Relationship between diabetic retinopathy stages and risk of major lower-extremity arterial disease in patients with type 2 diabetes

<b>Objective. </b>We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors in this relationship in a prospective cohort of patients with type 2 diabetes. <p><b>Research design and methods</b><b>. </b>Diabetic retinopathy was staged at baseline as absent, non-proliferative or proliferative. Cox regression model was fitted to compute HR (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. Retinopathy-LEAD association was assessed in subgroups by age, gender, diabetes duration, HbA1c, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy to stratify LEAD risk was assessed using c-statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI).<b></b></p> <p><b>Results. </b>Among 1320 participants without a baseline history of LEAD, 94 (7.1%) patients developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6, 95%CI [7.8–11.7] per 1000 person-years). The LEAD incidence rate increased by worsening retinopathy: absent 5.5 (3.9–7.8), non-proliferative 14.6 (11.1–19.3), proliferative 20.1 (11.1–36.3) per 1000 person-years. Compared with absent retinopathy, non-proliferative (multi-adjusted HR 2.31, 95%CI [1.43–3.81], p=0.0006) and proliferative retinopathy (3.14 [1.40–6.15], p=0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced c-statistic (+0.023 [0.003–0.044], p=0.02), IDI (0.209 [0.130 – 0.321], p<0.001) and NRI (0.562 [0.382– 0.799], p<0.001) for LEAD risk, beyond traditional risk factors.</p> <p><b>Conclusions. </b>An independent dose-response relationship was observed between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for LEAD risk stratification, suggesting its usefulness as LEAD predictor.<b></b></p>