Hear yea, hear yea, as I ring this bell,
Of the importance of glucose, in the hospital, shall we tell.
My colleagues, with whom I am here,
Shall fill you with interest and perhaps some fear.
For an elevated glucose in the hospital not only raises the bill,
But stands to make one more gravely ill.
Whether one has had diabetes before,
An elevated blood sugar one cannot ignore.
The questions we raise today in the “Taming of the Glu,”
we ask. The answers of how to do it…are not a simple task.
Practice recommendations regarding inpatient glucose control define hyperglycemia as a fasting plasma glucose (FPG) level ≥126 mg/dL or a casual blood glucose (BG) level ≥200 mg/dL.[1,2] These levels are also used as criteria for diagnosing diabetes, but not all hyperglycemic hospital patients have diabetes. Hyperglycemic patients in hospital settings fall into 3 categories: those with a medical history of diabetes, those with unrecognized diabetes that is confirmed after hospitalization, and those with hospital-related hyperglycemia that reverts to normal after discharge. Regardless of whether a patient has a previous diagnosis of diabetes, aggressive treatment of hyperglycemia has been demonstrated to reduce morbidity and mortality.[3,4,5,6,7] In a joint position statement, the American Association of Clinical Endocrinologists (AACE) and the ADA concluded that, "Unrecognized and untreated hyperglycemia is an ‘error of omission' as hyperglycemia creates an unsafe setting for the treatment of illness and disease."
Inpatient hyperglycemia places a high cost burden on the medical system. Longer hospital stays associated with hyperglycemia increase medical costs. One study demonstrated that, in diabetes patients undergoing coronary artery bypass graft (CABG) surgery, each 50 mg/dL rise in BG increased the postoperative stay by 0.76 days, increased hospital costs by $1769, and increased hospital charges by $2824. Although it may be expensive, the coordination of labor-intensive efforts to achieve tight glycemic control in the hospital setting can be cost-effective. Savings are realized through improved medical outcomes leading to decreased length of hospital stays, decreased infection rates, decreased readmission rates, and increased ability to generate more income by serving more patients per bed. Importantly, savings in hospitalization costs can be greater than the increased costs of intensive treatment relative to conventional treatment.
Inpatient hyperglycemia is also common. Studies by Umpierrez et al. and Levetan et al. found that hyperglycemia was present in 13% and 38% of hospital-admitted patients, respectively.[5,10] There are a number of causes for hyperglycemia during hospitalization, including corticosteroid therapy, decreased physical activity, and reluctance to use insulin therapy. Poorly controlled diabetes is also a significant contributing factor. Studies have identified 60% to 70% of hyperglycemic hospital patients as having diabetes.[5,10] A current, conservative estimate indicates that 12.4% to 25% of hospitalized adults have diabetes, and this number is growing. In the US from 1980 to 2003, the number of hospital patients discharged with a diagnosis of diabetes increased 234%, from 2.2 to 5.1 million, and the trend is expected to continue as the diabetes epidemic grows (see Figure 1). It is clear that inpatient hyperglycemia is a frequent problem, and as the number of patients with diabetes increases, the occurrence of hyperglycemia due to poorly controlled diabetes is also likely to rise.
Patients with no previous diagnosis of diabetes also comprise a significant proportion of hospitalized patients with hyperglycemia. If 60% to 70% of hospital patients with hyperglycemia have diabetes, at least 30% have no known history of diabetes.[5,10] A study by Umpierrez et al. found that among all patients admitted to a community teaching hospital for whom BG measurements were recorded during the hospital stay, 12% had newly identified hyperglycemia. Moreover, data suggest that hyperglycemia is often untreated in hyperglycemic patients with no history of diabetes.[5,10] These patients subsequently experience poorer health outcomes than normoglycemic patients or patients known to have diabetes. For example, in the study by Umpierrez et al., inpatient mortality was 16% among patients with newly diagnosed hyperglycemia compared with 1.7% for normoglycemic patients and 3.0% for patients with known diabetes (see Figure 2). The length of hospitalization was also significantly longer for patients newly diagnosed with hyperglycemia at 9.0 ± 0.7 days vs 5.5 ± 0.2 days for patients with diabetes (P<.001) and 4.5 ± 0.1 days for normoglycemic patients (P<.001).
