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Chromium may improve insulin sensitivity, which can modify the risk of diabetes and cardiovascular disease (CVD). Therefore, we evaluated the association between toenail chromium and CVD in diabetic men.We performed cross-sectional and nested case-control analyses among men aged 40-75 years within the Health Professionals Follow-up Study. The cross-sectional analysis compared men with diabetes only (n = 688), diabetes with prevalent CVD (n = 198), and healthy control subjects (n = 361). The nested case-control study included 202 men with baseline diabetes who developed incident CVD and 361 matched control subjects.Mean toenail chromium (μg/g) was 0.71 in healthy control subjects, 0.61 in diabetes-only subjects, and 0.52 in diabetic subjects with prevalent CVD (P for trend = 0.003). In the cross-sectional analysis, the multivariate odds ratio (OR) between extreme quartiles was 0.74 (95% CI 0.49-1.11; P for trend = 0.18), comparing diabetes only with healthy control subjects. A similar comparison between diabetic subjects with prevalent CVD and healthy control subjects yielded an OR of 0.45 (0.24-0.84; P for trend = 0.003). In the nested casecontrol study, comparing diabetic men with incident CVD with healthy control subjects, the multivariate OR was 0.65 (0.36-1.17; P for trend = 0.16) between extreme quartiles. When we combined prevalent and incident CVD cases among diabetic men and compared them with healthy control subjects, the OR was 0.62 (0.39-1.01; P for trend = 0.02) between extreme quartiles.Our results suggest that diabetic men with CVD have lower toenail chromium than healthy control subjects. However, this study could not distinguish between the effects of chromium on diabetes and those on CVD. Long-term clinical trials are needed to determine whether chromium supplementation is beneficial for preventing CVD among diabetic patients.