INSULIN-SECRETION IN NORMAL GLUCOSE-TOLERANT RELATIVES OF TYPE-2 DIABETIC SUBJECTS - ASSESSMENTS USING HYPERGLYCEMIC GLUCOSE CLAMPS AND ORAL GLUCOSE-TOLERANCE TESTS

OBJECTIVE - To assess insulin secretion in normal glucose-tolerant Cau casian first-degree relatives of type 2 diabetes subjects and in match ed normal glucose-tolerant control subjects and to compare insulin sec retion as assessed using a hyperglycemic glucose clamp with insulin se cretion as assessed using an oral glucose tolerance test (OGTT). RESEA RCH DESIGN AND METHODS - Twenty-one first-degree relatives of type 2 d iabetic subjects and 21 control subjects without a family history of t ype 2 diabetes, who were marched for sex, age, BMI, waist-to-hip ratio , and aerobic capacity underwent a hyperglycemic glucose clamp (10 mmo l/l, 180 min). An OGTT (75 g glucose in 300 mi water) was also perform ed. RESULTS - First-phase insulin release (plasma insulin, 0-10 min) w as not different (multiple analysis of variance [MANOVA]: F = 2.63, P = 0.11). Second-phase insulin release was lower (MANOVA: F = 4.18, P = 0.047). Separate analyses of variance show ed decreased plasma insuli n levels from 120 min onward (all P < 0.05), decreasing to geometric m ean (95% CI) levels of 330 (270-402) and 462 (366-582) pmol/l at 180 m in in relatives and control subjects, respectively. The insulin sensit ivity index (ISI) as assessed using a hyperglycemic clamp was not diff erent between the two groups. Mean +/- SE ISI during the 3rd hour was 27.5 +/- 2.2 and 30.5 +/- 3.0 mu g.kg(-1).min(-1).pmol(-1).1(-1) in re latives and control subjects, respectively (P > 0.20). At 90 min after the OGTT, log plasma insulin levels correlated significantly with sec ond-phase insulin release as assessed using the hyperglycemic glucose clamp. CONCLUSIONS - Normal glucose-tolerant first-degree relatives of type 2 diabetic subjects have a decreased second-phase insulin releas e, compared with matched control subjects. After an OGTT, 90-min value s of log plasma insulin and 90-min values of the ratio of log plasma i nsulin to blood glucose may be good indicators of insulin secretory pr operties in normal glucose-tolerant family members of type 2 diabetic subjects.