Glycated Hemoglobin and All-Cause and Cause-Specific Mortality in Singaporean Chinese Without Diagnosed Diabetes: The Singapore Chinese Health Study

OBJECTIVE: Glycated hemoglobin (HbA₁c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA₁c and mortality in a cohort of Southeast Asians. RESEARCH DESIGN AND METHODS: Analysis of 7,388 men and women, mean age 62 years, from the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and reported no history of diabetes, previous adverse cardiovascular events, or cancer. A total of 888 deaths were identified through 31 December 2011 via registry linkage. Participants represented a random study sample of potential control subjects for a nested case-control genome-wide association study of type 2 diabetes in the population. Hazard ratios (HRs) for all-cause and cause-specific mortality by six categories of HbA1c were estimated with Cox regression models. RESULTS: Relative to participants with an HbA₁c of 5.4-5.6% (36-38 mmol/mol), participants with HbA₁c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56-2.46), 2.63 (1.77-3.90), and 1.51 (1.04-2.18), respectively. No level of HbA1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA₁c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post-blood draw. CONCLUSIONS: HbA₁c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women.