Hemoglobin within normal range is negatively related to hemoglobin A1c in a nondiabetic American population aged 16 years and older

BACKGROUND: Protein glycosylated hemoglobin, hemoglobin A1c (HbA1c) binds hemoglobin (Hb) in red blood cells to blood glucose. However, the relationship between Hb and HbA1c remains unclear. AIM: To elucidate their relationship in a nondiabetic population aged ≥ 16 years in the United States, using data from the 1999-2018 National Health and Nutrition Examination Survey. METHODS: This study was based on data from 44560 adults aged ≥ 16 years, excluding those with diabetes. The relationship was estimated using a multivariate regression. We also used piecewise linear regression for subgroup analysis based on age and sex stratification and analysis of the threshold effects of Hb on HbA1c. RESULTS: Hb and HbA1c levels were negatively correlated in the unadjusted model (β = -0.01; 95%CI: -0.01, -0.01). The correlation was significantly negative when the regression model was minimally regulated and stratified by age and sex, and remained negative when the model was further regulated (more than 10%) to identify covariates with the HbA1c level influence estimates. In subgroup analyses based on age and sex stratification, the association remained negative when the covariates were controlled. A nonlinear relationship was observed between them when the Hb levels reached the tipping point (13.2 g/dL) (adjusted odds ratio, -0.04; 95%CI: -0.05, -0.03) and when the Hb levels exceeded 13.2 g/dL (adjusted odds ratio, -0.10; 95%CI: -0.10, -0.09). CONCLUSION: Our study shows that normal Hb levels are negatively correlated with HbA1c in nondiabetic Americans aged ≥ 16 years.