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 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).


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, BMI, waist-to-hip ratio, and aerobic capacity, underwent a hyperglycemic glucose clamp (10 mmol/l, 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/l 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 micrograms.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 second-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 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.
van Haeften
T W
TW
Department of Internal Medicine, Utrecht University, The Netherlands. t.w.vanhaeften@digd.azu.nl
Dubbeldam
S
S
Zonderland
M L
ML
Erkelens
D W
DW
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005192:Family Health; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose