Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies

Background: Although hyperglycemia increases the risk of cardiovascular disease (CVD) in diabetic patients, the risk associated with blood glucose levels in the nondiabetic range remains unsettled. Methods: We identified 38 reports in which CVD incidence or mortality was an end point, blood glucose levels were measured prospectively, and the relative risk (RR) and information necessary to calculate the variance were reported comparing groups of nondiabetic people. These reports were prospective studies, published in English-language journals. First author, publication year, participant age and sex, study duration, CVD end points, glucose assessment methods, control for confounding, range of blood glucose levels, RR, and confidence intervals (CIs) or P values were extracted. Using a random effects model, we calculated pooled RRs and 95% CIs. Results: The group with the highest postchallenge blood glucose level (midpoint range, 150-194 mg/dL [8.3-10.8 mmol/L]) had a 27% greater risk for CVD compared with the group with the lowest level (midpoint range, 69-107 mg/dL [3.8-5.9 mmol/Ll) (RR, 1.27 [95% Cl, 1.091.48]). The results were similar when combining studies regardless of type of blood glucose assessment (RR, 1.36 [95% Cl, 1.23-1.52]) and when using strict criteria for exclusion of diabetic subjects (RR, 1.26 [95% CI, 1.11-1.43]). Adjustment for CVD risk factors attenuated but did not abolish this relationship (RR, 1.19 [95% CI, 1.071.321). The RR was greater in cohorts including women than in cohorts of men (RR, 1.56 vs; 1.24 [P=.03]). Conclusion: Blood glucose level is a risk marker for CVD among apparently healthy individuals without diabetes.