Inpatient hyperglycemia management: A practical review for primary medical and surgical teams
ABSTRACTInpatient hyperglycemia is common and is associated with an increased risk of hospital complications, higher healthcare resource utilization, and higher in-hospital mortality rates. Appropriate glycemic control strategies can reduce these risks, although hypoglycemia is a concern. In critically ill patients, intravenous (IV) insulin is most appropriate, with a starting threshold no higher than 180 mg/dL. Once IV insulin is started, the glucose level should be maintained between 140 and 180 mg/dL. In noncritically ill patients, basal-bolus regimens with basal, prandial, and correction components are preferred for those with good nutritional intake. In contrast, a single dose of long-acting insulin plus correction insulin is preferred for patients with poor or no oral intake. Measuring hemoglobin A1c at admission is important to assess glycemic control and to tailor the treatment regimen at discharge.
KEY POINTS
- Hyperglycemia in hospitalized patients, with or without diabetes, is associated with adverse outcomes.
- Measurement of hemoglobin A1c is recommended in all patients at hospital admission.
- Insulin administration is the preferred way to control hyperglycemia in hospitalized patients, with a starting threshold below 180 mg/dL then maintaining a level between 140 and 180 mg/dL.
INPATIENT MANAGEMENT OF HYPERGLYCEMIA AND DIABETES
Insulin regimens in critical care settings
Insulin administration is the preferred way to control hyperglycemia in hospitalized patients. In critically ill patients, such as those with hypotension requiring pressor support, hyperglycemic crises, sepsis, or shock, insulin is best given via continuous intravenous (IV) infusion. The short half-life of IV insulin (< 15 minutes) allows flexibility in adjusting the infusion rate in the event of unpredicted changes in nutrition or the patient’s health. If the glucose level rises above 180 mg/dL, IV insulin infusion should be started to maintain levels below 180 mg/dL.13,26,28,29
A variety of infusion protocols have been shown to be effective in achieving glycemic control with a low rate of hypoglycemia. The ideal protocol should allow flexible rate adjustment taking into account current and previous glucose values as well as changes in infusion rate. Hourly glucose measurements until stable glycemic control is established, followed by point-of-care testing every 1 to 2 hours, is needed to assess response to therapy and prevent hypoglycemia.
,Insulin regimens in noncritical care settings
For most patients in a general, non-ICU setting, SC insulin therapy with basal insulin administered once or twice daily, alone or in combination with prandial insulin, is effective and safe.13 Inhaled insulin is approved by the US Food and Drug Administration, but its use in the hospital has not been studied. The use of sliding-scale insulin is not acceptable as the single regimen in patients with diabetes, as it results in undesirable hypoglycemia and hyperglycemia.30Figure 1 presents an algorithm for selecting initial insulin treatment for patients with type 2 diabetes in the non-ICU setting.
Basal insulin prevents hyperglycemia during fasting states. Basal insulin is usually given as a once- or twice-daily long-acting insulin, such as glargine and detemir insulin. On occasion, twice-daily intermediate-acting insulin (neutral protamine Hagedorn; NPH) is used as a basal insulin.
Prandial insulin, also referred to as nutritional or bolus insulin, is given before meals as rapid-acting insulin (aspart, lispro, or glulisine) or short-acting insulin (regular) to prevent postmeal hyperglycemia. Rapid-acting insulin is preferred to regular insulin because of the faster onset and shorter duration of action, which may reduce the risk of hypoglycemia.
Correction or supplemental insulin is given to correct hyperglycemia when the glucose is above the goal. The same formulation is given together with prandial insulin.
Total daily dose of insulin is a measure that comprises basal and prandial insulin Figure 1 lists the recommended total daily dose for different clinical situations and patient populations.
