Delayed Response to U-500 Regular Insulin.

Abstract

Severe insulin resistance was defined 45 years ago as a daily insulin requirement of >200 units (1) and, more recently, as an insulin requirement >2 units/kg/day (2). Because severely insulin-resistant patients require large amounts of insulin, the corresponding injection volume of traditional U-100 insulin is also large. In addition to the inconvenience to patients of having to take an increased number of injections, insulin absorption from large injectate volumes is impaired (3–5). For these reasons, increasing numbers of severely insulin-resistant patients, whose insulin resistance is most often due to obesity, are being treated with U-500 regular insulin (6). The pharmacokinetic (PK) and pharmacodynamic (PD) properties of U-500 regular insulin more closely resemble those of NPH insulin than of U-100 regular insulin (2,7). Therefore, we adjust the doses of U-500 regular insulin using the same principles as are used for NPH insulin given before breakfast and supper, only with greater dose changes. Our algorithm for using U-500 regular insulin is shown in Figure 1. Not shown in the figure is the situation in which the prebreakfast and presupper glucose levels meet target values but A1C levels are still above target. In that case, patients are asked to measure their blood glucose levels before lunch and before their bedtime snack, and short- or rapid-acting insulin is added in separate injections if those glucose values are high. FIGURE 1. Algorithm for starting and adjusting U-500 regular insulin doses. Unexplained hypoglycemia includes episodes that are not explained by delayed, smaller than usual, or missed meals; increased exercise; or having taken an incorrect insulin dose. BG, blood glucose; TDD, total daily dose. Reprinted with permission from Diabetes Care …