Fibrinolytic dysfunction after gestation is associated to components of insulin resistance and early type 2 diabetes in latino women with previous gestational diabetes

Abstract

Among patients with metabolic syndrome (MS), atherosclerosis and abnormal fibrinolytic function are frequently present, mostly owing to an increase in plasminogen activator inhibitor-1(PAI-1). We analyze PAI-1 in pregnant women, both normal and with gestational diabetes (GDM) and postpartum regarding its correlation to MS surrogates. Clinical characteristics, glucose tolerance (100g-OGTT), lipids, PAI-1 antigen, insulin sensitivity (HOMA-S), and pancreatic β-cell function (HOMA-B) were investigated in 34 women. Eleven had normal glucose tolerance (NGT) during pregnancy and 23 had GDM (all GAD antibodies-negative). All patients were studied at 28–34 weeks of gestation and 16–24 weeks after delivery (75g-OGTT). Parameters of interest were determined using commercial test systems. During pregnancy, PAI-1 was not statistically different between NGT and GDM (47±25ng/ml versus 47±28ng/ml, p=0.9). After gestation, 19 (56%) women had NGT (11 of them from previous NGT group) and 15 (44%) had impaired glucose tolerance (IGT) or DM. The IGT (IGT+DM) group had higher PAI-1 (p=0.01), which did not decreased after delivery NGT–NGT before and after delivery (47±25ng/ml versus 6±5ng/ml; p<0.001), GDM–NGT (62±36ng/ml versus 14±15ng/ml; p=0.001) and GDM–IGT (39±20ng/ml versus 27±23ng/ml; p=0.15). PAI-1 levels were positively correlated (p<0.05) to total cholesterol (rs=0.37), triglycerides (rs=0.48), fasting plasma glucose (rs=0.52), 2-h plasma glucose in the OGTT (rs=0.58) and were negatively correlated (p<0.05) with HOMA-S (rs=−0.42) and HOMA-B (rs=−0.38). Fibrinolytic dysfunction is still present in GDM women and is associated with early development of IGT or T2DM. PAI correlated with surrogate markers of MS levels and may identify a group of women at risk for macroangiopathy.