Diabetes Mellitus, Cumulative Glucose Exposure, and Incident Cardiovascular Disease Risk.

BACKGROUND: Diabetes mellitus is associated with dyslipidemia, elevated blood pressure, and increased risk for incident cardiovascular disease (CVD). OBJECTIVES: This study examined whether diagnosed diabetes before age 40 years is associated with incident CVD risk independent of other measured risk factors. It also evaluated whether cumulative glucose exposure from young adulthood to age 40 years is associated with subsequent CVD risk and explored the relative contribution of diabetes compared with other CVD risk factors. METHODS: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we created a sequential propensity-score-matched sample at age 40 years: Each participant with diabetes was matched to one prediabetes participant and up to 2 without diabetes. Cox proportional hazards regression models were used to assess associations of diabetes and cumulative glucose exposure with incident CVD and its components: coronary heart disease, stroke, and congestive heart failure. RESULTS: Of 4,931 individuals, 766 propensity-score-matched participants experienced 103 incident CVD events during a median 22-year follow-up after age 40 years. Diagnosed diabetes was independently associated with incident CVD after adjustment for other known risk factors (HR: 2.13; 95% CI: 1.33-3.41 for diabetes vs nondiabetes, P = 0.002); CVD risk rose as cumulative glucose exposure increased. Among matched participants, the excess CVD rate associated with diabetes was greater than the rate difference associated with other cardiovascular risk factors commonly elevated in diabetes. CONCLUSIONS: Diabetes by age 40 years was associated with higher subsequent CVD risk beyond established risk factors, with CVD risk increasing as cumulative glucose exposure rose.