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A Meta-analysis of Prospective Studies

Emily B. Levitan, ScB; Yiqing Song, MD; Earl S. Ford, MD, MPH; Simin Liu, MD, ScD

Arch Intern Med. 2004;164:2147-2155.

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/L]) (RR, 1.27 [95% CI, 1.09-1.48]). The results were similar when combining studies regardless of type of blood glucose assessment (RR, 1.36 [95% CI, 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, 1.07-1.32]). 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.

Author Affiliations: Division of Preventive Medicine, Harvard Medical School and Brigham and Women’s Hospital (Ms Levitan and Drs Song and Liu), and Department of Epidemiology, Harvard School of Public Health (Ms Levitan and Drs Song and Liu), Boston, Mass; and Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Ford).

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