Coronary vascular dysfunction in premenopausal women with diabetes mellitus

Background Diabetes mellitus abolishes the sex differential in coronary artery disease morbidity and mortality in premenopausal women. This finding is independent of other diabetes-associated risk factors, suggesting that other mechanisms such as impaired coronary vascular function may contribute to the increased cardiovascular risk in women with diabetes. The objective of this study was to investigate the effect of diabetes on coronary vascular function in premenopausal women. Methods We studied 13 premenopausal women with diabetes (aged 41 ± 10 years) who were free of overt cardiovascular complications, and 21 control women (12 age-matched and 9 postmenopausal [aged 56 ± 8 years]). We used [13N]-ammonia as the flow tracer and positron emission testing to measure myocardial blood flow (MBF) at rest, during maximal hyperemia, and in response to cold pressor testing. Results Baseline MBF was lower in the postmenopausal controls, reflecting the differences in cardiac work and oxygen demand as assessed by the rate-pressure product. However, baseline MBFs were similar in the 3 groups after normalization for differences in the rate-pressure product. During hyperemia, MBF increased and coronary vascular resistance decreased significantly in the 3 groups. However, the increase (from baseline) in MBF in the women with diabetes (164% ± 58%) was less than in the premenopausal controls (258% ± 81%, P = .021), but not significantly different from the postmenopausal control women (204% ± 104%, P = .51). Likewise, the increase in MBF in response to cold pressor testing in the women with diabetes (24% ± 19%) was significantly lower than in the premenopausal controls (60% ± 39%, P = .013), but similar to that in postmenopausal control women (27% ± 15%, P = .97). These differences persisted after adjusting for age and diabetes-associated metabolic abnormalities. Conclusions These results demonstrate reduced coronary vasodilator function and impaired response of resistance vessels to increased sympathetic stimulation in premenopausal women with diabetes, similar to those observed in healthy postmenopausal women in whom the sex differential in coronary artery disease morbidity and mortality is no longer present. (Am Heart J 2002;144:711-8.)