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

OBJECTIVE: Glycated hemoglobin (HbA(1c)) 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 HbA(1c) 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 HbA(1c) were estimated with Cox regression models. RESULTS: Relative to participants with an HbA(1c) of 5.4–5.6% (36–38 mmol/mol), participants with HbA(1c) ≥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 HbA(1c) was associated with increased risk of respiratory mortality. Levels <6.5% HbA(1c) 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: HbA(1c) 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.