1825-P: Reduced Insulin Clearance Compensates for Impaired ß-Cell Function to Maintain Normal Insulinemia in Normotolerant Women with History of Gestational Diabetes

Gestational diabetes (GDM) is one of the most common complications of pregnancy and it is frequently predictive of later maternal type 2 diabetes. A defect in insulin secretion is assumed to contribute to the development of GDM, which may be regarded as a prediabetic state. However, lean former GDM maintain normal insulinemia despite elevated glucose during oral test (OGTT).

Aim of this study was to evaluate some of the main processes involved in glucose tolerance in a large cohort of non-obese normotolerant former GDM. A total of 721 women participated in the study: 344 with recent GDM history (FGDM, 0.5-1 year after delivery; age=34±5 years, BMI=23±4 kg/m², HbA1c=36±5 nmol/mol) and 377 non-pregnant matching control women (32±12 years, 24±4 kg/m², p=0.3). All underwent 75g-3h OGTT with frequent sampling for glucose, insulin and C-peptide. Insulin sensitivity (OGIS, ml/minute m²) and insulin secretion from C-peptide (CPS, nmol) were assessed through mathematical modelling and deconvolution; beta cell function (BCF) as the ratio of the areas under the curves of C-peptide and glucose; insulin clearance (INCL) as the ratio CPS/AUC_INS. Data are given as mean±SD. FGDM had higher basal glucose (85±6 mg/dl vs. 82±7, p<0.0001), but similar insulin levels (7±6 µU/ml vs. 7±5, p=0.2). OGTT stimulated glucose was higher in FGDM (AUC_GLUC=19±3 minute g/dl vs. 17±3, p<0.0001); OGIS was analogous (521±63 vs. 530±67, p=0.1); BCF was lower in FGDM (342±88 nmol/mmol vs. 396±110, p<0.002), but AUC_INS was similar (37.8±24.6 minute nmol/l vs. 34.8±21.6, p=0.1). INCL was reduced (16.1±4.5 ml/minute vs. 18.7±5.8, p<0.0001).

Conclusion: non-obese, normotolerant FGDM are characterized by normal insulin sensitivity and reduced B-cell function. However, a concomitant reduction of insulin clearance acts to maintain relatively normal insulin levels, which however are not sufficient to keep a lower glycemia.