Association between glycated hemoglobin A1c and diabetic retinopathy in adults with type 2 diabetes mellitus residing at high altitudes

Abstract

Aims To investigate the association between glycated hemoglobin A1c (HbA1c) and diabetic retinopathy (DR) in adults with type 2 diabetes mellitus (T2DM) at high altitude, and to explore potential effect modifiers. Methods This retrospective, hospital-based, cross-sectional study included 1040 adults with T2DM residing at high altitude in Qinghai Province, stratified into two altitude groups (1800–2500 m vs. ≥2500 m); no low-altitude comparison group was included. DR was diagnosed by fundus photography. Logistic regression, restricted cubic spline analyses, stratified and interaction analyses were performed. Results DR prevalence was 26.6% (n = 277). After full adjustment, each 1% increase in HbA1c was associated with higher odds of prevalent DR (OR 1.19, 95% CI 1.12-1.25), with no evidence of nonlinearity. Altitude did not significantly modify the association (P for interaction = 0.213). Significant effect modification was observed for estimated glomerular filtration rate (eGFR) (P for interaction = 0.031) and a borderline interaction was observed for body mass index (BMI) (P for interaction = 0.061). The association strengthened with lower eGFR (P for trend = 0.016) and higher BMI (P for trend = 0.013), being strongest in the low eGFR plus high BMI group (OR 1.38, 95% CI 1.20-1.59). Conclusions Among high-altitude adults with T2DM, HbA1c exhibited a linear positive association with prevalent DR; lower eGFR significantly modified this association, whereas the modifying trend linked to higher BMI remains exploratory and needs additional confirmation. These findings suggest that glycemic control, weight status, and renal function may need to be considered jointly when assessing DR burden in high-altitude populations.