Sex Differences in Cardiovascular Risk Associated With Prediabetes and Undiagnosed Diabetes

INTRODUCTION: Women with Type 2 diabetes (T2D) face up to 50% higher risk of cardiovascular disease than men. This study evaluated the extent to which prediabetes and undiagnosed T2D are associated with a greater excess risk of cardiovascular disease in women versus in men. METHODS: Data were pooled from 18,745 cardiovascular disease-free individuals from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. The risk of coronary heart disease, ischemic stroke, and atherosclerotic cardiovascular disease (coronary heart disease or stroke) associated with prediabetes or undiagnosed T2D was estimated using Cox models adjusting for sociodemographic factors, concomitant risk factors, medication use, and menopausal status. Data were collected in 2022, and the analysis was performed in 2023. RESULTS: During a median follow-up of 18.6 years, the associations between prediabetes and risk of atherosclerotic cardiovascular disease were only significant in women (hazard ratio=1.18, 95% CI=1.01, 1.34, p=0.03) but not in men (hazard ratio=1.08, 95% CI=1.00, 1.28, p=0.06) (p-interaction=0.18). The associations between undiagnosed T2D and cardiovascular disease outcomes were significant in both sexes, but the effect was more pronounced in women (coronary heart disease: hazard ratio=1.83, 95% CI=1.4, 2.41, p<0.0001 in women vs hazard ratio=1.6, 95% CI=1.38, 2.07, p=0.007 in men; stroke: hazard ratio=1.99, 95% CI=1.39, 2.72, p<0.0001 vs hazard ratio=1.81, 95% CI=1.36, 2.6, p<0.0001; atherosclerotic cardiovascular disease: hazard ratio=1.86, 95% CI=1.5, 2.28, p<0.0001 vs hazard ratio=1.65, 95% CI=1.4, 1.98, p<0.0001) (all p-interactions≤0.2). Both White and Black patients exhibit similar sex differences. CONCLUSIONS: Prediabetes or undiagnosed T2D was associated with a greater excess risk of cardiovascular disease in women than in men. The sex differential in cardiovascular disease risk among those without the T2D diagnosis suggests the need for sex-specific guidelines in T2D screening and treatment.