ALTERED C-PEPTIDE INSULIN MOLAR RATIOS AND GLUCOSE-TURNOVER RATES AFTER STIMULATION IN NONDIABETIC OFFSPRINGS OF TYPE-II DIABETIC-PATIENTS

We evaluted the serum glucose/insulin/C-peptide dynamics and C-peptide/insulin molar ratios during sequential standard meal and intravenous (IV) glucagon testing for 240 minutes in eight genetically predisposed but nondiabetic female offsprings of type II diabetic patients and seven weight-matched, normal female controls. Glucose turnover rates and metabolic clearance rates of glucose (MCRG) were also determined isotopically by the D-[3-3H]glucose infusion technique. All the subjects had normal fasting serum glucose and glycosylated hemoglobin (HbA1) values. After meal ingestion, mean serum glucose concentrations were not different except for 120 to 180 minute values, which were significantly higher in the offsprings v controls. After intravenous glucagon infusion, percent maximum increments of glucose were no different. Mean basal immunoreactive insulin (IRI) levels were significantly (P < 0.02) higher in the nondiabetic offsprings v controls. Following meal ingestion, mean IRI rose to a peak at 40 minutes in both groups, but values were significantly (P < 0.001) higher in the offsprings v controls. After glucagon administration, the percent maximum increment was significantly (P < 0.05) lower in the offsprings v controls. Despite exaggerated IRI levels in the offsprings, the mean fasting and stimulated C-peptide levels were identical in both groups throughout the study period. Basal and stimulated C-peptide/IRI molar ratios were quantitatively lower but qualitatively no different in the nondiabetic offsprings v controls throughout the study period. Mean basal hepatic glucose output (HGO) was higher but not statistically different in the offsprings compared with the controls (2.10 .+-. 0.28 v 1.65 .+-. 0.15 mg/kg .cntdot. min). Following meal ingestion, the splanchnic glucose output (RA) increased significantly at t = 20, 100, 120, 140, and 180 minutes in the offsprings v controls. The basal MCRG was not significantly different in the offsprings v controls (83 .+-. 10 v 75 .+-. 6 mL/m2 .cntdot. min). After meal ingestion, MCRG values were significantly higher at t = 20, 40, 60, 80, and 100 minutes in the offsprings v controls. Thus, our data indicates that decreased C-peptide/insulin molar ratios, which may partly reflect hepatic insulin extraction, and altered glucose fluxes may exist in healthy female offspring of noninsulin-dependent diabetic patients.