Abstract MP60: Prediabetes and Undiagnosed Diabetes Predisposing Women to Excess Risk of Cardiovascular Disease

Abstract

Objective: Women with type 2 diabetes (T2DM) have a 25-50% higher risk of cardiovascular disease (CVD) than their men counterparts. The reasons for this sex disparity are incompletely understood. We sought to examine if pre-diabetes (preDM) and undiagnosed T2DM are associated with a greater magnitude of CVD risk in women than in men. Methods: We pooled CVD-free individuals (N=18,745) from the Atherosclerosis Risk in Communities, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. CVD outcomes included incident coronary heart disease (CHD) (myocardial infarction, CHD death, or cardiac procedures including percutaneous coronary interventions, bypass surgery, or coronary revascularization), stroke (ischemic or hemorrhagic stroke), and a composite atherosclerotic CVD (ASCVD) (any CHD condition or stroke). Multivariable Cox models examined the outcomes associated with preDM (fasting glucose [FG] 100-125 mg/dL or HbA1c 5.7-6.4%) or undiagnosed T2DM (FG ≥126 mg/dL or HbA1c ≥6.5% and without a DM diagnosis or anti-diabetes medication use) adjusted for age, race/ethnicity, education, BMI, blood pressure, total cholesterols, smoking, anti-hypertensive and lipid-lowering medications, and cohort indicator. An interaction term sex x preDM or undiagnosed DM was added to models to test the sex modifying effect. We consider p-interaction<0.2 as significant. Results: During a median follow-up of 17 years, the adjusted model showed that preDM was significantly associated with a higher risk of CHD (Hazard ratio 1.09, 95%CI 1.04-1.14), stroke (1.08, 1.04-1.13), and ASCVD (1.09, 1.04-1.14) in women, but not in men (1.04, 0.99-1.1 for CHD, 1.03, 0.98-1.08 for stroke, and 1.03, 0.98-1.09 for ASCVD, respectively). Undiagnosed T2DM was significantly associated with the risk of CHD (1.27, 1.16-1.4 in women and 1.17, 1.05-1.3 in men), stroke (1.32, 1.21-1.45 in women and 1.2, 1.09-1.32 in men), and ASCVD (1.27, 1.16-1.4 in women and 1.15, 1.03-1.29 in men) in both sexes but with more pronounced effect in women (P-interactions ≤0.11). In racial-stratified analysis, a higher magnitude of CVD risk associated with preDM or undiagnosed DM was also found in non-Hispanic (NH) white women and NH-black women than in their men counterparts. Conclusions: PreDM and undiagnosed DM predispose women to excess CVD risk, possibly due to women’s higher susceptibility to metabolic dysfunction at a lower glucose level and the prolonged unmanaged time for risk factors relative to men. T2DM screening and risk factor control should be enhanced in both sexes to reduce future CVD risk, particularly in women.