Abstract 14149: Gender Differences in the Association of Diabetes with Incident Coronary Heart Disease in Two Populations

Abstract

Objective: Controversy exists about the coronary disease risk conveyed by diabetes in women vs men. We explored gender differences in risk of CHD conveyed by diabetes among high-risk adults and a representative U.S. population.

Methods: We examined subjects without clinical CHD in the GeneSTAR study (all with family history of premature CHD, n=1448; 54% women; median [IQR] 47 [42-52] yrs), and NHANES III mortality follow-up study (n=9440; 54% women; median 40 [30-54] yrs; 7.2% family history CHD). Diabetes was defined by report, use of hypoglycemics, or fasting glucose >126 mg/dl. Normal status was fasting glucose <100 mg/dl. CHD was ascertained by interview/records in GeneSTAR; in NHANES, only fatal CHD events were included. Risk of incident CHD was examined using Cox proportional hazards models.

Results: Over a median 12.3 yrs in GeneSTAR, 27% of men and 23% of women with diabetes had incident CHD (vs 23% and 8% in normals). Over 14.4 yrs in NHANES III, 11% of men and 10% of women with diabetes had incident CHD (vs 2.7% and 2.3% in normals; see K-M curves in Figure). Accounting for age, race, education, diabetes vs normal status was associated with increased CHD in women (GeneSTAR HR=3.06, 95% CI 1.68-5.56; NHANES III HR=2.48, 1.47-4.19) but not men (GeneSTAR HR=1.16,0.68-1.98; NHANES III HR=1.27, 0.79-2.04). Interaction by gender was significant for GeneSTAR (p=0.01) with trend towards significance for NHANES III (p=0.11). Results were similar after adjusting for BMI, smoking, hypertension, total and HDL cholesterol.

Conclusions: A strong independent association of diabetes with incident CHD was observed in women but not men in two relatively young cohorts. Men with normal glucose and premature family history have a high risk of CHD. Thus, the effect of diabetes as a CHD risk factor may be attenuated in men and/or diabetes truly confers a greater risk to women. Unraveling this gender difference can help identify mechanisms and develop strategies for gender-targeted prevention.