Sex Differences in Endothelial Function Markers Before Conversion to Pre-Diabetes: Does the Clock Start Ticking Earlier Among Women?

Abstract

We examined whether biomarkers of endothelial function, fibrinolysis/thrombosis and adiponectin, predict the progression from normal to pre-diabetes more strongly among women than men over 6 years of follow-up from the Western New York Health Study. In 2002-2004, 1,455 participants from the Western New York Health Study, who were free of type 2 diabetes and cardiovascular disease at baseline (1996-2001), were selected for reexamination. An incident case of pre-diabetes was defined as fasting glucose <100 mg/dl at the baseline examination and > or =100 and <126 mg/dl at the follow-up examination. Biomarkers of endothelial function (E-selectin and soluble intracellular adhesion molecule-1 [sICAM-1]), fibrinolysis/thrombosis (plasminogen activator inhibitor-1 [PAI-1]), and fasting insulin, adiponectin, and inflammation (high-sensitivity C-reactive protein) were measured in frozen (-190 degrees C) baseline samples. Multivariate analyses revealed higher adjusted mean values of biomarkers of endothelial dysfunction (E-selectin and sICAM-1) and fibrinolysis (PAI-1) and lower mean values of adiponectin only among women who developed pre-diabetes compared with control subjects. Formal tests for interaction between sex and case/control status were statistically significant for E-selectin (P = 0.042), PAI-1 (P = 0.001), sICAM-1 (P = 0.011), and frequency of hypertension (P < 0.001). These results support the concept that women who progressed from normoglycemia to pre-diabetes have greater endothelial dysfunction than men as well as more hypertension and a greater degree of fibrinolysis/thrombosis. Whether this relates to the higher risk of heart disease among diabetic women awaits further study.