Association between hemoglobin A1c and all-cause mortality: results of the mortality follow-up of the German National Health Interview and Examination Survey 1998.

OBJECTIVE This study examined the association of HbA1c-defined glycemic status and continuous HbA1c with all-cause mortality. RESEARCH DESIGN AND METHODS The study population comprised 6,299 participants (aged 18-79 years) of the German National Health Interview and Examination Survey 1998, who were followed up for mortality for an average of 11.6 years. Glycemic status was defined as known diabetes (self-reported diagnosis or intake of antidiabetic medication) and based on HbA1c levels according to American Diabetes Association diagnostic criteria as undiagnosed diabetes (≥6.5% [≥48 mmol/mol]), prediabetes with very high (6.0-6.4% [42-46 mmol/mol]) or high diabetes risk (5.7-5.9% [39-41 mmol/mol]), and normoglycemia (<5.7% [<39 mmol/mol]). Associations between glycemic status and mortality were examined by Cox regression adjusting for age, sex, education, lifestyle factors, anthropometric measures, and history of chronic diseases (reference: normoglycemia). Spline models were fitted to investigate associations between continuous HbA1c and mortality among participants without known diabetes. RESULTS Excess mortality risk was observed for participants with known diabetes (hazard ratio 1.41 [95% CI 1.08-1.84]) and undiagnosed diabetes (1.63 [1.23-2.17]) but not for those with high (1.02 [0.80-1.30]) or very high diabetes risk (0.87 [0.67-1.13]). Spline models revealed a U-shaped association, with lowest risk at HbA1c levels 5.4-5.6% (36-38 mmol/mol) and a significantly increased risk at ≤5.0% (≤31 mmol/mol) and ≥6.4% (≥46 mmol/mol). CONCLUSIONS Unlike known and undiagnosed diabetes, HbA1c levels in the prediabetic range were not associated with an increased mortality risk. The observed U-shaped relationship adds to existing evidence that not only high but also low HbA1c levels might be associated with all-cause mortality.