1. Regular insulin—Regular insulin is a short-acting, soluble crystalline zinc insulin whose hypoglycemic effect appears within 30 minutes after subcutaneous injection, peaks at about 2 hours, and lasts for 5–7 hours when usual quantities (ie, 5–15 U) are administered. For very insulin-resistant subjects who would otherwise require large volumes of insulin solution, a U500 preparation of human regular insulin is available both in a vial form and a disposable pen. If the vial form is used, it is necessary to use a U100-insulin syringe or tuberculin syringe to measure doses.
TABLE 41–5 Summary of bioavailability characteristics of the insulins.
TABLE 41–6 Some insulin preparations available in the United States.1
All insulins are now made by recombinant technology; they should be refrigerated and brought to room temperature just before injection. NPA, neutral protamine aspart; NPL, neutral protamine lispro.
The physician should then carefully note dosages in both units and volume to avoid overdosage. The disposable pen avoids this conversion issue and dispenses the regular U500 insulin in 5-unit increments.
Intravenous infusions of regular insulin are particularly useful in the treatment of diabetic ketoacidosis and during the perioperative management of insulin-requiring diabetics.
2. Rapidly acting insulin analogs—Insulin lispro (Humalog) is an insulin analog in which the proline at position B28 is reversed with the lysine at B29. Insulin aspart (Novolog) is a single substitution of proline by aspartic acid at position B28. Insulin glulisine (Apidra) differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 by glutamic acid. When injected subcutaneously, these three analogs quickly dissociate into monomers and are absorbed very rapidly, reaching peak serum values in as little as 1 hour. The amino acid changes in these analogs do not interfere with their binding to the insulin receptor, with the circulating half-life, or with their immunogenicity, which are all identical to those of human regular insulin.
Clinical trials have demonstrated that the optimal times of preprandial subcutaneous injection of comparable doses of the rapid-acting insulin analogs and of regular human insulin are 15 minutes and 45 minutes before the meal, respectively. Although the more rapid onset of action has been welcomed as a great convenience by patients with diabetes who object to waiting as long as 45 minutes after injecting regular human insulin before they can begin their meal, patients must be taught to ingest adequate absorbable carbohydrate early in the meal to avoid hypoglycemia during the meal. The analogs also have lowest variability of absorption: approximately 5%. This compares with 25% for regular insulin. Another desirable feature of rapidly acting insulin analogs is that their duration of action remains at about 4 hours for most commonly used dosages. This contrasts with regular insulin, whose duration of action is significantly prolonged when larger doses are used.
The rapidly acting analogs are commonly used in insulin pumps. In a double-blind crossover study comparing insulin lispro with regular insulin in insulin pumps, persons using insulin lispro had lower HbA1c values and improved postprandial glucose control with the same frequency of hypoglycemia. However, the concern remains that in the event of pump failure, users of the rapidly acting insulin analogs will have more rapid onset of hyperglycemia and ketosis.