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

The Western New York Study

¹ Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, New York
² Department of Mathematics and Statistics, University of North Carolina, Charlotte, Charlotte, North Carolina

Address correspondence and reprint requests to Richard P. Donahue, PhD, MPH, Department of Social and Preventive Medicine, School of Public Health and Health Professions, State University of New York at Buffalo, 35 Main St., Farber Hall, Room 268 F, Buffalo, NY 14214. E-mail: rpd1{at}buffalo.edu

OBJECTIVE—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.

RESEARCH DESIGN AND METHODS—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 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°C) baseline samples.

RESULTS—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).

CONCLUSIONS—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.

Abbreviations: ACR, albumin-to-creatinine ratio • CHD, coronary heart disease • CVD, cardiovascular disease • HOMA-IR, homeostasis model assessment of insulin resistance • hsCRP, high-sensitivity C-reactive protein • PAI-1, plasminogen activator inhibitor-1 • sICAM-1, soluble intracellular adhesion molecule-1

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