Insulin Secretion in Normal Glucose-Tolerant Relatives of Type 2 Diabetic Subjects: Assessments using hyperglycemic glucose clamps and oral glucose tolerance tests

Abstract

OBJECTIVE To assess insulin secretion in normal glucose-tolerant Caucasian first-degree relatives of type 2 diabetes subjects and in matched normal glucose-tolerant control subjects and to compare insulin secretion as assessed using a hyperglycemic glucose clamp with insulin secretion as assessed using an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS Twenty-one first-degree relatives of type 2 diabetic subjects and 21 control subjects without a family history of type 2 diabetes, who were matched for sex, age, BM1, waist-to-hip ratio, and aerobic capacity, underwent a hyperglycemic glucose clamp (10 mmol/1, 180 min). An OGTT (75 g glucose in 300 ml water) was also performed. RESULTS First-phase insulin release (plasma insulin, 0–10 min) was 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 showed decreased plasma insulin levels from 120 min onward (all P < 0.05), decreasing to geometric mean (95% CI) levels of 330 (270–402) and 462 (366–582) pmol/1 at 180 min in relatives and control subjects, respectively. The insulin sensitivity index (ISI) as assessed using a hyperglycemic clamp was not different between the two groups. Mean ± SE ISI during the 3rd hour was 27.5 ± 2.2 and 30.5 ± 3.0 μg · kg−1 · min−1 · pmol−1 · l−1 in relatives and control subjects, respectively (P > 0.20). At 90 min after the OGTT, log plasma insulin levels correlated significantly with secondphase 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 release, compared with matched control subjects. After an OGTT, 90-min values of log plasma insulin and 90-min values of the ratio of log plasma insulin to blood glucose may be good indicators of insulin secretory properties in normal glucose-tolerant family members of type 2 diabetic subjects.