Evidence indicates that hyperglycemia in the hospital setting leads to greater risk of adverse health results, including mortality, increased duration of ventilator support, increased length of hospital stay, transfusion, renal failure/dialysis, infection/sepsis, congestive heart failure (CHF), and poor stroke outcome.[2,4,5,13] The effects of high BG on various cells and organ systems are believed to underlie these poor health outcomes. The possible mechanisms linking high BG and poor health outcomes have been reviewed by Clement et al. In the immune system, hyperglycemia decreases phagocyte activity and lymphocyte numbers, resulting in immunosuppression and increased susceptibility to infection. Hyperglycemia has numerous effects on the cardiovascular system. It impairs ischemic preconditioning, thereby increasing cardiovascular susceptibility to ischemic insult. It increases cardiac myocyte death and blood pressure, and it causes electrophysiological changes. Hyperglycemia favors thrombosis by promoting platelet hyperactivity and reducing plasma fibrinolytic activity. It increases production of a number of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). It promotes endothelial cell dysfunction, and it exacerbates ischemic cerebral damage. Treatment of hyperglycemia reverses some of these effects. For example, reducing BG levels has been reported to improve leukocyte function. Therefore, it is not surprising that tight glycemic control has been demonstrated to improve health outcomes for patients in hospital settings.
Glycemic control improves morbidity and mortality for patients who experience inpatient hyperglycemia. As evidence has emerged supporting the relationship between treatment of hyperglycemia and improved health outcomes, guidelines and practice recommendations have been developed.[1,2,3] Guidelines for glycemic control in inpatient settings recommend glycemic targets and techniques to achieve them. A summary of glycemic targets for intensive care unit (ICU) and non-ICU settings is presented in Table 1. These targets are fairly consistent across the 3 guideline documents.
Inpatient Glycemic Targets
||ADA Technical Review
||ACE Position Statement
||ADA Practice Guidelines
|| As close to 110 mg/dL as possible, and generally
||<110 mg/dL preprandial and
<180† mg/dL peak postprandial
|| =110 mg/dL preprandial
and =180 mg/dL maximal
||90-130‡ mg/dL preprandial
and <180 mg/dL postprandial
*4.4-6.1 mmol/L. †10.0 mmol/L. ‡5.0-7.3 mmol/L.
Intravenous (IV) or subcutaneous (SC) insulin administration is currently the best way to achieve good glycemic control in the hospital setting. Oral diabetes agents (eg, sulfonylureas, metformin, thiazolidinediones) are not good candidates for controlling hyperglycemia in the hospital setting because they have limitations for use in some individuals (eg, cardiac patients), and they do not allow for rapid control of BG levels. In addition, data are insufficient to direct use of these agents for glycemic control in the hospital setting. However, insulin use is considered to be a high-risk therapy, particularly because of the possibility of life-threatening hypoglycemia. An understanding of insulin physiology, confidence with dosing, and recognition of the importance of tailored regimens are essential to safe and effective use of insulin in the hospital setting.[3,7] Protocols for implementing insulin therapy and clearly written orders are also important.[2,7] The AACE has developed a slide-based reference resource of several IV insulin protocols.
