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 females predisposed for type 2 diabetes and cardiovascular disease. Endothelial dysfunction might represent a shared precursor of both disorders. Hence, this study aimed to characterize endothelial biomarkers in relation to impaired insulin 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 and underwent specific metabolic assessments including a frequently sampled intravenous glucose tolerance test and an 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 subtle inflammation. 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 visit predicted a later development of the disease (HR =1.02 95%CI 1.01 to 1.04, p = 0.013), however, this was attenuated after adjustment for BMI.

Conclusions: Elevated circulating markers of endothelial dysfunction in young females with GDM history might reflect an early stage on the pathway to the manifestation of future cardiometabolic disorders. Timely identification of women at high risk and optimization of follow-up management might provide an opportunity to prevent disease progression.

Figure 1

Bee swarm plot of endothelial biomarkers at baseline in different subgroups: normal glucose tolerant controls (NGT) as well as females after pregnancy with GDM grouped by insulin resistance status (pGDM-IS: insulin sensitive; pGDM-IR: insulin resistant): A: sICAM-1; B: sVCAM-1; C: sE-selectin. Lines indicate first, second (median) and third quartiles.

Figure 2

Association of baseline sICAM-1 (A), sVCAM-1 (B) and sE-selectin (C) with SI levels and the regression curve derived from regression analysis based on fractional polynomials.

Figure 3

Trajectories of soluble endothelial biomarkers in subjects after pregnancy with GDM categorized for diabetes progression (blue) or no progression (red) over the study period: sICAM-1 (A), sVCAM-1 (B), sE-selectin (C).

Figure 4

Bee swarm plot of IMT data in a subgroup of pGDM and controls: right side (A), left side (B), average (C). Lines indicate first, second (median) and third quartiles.