title: 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.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Göbl
authors.forename: Latife
authors.initials: L
authors.lastname: Bozkurt
authors.forename: Rajashri
authors.initials: R
authors.lastname: Yarragudi
authors.forename: Thomas
authors.initials: T
authors.lastname: Prikoszovich
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D050260:Carbohydrate Metabolism / Q000502:physiology*; D016640:Diabetes, Gestational / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D049590:Postpartum Period / Q000502:physiology*; D011247:Pregnancy; D014652:Vascular Diseases
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin