Rising plasminogen activator inhibitor-1 and hypoadiponectinemia characterize the cardiometabolic biomarker profile of women with recent gestational diabetes

Background: Gestational diabetes (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women at risk of developing type 2 diabetes and cardiovascular disease later in life. Accordingly, the postpartum years after gestational dysglycemia can provide insight into early events in the natural history of these disorders. We thus sought to prospectively evaluate the relationship between gestational glucose tolerance and emerging cardiometabolic biomarkers [adiponectin, chemerin, retinol-binding protein-4 (RBP-4), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1)] at both 1- and 3-years postpartum in a cohort reflecting the full spectrum of gestational dysglycemia (from normal to GIGT to GDM). Methods: Three-hundred-and-thirty-nine women completed a glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, which identified 4 gestational glucose tolerance groups: GDM (n = 105); GIGT (n = 59); abnormal GCT with normal OGTT (n = 99); and normal GCT with normal OGTT (n = 76). At 1- and 3-years postpartum, the women underwent repeat OGTT with measurement of biomarkers (adiponectin/chemerin/RBP-4/CRP/PAI-1). Results: Serum adiponectin was lower in women with GDM and GIGT at both 1-year and 3-years (both P <= 0.002), whereas chemerin, RBP-4, CRP and PAI-1 showed no differences across the 4 groups. Importantly, the change in PAI-1 between 1- and 3-years progressively increased from the normal GCT group to the abnormal GCT group to GIGT to GDM (P = 0.03). Indeed, both GDM (t = 2.98, P = 0.003) and GIGT (t = 2.14, P = 0.03) independently predicted an increase in PAI-1 from 1- to 3-years postpartum. Conclusions: Hypoadiponectinemia and rising PAI-1 over time are early features of the cardiometabolic biomarker profile of women with recent gestational dysglycemia.