Sex Differences in the Association between Hemoglobin A1c and Cerebral White Matter Lesions in the General Japanese Population

Abstract

The influence of diabetes and associated sex differences on cerebral white matter lesions (WML) is unclear. We used data from a cross-sectional study uploaded to the DATADRYAD website by Shinkawa et al. to investigate differences in the association between hemoglobin A1c (HbA1c) levels and cerebral WML between men and women. The average age of all participants was 56.4 ± 11.5 years old, and approximately 51.89% of them were men. A linear relationship between HbA1c and cerebral WML was detected in men. Fully adjusted binary logistic regression showed no association of HbA1c with cerebral WML in men. A nonlinear relationship between HbA1c and cerebral WML was detected in women, whose cutoff point was 5.6%. The effect sizes and confidence intervals of the left and right sides of the inflection point were OR = 0.21 (95% CI 0.06, 0.69, P = 0.0098) and OR = 3.5 (95% CI 1.50, 8.15, P = 0.0037), respectively. In the higher HbA1c group, further subgroup analysis showed a stronger association between HbA1c and cerebral WML in women (OR = 3.83, 95% CI 1.68, 8.72 P = 0.0014) than in men (OR = 1.02, 95% CI 0.76, 1.36 P = 0.8986) (P for interaction with sex was 0.0004). A stronger effect of HbA1c on the risk of cerebral WML in women than in men was found in the higher HbA1c group.