Age at diabetes onset modifies the association between hyperuricemia and diabetic retinopathy: a real-world cross-sectional study.

Authors

Minghua Fan, Jun Li, Qiuju Zhou, Hui Shao, Lisha Ni

Published in

Endocrine. Volume 91. Issue 1. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

The role of hyperuricemia in diabetic retinopathy (DR) remains controversial, with limited evidence on how age at diabetes onset modifies this association. This study aimed to investigate the differential association of elevated uric acid (UA) with DR prevalence stratified by age at diagnosis.
We analysed cross-sectional data from 6,996 patients with type 2 diabetes mellitus, grouped by age at diabetes onset (younger-onset, < 65 years; older-onset, ≥ 65 years) and UA status (normal vs. elevated: ≥420 µmol/L for men; ≥380 µmol/L for women). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for the cross-sectional association between UA and prevalent DR. Pre-specified subgroup analyses with multiplicative interaction terms were conducted to explore whether this association differed across strata, with exact P-values reported; these analyses are exploratory and hypothesis-generating. Sensitivity analyses were performed using alternative age cutoffs (40, 50, 60 years), and variance inflation factors (VIFs) were calculated to evaluate collinearity between age at onset and diabetes duration.
A total of 1,359 prevalent DR cases were identified among 6,996 participants. Elevated UA was significantly associated with higher odds of prevalent DR in younger-onset diabetes (aOR = 1.42, 95% CI: 1.17-1.73) but not in older-onset diabetes (aOR = 1.05, 95% CI: 0.61-1.79). However, a formal test for interaction between UA and age-at-onset group was not statistically significant (P-interaction = 0.295), indicating that the present data do not establish age at onset as an effect modifier; the older-onset stratum was small (992 patients, 116 DR events) and its estimate was correspondingly imprecise. The younger-onset association was robust to additional adjustment for albuminuria (aOR = 1.37, 95% CI: 1.12-1.67) and to a fully expanded model further adjusting for smoking, alcohol, urate-lowering therapy, and hypertension severity (aOR = 1.38, 95% CI: 1.12-1.70). Restricted cubic spline modelling showed a positive, approximately linear UA-DR relationship with no significant departure from linearity (P-nonlinearity = 0.31). When stratified by DR severity, elevated UA was more strongly associated with proliferative DR (aOR = 2.39, 95% CI: 1.24-4.61) than with non-proliferative DR (aOR = 1.31, 95% CI: 1.09-1.58). The E-value for the younger-onset association was 1.67 (lower confidence limit 1.38). Findings were consistent across alternative age cutoffs.
In this cross-sectional analysis, elevated UA was independently associated with higher odds of prevalent DR among patients with younger-onset type 2 diabetes, whereas no significant association was detected in the smaller older-onset group. A formal interaction test was not significant, so the data do not establish age at onset as a true effect modifier, and the apparent contrast between strata should be interpreted cautiously. The younger-onset association was robust to adjustment for albuminuria and other potential confounders and was stronger for proliferative than non-proliferative disease. Given the cross-sectional design, prospective longitudinal studies are needed to establish temporality and to confirm whether this association is causal.

PMID:
42455242
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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