Diabetic retinopathy as a marker for renal cell carcinoma among patients with type 2 diabetes mellitus.

Abstract

486 Background: Type 2 diabetes mellitus (T2DM) has been associated with increased risk of renal cell carcinoma (RCC). Animal studies indicate that glucose dysregulation and elevated insulin/IGF-1 signaling cascade accelerate renal tumorigenesis. Epidemiological studies suggest that greater severity of T2DM, defined by the number of complications and actively using glucose-lowering agents, is associated with higher RCC risk. Diabetic retinopathy (DR), readily detected during routine ophthalmology visits, can serve as a practical, objective marker of T2DM severity. However, few studies have directly examined the association between DR and RCC. In this study, we aim to evaluate whether the presence of DR increases the risk of RCC in patients with T2DM and to propose its potential as a clinical indicator for RCC screening. Methods: We conducted a case–control study using the All of Us Research Program Registered Tier v8 dataset. Adults with T2DM were identified by ICD-10 codes, excluding patients with RCC prior to T2DM diagnosis. DR was defined as non-proliferative and proliferative DR using ICD-10 codes. We fit multivariable logistic regression models to evaluate the association between DR to RCC status, adjusted for age, sex at birth, race, ethnicity, body mass index, and smoking status. Results: We identified 67,096 patients with T2DM. Among them, 7,320 (10.9%) had DR and 603 (0.9%) had RCC. Compared with patients without DR, those with DR were older (66.4 vs 64.4), more often male (49.6% vs 42.6%), and had lower smoking prevalence (43.6% vs 46.5%). RCC prevalence was 1.46% in the DR group vs 0.83% in the non-DR group. In multivariable analyses, DR was associated with higher odds of RCC (OR =1.58, 95% CI 1.27–1.98, p<0.001). In sex-stratified analyses, the association remained significant in both sex groups, with a slightly larger effect in men (male: OR =1.67, 95% CI 1.25-2.22, p<0.001; female: OR 1.60, 95% CI 1.10-2.33, p=0.015). Conclusions: DR was associated with higher odds of RCC compared with DM alone. These findings support considering RCC screening after DR diagnosis and the need for studies to evaluate the benefits, harms, and cost-effectiveness of DR-guided screening.