Biomarkers of endothelial dysfunction in relation to impaired carbohydrate metabolism following pregnancy with gestational diabetes mellitus

Abstract

Background: History of gestational diabetes mellitus (GDM) identifies a very young population of femalespredisposed for type 2 diabetes and cardiovascular disease. Endothelial dysfunction might represent a sharedprecursor of both disorders. Hence, this study aimed to characterize endothelial biomarkers in relation to impairedinsulin sensitivity and progression to overt diabetes early after index pregnancy.Methods: 108 women with previous GDM and 40 controls were included three to six months after delivery andunderwent specific metabolic assessments including a frequently sampled intravenous glucose tolerance test andan oral glucose tolerance test. Diabetes progression was assessed in females with pGDM over 10 years of follow-up.Circulating sICAM-1 (intracellular-adhesion-molecule-1), sVCAM-1 (vascular-cell-adhesion-molecule-1) and sE-selectin,representing biomarkers of endothelial dysfunction were assessed at baseline and annually over five years.Results: Endothelial biomarkers were significantly associated with insulin sensitivity (sICAM-1: r = -0.23, p = 0.009;sVCAM-1: r = -0.22, p = 0.011; sE-selectin: r = -0.21, p = 0.018) as well as with GDM status and parameters of subtleinflammation. Analysis of long-term trajectories revealed constantly elevated sICAM-1 (p = 0.033) and sE-selectin(p = 0.007) in 25 subjects with diabetes progression. Accordingly, sE-selectin levels at the early post partum visitpredicted a later development of the disease (HR =1.02 95%CI 1.01 to 1.04, p = 0.013), however, this was attenuatedafter adjustment for BMI.Conclusions: Elevated circulating markers of endothelial dysfunction in young females with GDM history mightreflect an early stage on the pathway to the manifestation of future cardiometabolic disorders. Timely identificationof women at high risk and optimization of follow-up management might provide an opportunity to prevent diseaseprogression.