Insulin may be provided by several techniques in the hospital setting: continuous variable-rate IV insulin drip, basal/bolus therapy via multiple daily injections, premixed insulin, and correction-dose insulin. Intravenous insulin is preferred in some clinical situations including, but not limited to[2,3]:
- Diabetic ketoacidosis and nonketotic hyperosmolar state
- General preoperative, intraoperative, and postoperative care
- Postoperative period following heart surgery
- Organ transplantation
- MI or cardiogenic shock
- Exacerbated hyperglycemia during high-dose glucocorticoid therapy
- NPO status in type 1 diabetes
- Critical illness
- Dose-finding strategy prior to conversion to SC insulin therapy
- Total parenteral nutrition therapy
- Labor and delivery
- Other illnesses requiring prompt glucose control
Regular insulin is most appropriate for IV insulin; data are not sufficient to recommend the use of rapid-acting analogs. Basal/bolus therapy combines long-acting (glargine, Ultralente) or intermediate-acting (NPH or Lente) insulin analogs with rapid-acting (lispro or aspart) insulin analogs or regular insulin. Premixed insulin is appropriate for patients transitioning to outpatient care, and rapid-acting analogs are used for correction dosing.
Another technique for insulin administration that has been used extensively in hospital settings is the sliding-scale approach, in which insulin is administered in response to hyperglycemia and based on BG levels. This strategy should not be confused with correction-dose therapy, which is an adjunct to scheduled insulin. Use of sliding-scale insulin regimens that do not include intermediate-acting insulin is discouraged.[2,3] The sliding-scale approach promotes reaction to, rather than prevention of, hyperglycemia and results in rapid changes in BG levels (see Figure 3). The increased risks of hyperglycemia, hypoglycemia, and iatrogenic ketoacidosis associated with use of the sliding-scale approach are unacceptably high.
At the end of her presentation, Dr Levetan provided the following key reminders:
- Measure BG in all patients admitted with acute illness
- All patients with type 1 diabetes will require at least basal insulin replacement
- Most insulin-treated patients will require continued insulin therapy
- Consider insulin therapy in any patient with random BG >180 mg/dL on a standard medical floor
- The BG goal on a unit is 80-110 mg/dL
- Consider NOT using sliding scales
- American Diabetes Association. Clinical practice recommendations 2006. Diabetes Care. 2006;29:S1-S85.
- American College of Endocrinology. Position statement on inpatient diabetes and metabolic control. Clin Endocrinol. 2004;10:77-82.
- Clement S, Braithwaite S, Magee M, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-591.
- Van Den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359-1367.
- Umpierrez G, Isaacs S, Bazargan N, You X, Thaler L, Kitabchi A. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87:978-982.
- Pittas A, Siegel R, Lau J. Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2004;164:2005-2011.
- American Association of Clinical Endocrinologists, American Diabetes Association. Position statement based on consensus development conference recommendations from, “Inpatient diabetes and glycemic control: a call to action conference.” Available at: http://www.diabetes.org/uedocuments/InpatientDMGlycemic
ControlPositionStatement02.01.06.REV.pdf. Accessed July 13, 2006.
- 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;75:1392-1399.
- Van den Berghe G, Wouters PJ, Keteloot K, Hilleman DE. Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients. Crit Care Med. 2006;34:896-897.
- Levetan C, Passaro M, Jablonski K, Kass M, Ratner R. Unrecognized diabetes among hospitalized patients. Diabetes Care. 1998;21:246-249.
- Metchick LN, Petit WA Jr, Inzucchi SE. Inpatient management of diabetes mellitus. Am J Med. 2002;113:317-323.
- Centers for Disease Control and Prevention National Diabetes Surveillance System. Number (in thousands) of hospital discharges with diabetes as any-listed diagnosis, United States, 1980-2003. Available at: http://www.cdc.gov/diabetes/statistics/dmany/fig1.htm. Accessed July 12, 2006.
- Levetan CS. Effect of hyperglycemia on stroke outcomes. Endocr Pract. 2004;10(suppl 2):34-39.
- American Association of Clinical Endocrinologists. Strategies and protocols for achieving inpatient glycemic control. Available at: http://www.aace.com/meetings/consensus/icc/F.ppt. Accessed July 16, 2006.