requirement
<0.4 U/kg per d
Counseling and outpatient
screening within 1 month,
with or without
pharmacologic prevention†
HbA1c 6.5%–7%*
and insulin
requirement
≥0.4 U/kg per d
Counseling and initiation
of appropriate
diabetes treatment plan
HbA1c >7%*
Counseling and initiation
of appropriate
diabetes treatment plan
Follow-up
Communicate recommendation
to outpatient providers;
address need for referral
to multidisciplinary care for
diabetes treatment or prevention
Assess for hypoglycemia risk;
Communicate recommendation
continue prehospital regimen
to outpatient providers;
unless new safety concerns arise
address need for referral
to multidisciplinary care for
diabetes treatment or prevention
Assess for hypoglycemia risk;
Communicate recommendation
continue prehospital regimen
to outpatient providers;
unless new safety concerns arise
address need for referral
to multidisciplinary care for
diabetes treatment or prevention
Consider transient effect of
Communicate recommendation
subacute illness before
to outpatient providers;
hospitalization on HbA1c;
address need for referral
consider advising augmentation
to multidisciplinary care for
of outpatient regimen to target <7% diabetes treatment or prevention
* HbA1c = hemoglobin A1c. The HbA1c is inaccurate after blood transfusion and in patients with severe anemia, or in those with high or low red
blood cell turnover states.
† Metformin (Diabetes Prevention Program trial36), thiazolidinedione (Diabetes REduction Assessment with ramipril and rosiglitazone Medication
trial37), and acarbose.38
Revisiting Inpatient Hyperglycemia
hyperglycemic patients in the hospital is increasingly favored
by some clinicians.14 The HbA1c is an accurate indicator of
glycemic control for 2 to 3 months. The American Diabetes
Association has reported that adequate glycemic control is
associated with an HbA1c value less than 7% (American
Diabetes Association clinical guideline 2009)13 or 6.5% or less
(American Association of Clinical Endocrinologists guidelines).15 An HbA1c value can be obtained before planned hospitalization or early in a hospital stay to help direct discharge
planning (Table 1). Obtaining the HbA1c value before planned
surgery (for example, in patients with diabetes or those at risk
for postoperative hyperglycemia) may have a 2-fold benefit: 1)
to help optimize glycemic control before hospitalization and 2)
to guide treatment recommendations upon discharge.16
Although use of the HbA1c is not recommended by all expert
societies, increasing attention is being given to standardizing
this measurement to allow it to be a diagnostic tool. An international working group recently published a report advocating
the use of HbA1c for diagnosis, although this has not yet been
accepted as standard practice. The group’s statement suggested that an HbA1c of 6.5% or greater could be a reasonable
diagnostic threshold for diabetes17 because this level of hyperglycemia is associated with an increased risk for microvascular
disease. Hemoglobin A1c levels between 6.1% and 6.4% are
also not considered normal, and this may correlate with
impaired fasting glucose or impaired glucose tolerance.
Although consensus guidelines are evolving to incorporate
HbA1c into diagnostic criteria, alternative criteria, such as the
following, can be used to identify diabetes in hyperglycemic
inpatients: HbA1c greater than 6.5% and significant insulin
requirement after resolution of the acute phase of illness,
which may represent a total daily dose of 0.4 U/kg.18 For such
patients, it is reasonable to initiate a diabetes treatment plan
in conjunction with outpatient providers. However, these
patients require rapid outpatient follow-up, and those not prescribed a specific therapy should have confirmatory diabetes
screening performed within 1 month of discharge. Outpatient
therapy should be based on standard practice, including
HbA1c15,19 and other factors that suggest a specific type of
diabetes.20
The key element here is that hospitals need to design a
systematic approach to screening patients with HbA1c and not
rely on clinician memory for this. Protocols and order sets that
contain this test are more likely to result in higher screening
and diagnosis rates.
Because hospitalizations for acute illness usually are
shorter than 5 days,21 discharge planning for the patient with
diabetes in the hospital ideally begins on day 1 of admission.
Many factors must be considered in designing the outpatient
management plan (including evaluation of the patient’s skill
set); thus, starting the transition process early in admission is
extremely helpful for the patient and the many providers
required to make the plan successful.10 Patients who have any
of the following risk factors for a challenging discharge plan
should receive a consultation from a certified diabetes educator before discharge (when and where available)22,23 and early
during the admission: impaired cognition, low literacy or
27
Table 2. Survival skills to be taught
before discharge
Basic understanding of what diabetes is
Self-monitoring of blood glucose and understanding results
How and when to take diabetes medications
Recognition, treatment, and prevention of hypoglycemia
Basic knowledge of food’s effect on glucose levels
What to do during illness
How to dispose of lancets and insulin syringes
Adapted from Moghissi ES, et al. Endocr Pract. 2009;15:353-69.2
numeracy,24 poor vision, poor dexterity (such as after a stroke),
homelessness, or severe poverty.
Although the task of teaching diabetes in a hospital environment can be challenging because of the nature of acute care
(frequent interruptions, limited time, distractions related to
pain), the basics of diabetes pertinent to the patient can be
taught effectively through the design of an inpatient diabetes
service.22,23 The incorporation of an advanced practice registered
nurse, nurse practitioner, or physician assistant with certification
in diabetes education into the inpatient diabetes care team has
been shown to offer a high level of comprehensive patient care
for diabetic patients.22,23 Also helpful is inclusion of other multidisciplinary members of the health care team, such as clinical
pharmacists. Hospitals should recognize the unique opportunity
afforded patients for the above education. Relative to the chaotic
primary care setting, a coordinated inpatient education program
may yield tremendous gains for improvement of ongoing diabetes care after discharge.
Initial assessment by a trained diabetes educator or discharge planner can include basic feasibility of diabetes management in the home setting: Can the patient prepare his or
her own meals? Can the patient self-monitor blood glucose at
the prescribed frequency? Can the patient take his or her diabetes medications or insulin accurately? Is there a family
member who can assist with tasks that the patient cannot perform? Is a visiting nurse needed to facilitate transition to the
home? The inpatient educator can be trained to identify
patients at higher risk for hypoglycemia, those who could have
more serious consequences from poor control, and those with
special situations warranting highly tailored regimens. This
includes patients with renal or liver impairment, pancreatic
insufficiency, or hypoglycemia unawareness; very elderly
patients; homeless patients; and patients with drug addiction.
Furthermore, added complexities of physical and visual
impairment, language barriers, or cultural differences require
a multifaceted approach to care. Diabetes education with selfmanagement is critical for the successful transition from hospital to home.25
A primary focus of (often brief) education sessions in the
hospital is on teaching “survival skills” (Table 2). Survival skills
28
Revisiting Inpatient Hyperglycemia
are crucial to safe practice at home and usually do not include
the detail required for intensive management. One of these
skills is blood glucose monitoring, including interpreting
results and when to call for help. Because many patients in
the hospital are at risk for subsequent illness, a clear discussion of how to manage medications and glucose testing on
“sick days” is critical. Also important is an understanding of
how to take diabetes medications (including insulin) and
awareness of hypoglycemia, including its treatment and prevention. Basic nutrition should also be incorporated into survival skills education, especially the clear identification of
carbohydrates versus fats versus proteins. For safe, competent
home management, the patient or family member must
demonstrate successful glucose monitoring and insulin administration. Survival skills may not be mastered if tackled only on
the day of discharge; that practice places patients and
providers at risk for serious error. Written instructions and
paper guides with illustrations can be useful26 and often are
part of a certified diabetes educator’s toolbox for teaching
patients to safely self-manage their condition.
