Low Hemoglobin A1c in Nondiabetic Adults

Abstract

OBJECTIVE To identify predictors of low hemoglobin A1c (HbA1c) (<5.0%) and to investigate the association of low HbA1c with cause-specific mortality and risk of liver disease hospitalization. RESEARCH DESIGN AND METHODS Prospective cohort study of 13,288 participants in the Atherosclerosis Risk in Communities Study. Logistic regression was used to identify cross-sectional correlates of low HbA1c, and Cox proportional hazards models were used to estimate the association of low HbA1c with cause-specific mortality. RESULTS Compared with participants with HbA1c in the normal range (5.0 to <5.7%), participants with low HbA1c were younger, less likely to smoke, had lower BMI, lower white cell count and fibrinogen levels, and lower prevalence of hypercholesterolemia and history of coronary heart disease. However, this group was more likely to have anemia and had a higher mean corpuscular volume. In adjusted Cox models with HbA1c of 5.0 to <5.7% as the reference group, HbA1c <5.0% was associated with a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.32, 95% CI: 1.13–1.55) and of cancer death (1.47, 95% CI: 1.16–1.84). We also noted nonsignificant trends toward increased risk of death from cardiovascular causes (1.27, 95% CI: 0.93–1.75) and respiratory causes (1.42, 95% CI: 0.78–2.56). There was a J-shaped association between HbA1c and risk of liver disease hospitalization. CONCLUSIONS No single cause of death appeared to drive the association between low HbA1c and total mortality. These results add to evidence that low HbA1c values may be a generalized marker of mortality risk in the general population.