Hyperinsulinemia in Nondiabetic Asian Subjects Using Specific Assays for Insulin, Intact Proinsulin, and Des-31, 32-Proinsulin

Abstract

OBJECTIVE To investigate the contributions of intact proinsulin and of des-31,32-proinsulin to fasting concentrations of insulin-like molecules in nondiabetic subjects from two ethnic groups (Asian and white) and to see whether Asian subjects are hyperinsulinemic compared with white subjects using highly specific assays for insulin. RESEARCH DESIGN AND METHODS We investigated subjects with normal glucose tolerance (NGT) (82 Asian and 67 white) and impaired glucose tolerance (IGT) (16 Asian and 13 white), diagnosed by using standard World Health Organization criteria. Highly specific monoclonal antibody-based assays were used to measure insulin, intact proinsulin, and des-31, 32-proinsulin. An index of insulin secretion was derived as a ratio of incremental insulin to incremental glucose concentrations from 0 to 30 min during an oral glucose tolerance test. RESULTS Asian subjects with NGT, despite being significantly thinner than whites (BMI 24.4 ± 3.5 vs. 25.7 ± 3.7 kg/m2, P = 0.04), had a more central distribution of obesity (subscapsular-to-triceps skinfold ratios 1.36 ± 0.69 vs. 1.17 ± 0.41, P = 0.047). Asian subjects with NGT showed significant hyperinsulinemia 2 h after oral glucose load (plasma insulin median 274 pmol/l [range 26–1,505] vs. 186 pmol/l [27–720], P < 0.005) compared with whites. Asian subjects with NGT also had significantly higher insulin increments (P < 0.02) compared with white subjects and significantly higher fasting concentrations of intact proinsulin (median 2.7 pmol/l [range 0.9–14.1] vs. 2.1 [0.8-7.9], P < 0.02) but not of des-31, 32-proinsulin. The ratio of proinsulin-like molecules to the total sum of three insulin-like molecules, however, was similar between Asian and white subjects with NGT and IGT. CONCLUSIONS These results indicate that when specific assays for insulin are used, Asian subjects show postglucose load hyperinsulinemia and fasting hyperproinsulinemia compared with white subjects, suggesting increased insulin secretion and/or the presence of underlying insulin resistance in this ethnic group. The contribution of proinsulin-like molecules to total insulin-like molecules was similar between Asian and white subjects with NGT and IGT, and there was no contribution to hyperinsulinemia in Asian subjects.