Diabetic retinopathy (DR) has been linked to lower-extremity artery disease (LEAD), but there remains some uncertainty as whether this association is mediated by other conditions. We assessed the association between DR and LEAD risk; and the influence of diabetes duration and control, systolic (SBP) or diastolic (DBP) blood pressure, smoking, diabetic kidney disease (DKD), or cardiovascular disease (CVD) in such association in the French prospective SURDIAGENE (SURVIe, DIAbete de type 2 et GENEtique) type 2 diabetes cohort. Baseline DR was staged as absent, non-proliferative, or proliferative. Major LEAD was defined as lower-limb amputation or peripheral revascularization requirement. Cox regression model was fitted to compute hazard ratio (HR) and 95% CI for major LEAD during follow-up by baseline DR stages. The prognostic value of DR in LEAD discrimination was tested using C-statistics. Among 1412 participants at baseline (men 58%, age 64.7±10.6 years, non-proliferative 37% and proliferative DR 7%), 112 (7.9%) developed a major LEAD during 6 years of follow-up. The incidence of LEAD increased with worsening DR: 4.1% (absent), 12.6% (non-proliferative), and 14.1% (proliferative)(p<0.0001). This association remained significant after adjustment for confounding variables (non-proliferative versus absent DR 2.29 [1.44-3.63], p<0.0001; proliferative versus absent DR 3.03 [1.54-5.96], p=0.001). No heterogeneity was observed across subgroups by diabetes duration, HbA1c, SBP, DBP, smoking, DKD, and CVD (all p-interaction>0.05). In addition to usual risk factors, DR improved LEAD discrimination (C-statistics change +0.023 [0.004-0.038], p=0.01). LEAD risk increases proportionally with DR severity, independently of diabetic, blood pressure, renal or cardiovascular conditions. DR has a significant prognostic value in LEAD prediction in people with type 2 diabetes.

Disclosure

N. Foussard: None. P. Saulnier: None. C. Bertrand: None. E. Gand: None. S. Ragot: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi. G. Velho: None. M. Marre: Advisory Panel; Self; Servier. Board Member; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. V. Rigalleau: None. K. Mohammedi: None. S. Hadjadj: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Servier. Research Support; Self; Bayer AG, Janssen Research & Development. Speaker's Bureau; Self; Abbott, Valbiotis.

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