Insulin therapy:
hospital to home
Insulin therapy, although always indicated for the hyperglycemic hospitalized patient, does not always “follow” a
patient home. Insulin is the safest practice for individuals
with changing insulin needs related to illness because it can
be titrated easily and has predictable action profiles. However,
for many patients receiving insulin in the hospital, the discharge diabetes regimen may be a combination of noninsulin
medications. If there is a reliable HbA1c measurement,
providers can opt to modify regimens to meet an HbA1c goal
(<7% in most patients), while considering any new contraindications to some agents (for example, renal insufficiency with
metformin therapy or congestive heart failure with thiazolidinediones). Recommendations for noninsulin agents after
discharge may be a relief for patients who have concerns
about continuing insulin therapy, yet the opportunity to identify those who would benefit from insulin therapy should not be
missed in the hospital. Patients requiring more than 0.4 U/kg
of insulin per day in the setting of an above-goal HbA1c, and
particularly if the HbA1c is greater than 10%, should be evaluated for insulin therapy after discharge. Use of 2 or more fully
titrated oral agents and an HbA1c value greater than 8.5%
should also prompt consideration of insulin therapy. A diabetes educator is optimally used to guide these patients
toward not only acceptance of insulin therapy but also the
practical design of a feasible insulin program. If a trained diabetes educator is not available, the patient’s nurse can assume
the role of educator to address several issues known to present
barriers to successful insulin therapy,27–29 including fear of
pain, weight gain, inconvenience, complexity, time concerns,
cost, and sense of failure. Accurate medication reconciliation
is paramount to ensure that patients who begin receiving
insulin while hospitalized do not also inadvertently resume all
of their previous oral hypoglycemic agents if those have been
discontinued.
Case study: inpatient diabetes education
Mr. S. is a non–English-speaking man, 52 years old, with
known insulin-treated diabetes who has had a stroke. His family members are unknown. He has significant hemiparesis,
hemianopsia, and aphasia. Mr. S. reveals that he is frightened
because of his inability to communicate due to a language
barrier and aphasia.
The inpatient nurse practitioner–certified diabetes educator joined a multidisciplinary team composed of a registered
nurse, pharmacist, occupational therapist, physical therapist,
social worker, and physician. Through use of a translator, it
was discovered that Mr. S. was illiterate. He could understand
what happened to him and was subsequently able to understand that he had to “relearn” how to care for his diabetes in
light of his disabilities. Retraining of diabetes survival skills
was started 3 days before discharge from the hospital. He was
trained on how to use a voice-modulated glucose meter and
was able to successfully administer insulin via an insulin pen
in place of vial and syringe. The hospital team assisted in
obtaining health care coverage.
Mr. S. was discharged to receive intensive inpatient rehabilitation, with instruction to continue education and evaluation. The inpatient pharmacist reviewed all discharge medications and instructions with both the patient and the physician.
The inpatient physician contacted the patient’s primary care
physician, who agreed with the plan and referred the patient
for follow-up with the outpatient diabetes education center to
solidify and monitor the individualized treatment plan.
Outpatient follow-up
Outpatient follow-up after hospitalization-related hyperglycemia, ideally within a multidisciplinary approach to diabetes care, has led to successful prevention of diabetes-related
complications if abnormal glucose tolerance persists.30–32 For
a successful transition from inpatient to outpatient care, the
inpatient providers should create a transparent link between
the inpatient plan and care at home. This includes direct
communication at the time of discharge with an outpatient
provider about the recommended treatment plan. Examples
include sending the primary care physician a copy of the discharge summary with a specific section dedicated to outpatient diabetes recommendation (either electronically or by
fax); calling the outpatient provider directly to discuss recommendations and concerns related to the patient’s success; and
contacting a certified diabetes educator to review concerns
identified in the hospital (such as problems with numeracy)
that can be targeted in a follow-up visit. Diabetes-targeted follow-up from the hospital for patients with hyperglycemia during illness should occur within 1 month after discharge.2
A major goal of rapid outpatient follow-up after hospitalization is to reevaluate the discharge regimen. Patients newly
receiving insulin therapy require more attentive follow-up.
