The Use of U-500 in Patients With Extreme Insulin Resistance

The Diabetes Control and Complication Trial (1) and the U.K. Prospective Diabetes Study (2,3), as well as other smaller trials (4), have established the benefit of treating type 1 and type 2 diabetes to levels of glycemia as close to normal as possible. These studies have formed the basis for the therapeutic targets set forth in the most recent American Diabetes Association (ADA) guidelines (5). There is a subset of patients classified by the ADA as having “other specific types of diabetes”; this group represents a major therapeutic challenge in terms of achieving glycemic goals (6). These patients have more extreme forms of insulin resistance than typical type 2 diabetic patients, and many manifest various syndromic classifications (Fig. 1). Furthermore, for the purpose of this discussion, we are including patients with extreme endogenous hyperinsulinemia or hyperglycemic patients who require doses of exogenous insulin of >200 units/day or in pediatric patients doses >3 units · kg−1 · day−1. This includes a subset of obese type 2 diabetic patients. Extreme forms of insulin resistance may also occur as a temporary state with pregnancy, with endocrinopathies and under various other stress conditions such as an infection, or with exogenous steroid use (Fig. 2). The practical issue of insulin management is essentially the same for all of these various patient categories. While we have defined the more extreme forms of insulin resistance whose requirements are >200 units insulin/day, this is clearly an arbitrary definition. Currently glycemic goals for both type 2 diabetes and “the other specific types of diabetes” are generally not being met. Part of the reason for this is that patients clearly are on insufficient doses of insulin. For instance, the median dose of insulin in a group of Pima Indians under treatment is 70 units/day …