On diabetes: insulin resistance impairment was found to be due primarily to a defect in nonoxidative glucose disposal, rather than to a defect in glucose oxidation. First-and second-phase insulin secretion were also increased in the offspring, suggesting compensatory hypersecretion of insulin in response to insulin resistance in these individuals. Major reductions in nonoxidative glucose disposal with only modest reductions in glucose oxidation have also been observed in Caucasian nondiabetic firstdegree relatives of diabetic subjects (6). Family clustering of insulin resistance measurements offers another method of demonstrating the effects of genes on these phenotypes. Such clustering has been demonstrated in Pima Indians, using the euglycemic hyperinsulinemic clamp technique (7), and in Caucasians, using the FSIVGTT (8). The range of insulin resistance values found within families was considerably narrower than the range of values across families, indicating that family members are more likely to resemble one another in their degree of insulin resistance than they are to resemble unrelated individuals. Finally, a number of studies have estimated the heritability of insulin resistance. Heritability is defined as the proportion of variance in a trait attributable to the additive effect of genes. Heritability of insulin resistance as estimated from twin studies ranges from 47 to 66%(2). Heritability of fasting insulin and insulin concentration 2 hours after an oral glucose load have also been estimated in a study of extended pedigrees and have been found to be 35% and 13%, respectively (9).