INSULIN-SECRETION, INSULIN ACTION, AND HEPATIC GLUCOSE-PRODUCTION IN IDENTICAL-TWINS DISCORDANT FOR NON-INSULIN-DEPENDENT DIABETES-MELLITUS

12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insu lin clamp, 40 mU/m(2) per min), hepatic glucose production (HGP, [3-H- 3]glucose infusion), and insulin secretion (oral glucose tolerance tes t and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired gluco se tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twin s were insulin resistant and had a delayed insulin and C-peptide respo nse during oral glucose tolerance tests compared with controls. Furthe rmore, the nondiabetic twins had a decreased first-phase insulin respo nse and a decreased maximal insulin secretion capacity during hypergly cemic clamping and intravenous glucagon administration. Nondiabetic tw ins and controls had similar rates of HGP. Compared with both nondiabe tic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired i nsulin secretion pattern as determined by all tests. In conclusion, de fects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDD M susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM.