Age and HbA1c in Diabetes: A Negative Association Modified by Red Cell Characteristics

Abstract

Background: While a positive correlation between age and HbA1c has been suggested in non-diabetic individuals, warranting higher HbA1c reference ranges for older adults, evidence among individuals with diabetes is less clear and may reveal an inverse trend. This study aimed to examine the relationship between age and HbA1c in a diabetic population, considering red cell parameters and other confounding factors; Methods: This cross-sectional study included 268 diabetic participants from Mongolia-Japan University Hospital (mean age 57.0 ± 9.9 years, 38.8% male, median diabetes duration 8.0 years, mean HbA1c 9.2 ± 3.3%). We analyzed the association between age and HbA1c using linear regression models, adjusting for diabetic characteristics, chronic complications, inflammation markers, and red cell indices. Subgroup analyses were conducted based on red cell distribution width (RDW) median splits; Results: A significant negative association between age and HbA1c was observed, with an unstandardized B coefficient (95% CI) of −0.112 (−0.166; −0.058, p < 0.001). This association persisted after adjustment for diabetic characteristics, complications, inflammation markers, and red cell indices (−0.115, −0.179; −0.051, p = 0.001). Subgroup analyses indicated a stronger negative association in participants with lower RDW levels (−0.174, −0.269; −0.079, p < 0.001) compared to those with higher RDW (−0.080, −0.147; −0.014, p = 0.019), suggesting that red cell characteristics may modify this relationship. No significant interactions were identified except for RDW; Conclusions: Our findings reveal a distinct negative association between age and HbA1c in diabetic individuals, independent of diabetic characteristics, complications, and inflammation markers. This association is particularly pronounced in individuals with lower RDW levels, highlighting the potential role of red cell morphology in influencing HbA1c levels with aging in diabetes.