Basal-bolus insulin usually refers to a regimen of long-acting basal insulin plus prandial insulin. In patients with adequate oral intake, the basal-bolus approach is preferred. The RABBIT 2 trial reported that basal-bolus regimens resulted in greater improvement in glucose control than sliding-scale regimens (correction insulin alone without basal or prandial components) in general medicine patients with type 2 diabetes.32 In general surgery patients, basal-bolus regimens significantly improved glucose control and reduced the numbers of postoperative complications, primarily wound infections compared with sliding-scale regimens.4
Multiple doses of NPH and regular insulin were compared with basal-bolus treatment with long-acting and rapid-acting insulin in two controlled trials in medical patients with type 2 diabetes.20,33 Both studies reported that treatment with NPH and regular insulin resulted in similar improvements in glycemic control and no difference in the rate of hypoglycemic events or in hospital length of stay, compared with basal-bolus insulin. Because NPH has a peak of action approximately 8 to 12 hours after injection, there is a risk of hypoglycemia in patients with poor oral intake.
In hospitalized patients who have reduced total caloric intake due to lack of appetite, acute illness, medical procedures, or surgical interventions, the Basal Plus trial34 reported that a single daily dose of glargine plus correction doses of rapid-acting insulin resulted in similar improvement in glycemic control and no difference in the frequency of hypoglycemia compared with a standard basal-bolus regimen. These results indicate that the basal-plus-correction regimen may be preferred for patients with poor or no oral intake, whereas an insulin regimen with basal, nutritional (basal-bolus), and correction components is preferred for patients with good nutritional intake.35
SC insulin dosing refers to insulin doses administered subcutaneously calculated based either on weight or on home insulin doses. For insulin-naive patients, the starting total daily dose of insulin can usually be computed as 0.4 to 0.5 U/kg/day. Higher starting doses are associated with greater odds of hypoglycemia than doses lower than 0.2 U/kg/day.36 In elderly patients and those with impaired renal function, lower initial daily doses (≤ 0.3 U/kg) may reduce the risk of hypoglycemia.26
In patients treated with insulin prior to admission, the total daily insulin dose at home can be given as half long-acting basal insulin and half prandial insulin. The dose can be reduced by 20% to 25% to prevent hypoglycemia, particularly in those with poor or uncertain caloric intake.31
Noninsulin therapies
The use of oral antidiabetic agents is generally not recommended in hospitalized patients due to the limited data available on their safety and efficacy, frequent contraindications, risk of hypoglycemia, and slow onset of action that may preclude achieving rapid glycemic control and daily dose adjustments. Table 3 lists the pros and cons of these agents in hospitalized patients.
The safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the management of inpatient hyperglycemia was evaluated in a randomized pilot study in patients with type 2 diabetes treated at home with diet, oral antidiabetic agents, or a low daily insulin dose (≤ 0.4 U/kg/day).37 Patients were randomized to one of two treatments:
- Sitagliptin alone or with low-dose glargine insulin
- Basal-bolus insulin regimen plus supplemental doses of insulin lispro.
Both treatment regimens resulted in similar improvement in mean daily glucose concentrations. However, patients admitted to the hospital with glucose levels above 180 mg/dL in the sitagliptin group had higher mean daily glucose levels than patients treated with basal-bolus or sitagliptin plus glargine.
Transitioning from IV to SC insulin
When patients in critical care units are ready to be transferred to a general medical floor, appropriate transition from IV insulin to scheduled SC insulin is needed to prevent rebound hyperglycemia. This is imperative in patients with type 1 diabetes in whom just a few hours without insulin can result in diabetic ketoacidosis.
There are three general ways to calculate the SC insulin dose during the transition period. The first two methods are weight-based and based on the home dose, as previously discussed. The third method is to extrapolate from the IV insulin. A common way is to sum up the total IV insulin dose in the past 6 or 8 hours and multiply by 3 or 4, and then reduce by 20% to achieve the basal insulin dose, presuming the patient had no oral intake on the IV insulin infusion. This last method is preferred in hemodynamically stable patients with stable insulin requirements.
If long-acting insulin is chosen as basal insulin, it should be given 2 to 4 hours before discontinuation of the IV insulin infusion. Intermediate-acting insulin should be given 1 to 2 hours before IV insulin discontinuation.
