Genetics of Insulin Resistance

Insulin-stimulated glucose uptake varies widely between individuals. The wide range of variability has been documented by Hollenbeck and Reaven (1) who measured in vivo insulin sensitivity, using the euglycemic clamp technique, in a group of apparently healthy, non-obese subjects with normal glucose tolerance. After dividing the subjects into four quartiles based on their insulin sensitivity values, these investigators observed a two-and-a-half-fold difference in mean insulin sensitivity between subjects in the most sensitive compared to the least sensitive quartile. In fact, the degree of insulin resistance observed in normal individuals can equal that seen in diabetic individuals (1). Thus, although it is now widely appreciated that insulin resistance precedes the development of Type 2 diabetes, it is equally important to recognize that mild or even severe insulin resistance may be found in individuals who will never develop diabetes. There is a substantial body of evidence that points to genetic factors as the source of much of this normal variation in insulin resistance.