Gender Differences in Diabetes and Risk of Incident Coronary Artery Disease in Healthy Young and Middle-Aged Adults

  1. Dhananjay Vaidya, PhD, MPH2
  1. 1Division of Endocrinology, Johns Hopkins University, Baltimore, Maryland
  2. 2Division of General Internal Medicine, Johns Hopkins University, Baltimore, Maryland
  3. 3Division of Cardiology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland
  4. 4Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
  1. Corresponding author: Rita Rastogi Kalyani, E-mail: rrastogi{at}


Objective Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated gender differences in CAD by diabetes-status among healthy individuals with different underlying risks of heart disease.

Research Design/Methods We examined subjects aged<60 years without CAD at enrollment in the high-risk GeneSTAR Study (n=1448;follow-up∼12years), Multi-Ethnic Study of Atherosclerosis (n=3072;follow-up∼7years) and NHANES III Mortality Follow-up Study (n=6997;follow-up∼15years). Diabetes was defined by report, hypoglycemics use, and/or fasting glucose≥126 mg/dl. The outcome was any CAD event during follow-up (fatal CAD in NHANES).

Results In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, 0.40/1000 person-years,respectively) versus men (11.22, 5.64, 0.88/1000 person-years); log-rank p-value<0.001(GeneSTAR/MESA) and p=0.07(NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, 2.37/1000 person-years) versus men (12.86, 9.71, 1.83/1000 person-years); all log-rank p-value>0.05. Adjusting for demographics, diabetes was associated with a significant four-to-five-fold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for body-mass index,smoking,hypertension,HDL and non-HDL cholesterol,anti-hypertensive and cholesterol-lowering medication use, the hazard ratio(HR) of CAD in men versus women among non-diabetes was 2.43(1.76-3.35) and diabetes 0.89(0.43-1.83), p=0.013 interaction by diabetes-status.

Conclusions Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by gender. Our findings support aggressive CAD prevention strategies in women with diabetes, and at similar levels to those that exist in men.

  • Received July 25, 2013.
  • Accepted October 22, 2013.

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