Biomarkers of vascular injury and endothelial dysfunction after recent glucose intolerance in pregnancy

Objective: Women with gestational diabetes mellitus and milder gestational impaired glucose intolerance have elevated future risks of type 2 diabetes and cardiovascular disease. However, it is unclear whether they show postpartum evidence of vascular injury/dysfunction, an early event in the natural history of cardiovascular disease. Methods: In total, 337 women underwent a glucose challenge test and oral glucose tolerance test in pregnancy, yielding four gestational glucose tolerance groups: gestational diabetes mellitus, gestational impaired glucose intolerance, abnormal glucose challenge test with normal glucose tolerance on the oral glucose tolerance test and normal glucose challenge test with normal glucose tolerance. At 3years postpartum, they underwent repeat oral glucose tolerance test (on which 69 women had pre-diabetes/diabetes) and measurement of the following serum markers of vascular injury/dysfunction: thrombomodulin, E-selectin, P-selectin, intercellular adhesion molecule-3 and vascular cell adhesion molecule-1. Results: At 3years postpartum, mean adjusted vascular cell adhesion molecule-1 was the only vascular marker that differed across the previous gestational glucose tolerance groups. On multiple linear regression analysis, each strata of gestational dysglycaemia was an independent predictor of lower vascular cell adhesion molecule-1 at 3years postpartum (gestational diabetes mellitus: p=0.005; gestational impaired glucose intolerance: p=0.003; abnormal glucose challenge test normal glucose tolerance: p=0.0008), as was current pre-diabetes/diabetes (p=0.01). Conclusion: Dysregulation of vascular cell adhesion molecule-1 may be an early event in the natural history of cardiovascular disease in women with recent glucose intolerance in pregnancy.