The majority of hospital patients are admitted to general medical and surgical wards rather than intensive care units (ICUs). Inpatient hyperglycemia is also common on the general wards, although blood glucose (BG) levels for hyperglycemic patients on medical and surgical floors tend to be in the range of 175 mg/dL, not 200 to 300 mg/dL. This is true in patients with known diabetes as well as in patients with newly recognized hyperglycemia. The belief that these BG levels are not dangerously high may contribute to the lack of treatment for hyperglycemia, especially in patients with no previous diagnosis of diabetes. One study demonstrated that patients with no previous diagnosis of diabetes were less likely to receive treatment for hyperglycemia than patients with diabetes. This finding is troublesome, as hyperglycemia is associated with increased mortality among non-ICU patients (see Figure 1).
Although there is extensive literature regarding the relationship between hyperglycemia and poor outcomes among critically ill patients, there is relatively little information regarding the same relationship for non-ICU patients. One of the few papers in this area is an observational study that describes a 2.7-fold increase in the risk of infection and a 5.7-fold increase in serious infection among surgery patients with BG levels >220 mg/dL. In general, studies of clinical outcomes for surgery patients with diabetes have revealed that hyperglycemia is associated with greater infection rate, impaired wound healing, increased length of stay, higher operative morbidity, and higher hospital mortality. The deleterious effects of hyperglycemia are not limited to surgical patients in non-ICU settings. For example, a study of patients with community-acquired pneumonia indicated that elevated BG on admission was associated with increased mortality and complications (see Figure 2).
As another example, patients in non-ICU settings may require total parenteral nutrition (TPN), predisposing them to hyperglycemia. A recent study supports tight glycemic control among patients receiving TPN, as hyperglycemia in these patients is associated with increased mortality, infection, renal failure, and cardiac complications (see Figure 3).
There is sufficient evidence supporting the maintenance of tight glycemic control in non-ICU settings, and target BG levels for patients in non-ICU settings have been proposed (see Table 1), but barriers to the improvement of glycemic control on general medical and surgical wards still exist. One obstacle is the lack of prospective, randomized, interventional studies to demonstrate the benefits of tight glycemic control on general medical and surgical wards and provide guidance for the development of practice protocols. Fear of hypoglycemia is also a substantial barrier to tight glucose control and actually leads to poor clinical actions such as holding a patient’s diabetic regimen, initiation of sliding-scale insulin coverage, and delayed initiation of basal/bolus insulin therapy. “Clinical inertia” is yet another stumbling block and is exemplified in the persistent use of ineffective strategies, such as sliding-scale insulin therapy, and lack of treatment adjustment for patients who experience hyperglycemia or hypoglycemia.[7,8]
Table 1. Blood Glucose Targets for Non-ICU Settings
| ADA Technical Review
||ACE Position Statement
<110* mg/dL preprandial
<180† mg/dL peak postprandial
≤110 mg/dL preprandial
≤180 mg/dL maximal
90-130‡ mg/dL preprandial
<180 mg/dL postprandial
*6.1 mmol/L. †10.0 mmol/L. ‡5.0-7.3 mmol/L.
For patients who are not critically ill, therapy options for maintaining glycemic control include continuous variable-rate intravenous (IV) insulin drip, basal/bolus therapy via multiple daily injections, premixed insulin, sliding-scale administration of short-acting insulin, and oral agents. The sliding-scale approach as a stand-alone regimen is not recommended, as it increases the risk of both hyperglycemia and hypoglycemia. One study demonstrated that use of a sliding-scale protocol increased the relative risk of hyperglycemia approximately 3-fold over no treatment. A 2005 study by Ku et al. demonstrated that implementation of an insulin infusion protocol in non-ICU settings resulted in lower rates of hypoglycemia (BG = 60 mg/dL) and hyperglycemia (BG ≥180 mg/dL). For basal/bolus therapy, combinations of different types of insulin, such as NPH and regular insulin or long-acting and rapid-acting insulin, are administered in multiple injections. The combination of NPH and regular insulin is commonly used by patients but may not be well-suited to inpatient settings because it lacks the flexibility to fit the potentially irregular meal schedule a patient may encounter in the hospital. A combination of long-acting insulin (eg, glargine or detemir) plus a rapid-acting insulin (eg, lispro, aspart, or glulisine) is commonly used for patients in the hospital because it allows for more rapid dosing adjustments (see Figure 4). Practical recommendations for perioperative glucose control are described in detail in a recently published review.
Based on his personal experience, Dr Umpierrez provided recommendations for basal/bolus insulin therapy in noncritically ill patients. In his practice, Dr Umpierrez discontinues oral antidiabetic agents on admission. The starting total daily dose (TDD) of insulin is estimated using the following calculations:
0.4 U/kg/d x BG between 140 and 200 mg/dL
0.6 U/kg/d x BG between 201 and 400 mg/dL
Half of the TDD is given as insulin glargine and half as a rapid-acting insulin (lispro, aspart, or glulisine). Insulin glargine is delivered once daily at the same time of day, and the rapid-acting insulin is divided equally into 3 doses. If a patient experiences hyperglycemia (FPG >140 mg/dL) without hypoglycemia, the glargine dose is increased by 20%. If the patient experiences hypoglycemia (BG <60 mg/dL), the glargine dose is decreased by 20%.
Dr Umpierrez also highlighted practical guidelines from a recent ADA Technical Review for hospital use of insulin under specific circumstances. Insulin administration is described in terms of programmed (basal and nutritional/mealtime) and supplemental/correction doses. For patients who are eating, basal insulin can be supplied as an intermediate-acting insulin administered twice daily or at bedtime; a long-acting insulin provided once, at the same time, each day; or an insulin drip. Mealtime insulin, in the form of regular or rapid-acting insulin, should be provided 30 to 45 (regular) or 0 to 15 (rapid-acting) minutes before breakfast and dinner. Alternatively, mealtime insulin can be provided at breakfast, lunch, and dinner. Regular and rapid-acting insulin should be avoided at bedtime to minimize nighttime hypoglycemia. For patients who are not eating, the basal regimen is the same as for patients who are eating. No nutritional doses are required, but supplemental/correction doses should be provided every 4 to 6 hours for regular insulin and every 4 hours for rapid-acting insulin. For patients on high-dose glucocorticoid therapy, particular attention is paid to nutritional doses because of the marked elevation in postprandial glucose associated with steroid treatment. Analog mixes may also be used for programmed insulin doses. Patients on high-dose glucocorticoid therapy also have a decreased sensitivity to exogenous insulin.
Dr Umpierrez closed with a reminder that the inpatient setting provides a good opportunity for patient education. While patients are receiving inpatient care to maintain good glycemic control, they may be more aware of the consequences of poor control and may be more receptive to information regarding insulin administration, BG monitoring, treatment of hypoglycemia, meal planning, sick day management, and accessing diabetes education as an outpatient.
- 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.
- Pomposelli JJ, Baxter JK, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenter Enteral Nutr. 1998;22:77-81.
- American College of Endocrinology. Position statement on inpatient diabetes and Metabolic Control. Clin Endocrinol. 2004;10:77-82.
- McAlister FA, Majumdar SR, Blitz S, Rowe BH, Romney J, Marrie TJ. The relation between hyperglycemia and outcomes in 2471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care. 2005;28:810-815.
- Cheung NW, Napier B, Zaccaria C, Fletcher JP. Hyperglycemia is associated with adverse outcomes in patients receiving total parenteral nutrition. Diabetes Care. 28;10:2367-2371.
- Clement S, Braithwaite S, Magee M, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-591.
- Schnipper JL, Barsky EE, Shaykevich S, Fitzmaurice G, Pendergrass ML. Inpatient management of diabetes and hyperglycemia among general medicine patients at a large teaching hospital. J Hosp Med. 2006;1:145-150.
- Knecht LAD, Gauthier SM, Castro JC, et al. Diabetes care in the hospital: is there clinical inertia? J Hosp Med. 2006;1:151-160.
- Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med. 1997;157:545-552.
- Ku SY, Sayre CA, Hirsch IB, Kelly JL. New insulin infusion protocol improves blood glucose control in hospitalized patients without increasing hypoglycemia. Jt Comm J Qual Patient Saf. 2005;31:141-147.
- Smiley DD, Umpierrez GE. Perioperative glucose control in the diabetic or nondiabetic patient. South Med J. 2006;99:580-589.