Diabetes Care, Vol 21, Issue 3 403-408, Copyright © 1998 by American Diabetes Association

ARTICLES

Longitudinal changes in pancreatic beta-cell function and metabolic clearance rate of insulin in pregnant women with normal and abnormal glucose tolerance

PM Catalano, NM Drago and SB Amini
Department of Reproductive Biology, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH 44109, USA. pcatalano@metrohealth.org

OBJECTIVE: To evaluate basal pancreatic beta-cell secretion and suppression during infused insulin and the metabolic clearance rate of insulin in women with normal and abnormal glucose tolerance prior to conception and during pregnancy. RESEARCH DESIGN AND METHODS: Seven women with normal glucose tolerance and nine women with abnormal glucose tolerance during gestation were evaluated prior to conception, in early (12-14 weeks) and late (34-36 weeks) gestation. Basal insulin and C-peptide were measured after an 11-h fast and during the last 40 min of a 2-h hyperinsulinemic-euglycemic clamp at 40 mU.m-2.m-1. Suppression of basal C-peptide was calculated as the steady-state C-peptide/basal C-peptide. The metabolic clearance rate of insulin was calculated by dividing the insulin infusion rate by the steady-state insulin concentration, which was corrected for residual beta-cell secretion. RESULTS: No significant differences were noted in the following parameters between women with normal and abnormal glucose tolerance with advancing gestation: increase in basal insulin (P = 0.20) and C-peptide (P = 0.12), ability of infused insulin to decrease basal C-peptide concentration (P = 0.22), and metabolic clearance rate of insulin (P = 0.76). There was a significant 65% increase in both basal insulin (P = 0.0005) and C-peptide (P = 0.0002) concentrations in all subjects with advancing gestation. There was a significant (P = 0.0001) decrease in the ability of the infused insulin to decrease basal C-peptide concentration. C-peptide as a percentage of the basal was 64% before conception, 74% in early pregnancy, and 108% in late pregnancy. The metabolic clearance rate of insulin significantly (P = 0.0005) increased with advancing gestation: pregravid 442 ml.m-2.min-1, early pregnancy 514 ml.m-2. min-1, and 526 ml.m-2.min-1 in late pregnancy. CONCLUSIONS: Pregnancy is accompanied by progressive alterations in insulin kinetics, which are partly responsible for the hyperinsulinemia of this condition. These alterations are more likely a homeostatic response to the increased physiological insulin resistance of pregnancy.
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