Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis

PLoS One. 2012;7(8):e42551. doi: 10.1371/journal.pone.0042551. Epub 2012 Aug 9.


Background: Chronic hyperglycemia in type 2 diabetes increases the risk of microvascular events. However, there is continuing uncertainty about its effect on macrovascular outcomes and death. We conducted a meta-analysis of prospective studies to estimate the association of glycosylated hemoglobin level with the risk of all-cause mortality and cardiovascular outcomes among patients with type 2 diabetes.

Methodology/principal findings: We systematically searched the MEDLINE database through April 2011 by using Medical Subject Heading search terms and a standardized protocol. We included prospective cohort studies that reported data of glycosylated hemoglobin level on the risk of incident cardiovascular events and all-cause mortality. Relative risk estimates (continuous and categorical variables) were derived or abstracted from each cohort study. Twenty six studies were included in this analysis with a mean follow-up rang of 2.2-16 years. The pooled relative risk associated with a 1% increase in glycosylated hemoglobin level among patients with type 2 diabetes was 1.15 (95% CI, 1.11 to 1.20) for all-cause mortality, 1.17 (95% CI, 1.12 to 1.23) for cardiovascular disease, 1.15 (95% CI, 1.10 to 1.20) for coronary heart disease, 1.11 (95% CI, 1.05 to 1.18) for heart failure, 1.11 (95% CI, 1.06 to 1.17) for stroke, and 1.29 (95% CI, 1.18 to 1.40) for peripheral arterial disease, respectively. In addition, a positive dose-response trend existed between glycosylated hemoglobin level and cardiovascular outcomes.

Conclusions/significance: Chronic hyperglycemia is associated with an increased risk for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes, likely independently from other conventional risk factors.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / mortality*
  • Diabetes Mellitus, Type 2 / complications*
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Prognosis


  • Glycated Hemoglobin A

Grant support

This work was supported by Guanghua Scholarship Fund from Xi’an Jiaotong University (No. GH 0203106), the National Natural Science Foundation of China (No. 50976088), and Louisiana State University’s Improving Clinical Outcomes Network (LSU ICON). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.