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

Abstract

This study examined the association of HbA1c-defined glycemic status and continuous HbA1c with all-cause mortality. 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. 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). 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.