Telephone conversations with the patient after discharge may
Revisiting Inpatient Hyperglycemia
help to prevent readmission. As noted, not all patients will
require insulin therapy after discharge. Patients who were
newly diagnosed with diabetes and discharged with an insulin
regimen may be switched to oral therapy.33,34 However,
patients moved to oral agents require close follow-up after discharge. If the HbA1c exceeds 7.0% after the switch, supplementation with insulin may be warranted, in addition to (or in
place of) part of the noninsulin diabetes regimen.15,19
Finally, stress-induced hyperglycemia in the hospital in
the setting of a normal or near-normal HbA1c (<6.5%), commonly called stress hyperglycemia,2 requires reassessment
after resolution of illness and resumption of usual outpatient
activities. These patients should be considered high risk for
overt diabetes; for practical purposes, and to avoid clinical
inertia, they should be counseled similarly to patients with
impaired fasting glucose or impaired glucose tolerance.
Depending on the risk factor profile of the patient, one may
recommend that a definitive test (such as oral glucose tolerance) be ordered by the patient’s outpatient provider. Risk factors that suggest a high likelihood of conversion to diabetes in
the next 6 to 12 months, and therefore drive more aggressive
postdischarge screening, include hypertension, hyperlipidemia, coronary artery disease, African-American or Hispanic
ethnicity, age 45 years or older, body mass index greater than
25 kg/m2, and family history or history of gestational diabetes.
Counseling should include presenting these diabetes risk criteria, and patients meeting any criterion ideally should be presented with specific preventive strategies, including aggressive
lifestyle modification (for example, exercise and weight loss of
5% to 10% of body weight if the patient is overweight) and
pharmacologic therapy.35 Lifestyle modification is the most
powerful tool to teach patients—organized regimens can
result in a 58% risk reduction for the development of type 2
diabetes.36 These efforts should be the first and last recommendation for patients with newly recognized hyperglycemia
in the hospital. Clinicians find motivational interviewing and
goal-setting techniques to be beneficial when counseling for
lifestyle modification.
Summary
Because any single patient can enter the hospital through
different points (for example, emergency department, planned
admission for surgery) and then transition through many levels
(such as intensive care unit or regular medical floor) or points
of care (for example, diagnostic procedures, surgery), as well as
have a changing status (for example, requiring medications
such as steroids or pressors; enteral or parenteral nutrition),
the management of patients with hyperglycemia throughout
their continuum of care can be challenging. In addition, the
complexity of management increases because of the many
causes of hyperglycemia: documented diabetes, newly discovered diabetes, or transient stress hyperglycemia. Thus, it is
important to identify the points of transition and safely and
effectively manage glucose levels throughout the points of care.
One can easily see that multidisciplinary education and awareness are critical. The inpatient setting is also an opportunity to
29
revisit the status of diabetes control in a patient or provide
patient education in a newly identified chronic disease state.
Diabetes education and planning for outpatient follow-up must
be considered part of the continuum of care during the hospitalization rather than simply something that occurs near the
time of discharge. Adequate follow-up and transition to the
outpatient provider are essential.
References
1. Malmberg K, Rydén L, Efendic S, Herlitz J, Nicol P,
Waldenström A, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic
patients with acute myocardial infarction (DIGAMI study):
effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:5765. [PMID: 7797776]
2. Moghissi ES, Korytkowski MT, DiNardo M; American
Association of Clinical Endocrinologists. American Association
of Clinical Endocrinologists and American Diabetes Association
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Revisiting Inpatient Hyperglycemia
31
INSTRUCTIONS FOR OBTAINING CME/CE CREDIT
Revisiting Inpatient Hypergylcemia: New Recommendations, Evolving Data,
and Practical Implications for Implementation
Project ID: 6651-ES-14
There are no fees for participating and receiving CME/CE credit for this activity. During the period December 15, 2009, through
December 31, 2010, participants must 1) read the learning objectives and faculty disclosures; 2) study the educational activity; and
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by project ID 6651-ES-14. After you register and successfully complete the post-test with a score of 70% or better and the evaluation, your certificate will be made available immediately.
Should you have questions regarding obtaining CME/CE credit, please contact:
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303-799-1930, x5286