Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus

We have determined prehepatic insulin secretion rates (ISRs) in seven patie nts with gestational diabetes mellitus (GDM) and in eight age- and weight-m atched nondiabetic pregnant women during late gestation (third trimester) a nd again postpartum. Plasma glucose concentrations were raised to similar t o8.9 mM with iv glucose (hyperglycemic clamping), and ISRs were determined by deconvolution of peripheral C-peptide concentrations using C-peptide kin etic parameters that were obtained in every patient during late gestation a nd again postpartum. Plasma insulin levels were measured by RIA with an ant ibody with minimal (<0.2%) cross-reactivity with proinsulin. During late ge station, women with GDM were more insulin resistant than nondiabetic contro ls and had significantly lower ISRs (689 vs. 849 pmol/min, P < 0.05) and gl ucose uptake rates (30.6 vs. 49.4 mu mol/kg min, P < 0.05) in response to h yperglycemia. Postpartum, ISRs and insulin resistance decreased in women wi th GDM and controls (ISR by 43% and 43%, respectively, and insulin resistan ce by 75% and 118%, respectively), and both groups had similar ISRs (352 vs . 408 pmol/min, nonsignificant). Women with GDM, however, continued to be m ore insulin resistant than controls. In summary, patients with GDM during l ate pregnancy not only had severe deficiencies in ISR but, in addition, wer e more insulin resistant than controls. Postpartum, insulin resistance and ISRs (and plasma insulin levels) improved in both groups, and ISRs (and pla sma insulin levels) were no longer significantly different in patients with GDM and controls. Insulin resistance, however, remained higher in women wi th GDM, and their glucose uptake remained lower. We concluded that the wome n with GDM had a major <beta>-cell defect that made it impossible for them to compensate for their increased level of insulin resistance, which occurr ed during late pregnancy.