β- and α-Cell Dysfunction in Subjects Developing Impaired Glucose Tolerance. Outcome of a 12 Year Prospective Study in Postmenopausal Caucasian Women

Abstract

OBJECTIVE: This study assessed insulin and glucagon secretion in relation to insulin sensitivity in Caucasian women who develop impaired glucose tolerance (IGT) versus those who maintain normal glucose tolerance (NGT) over a 12 year period.

RESEARCH DESIGN AND METHODS: At baseline and after three, eight and twelve years, glucose tolerance (75 g OGTT), insulin sensitivity (euglycemic, hyperinsulinemic clamp) and insulin and glucagon secretion (2 to 5-min responses to 5g arginine iv at fasting, 14 and >25 mmol/l glucose) were determined in 53 healthy Caucasian women (58 years at baseline) whom all had NGT at baseline.

RESULTS: During the twelve year period, 26 subjects developed IGT whereas the remaining 27 subjects maintained NGT throughout the twelve-year period. Subjects developing IGT had lower insulin sensitivity than those maintaining NGT in the tests preceding diagnosis of IGT (P<0.05 or less). When judged in relation to insulin sensitivity, ß-cell glucose sensitivity and maximal insulin secretion were lower in those who later developed IGT than in those maintaining NGT at all tests (P<0.05 or less). Furthermore, subjects who developed IGT had defective suppression of glucagon secretion by glucose in the test preceding diagnosis of IGT when they still had NGT (P<0.05 or less).

CONCLUSION: ß- and α-cell dysfunction are evident several years before diagnosis of IGT, and islet dysfunction is manifested as impaired glucose sensitivity of the ß- and α-cells and reduced maximal insulin secretion.