Meta-Analysis: Glycosylated Hemoglobin and Cardiovascular Disease in Diabetes Mellitus

In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear. PURPOSE: To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons. DATA SOURCES: Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease. STUDY SELECTION: Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease. DATA EXTRACTION: Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria. DATA SYNTHESIS: Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1-percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43]).

This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results.