1018-P: Chronic Limb-Threatening Ischemia in Individuals with Type 1 Diabetes: The Impact of Diabetic Nephropathy and Severe Diabetic Retinopathy

The aim was to explore the prevalence and incidence of chronic limb threatening ischemia (CLTI) in individuals with type 1 diabetes (T1D) and to assess risk factors, especially the independent and joint association of diabetic nephropathy (DN) and severe diabetic retinopathy (SDR). The study population comprised 4,694 individuals with T1D from the nationwide Finnish Diabetic Nephropathy Study (FinnDiane). CLTI events were ascertained from medical records. There were 319 events of CLTI; 102 at baseline visit and 217 during follow-up of 11.9 (IQR 9.3-13.8) years. End-stage renal disease (ESRD) increased the risk of CLTI 12.3-fold (95% CI 5.2-28.9) compared to normoalbuminuria at baseline. Odds ratio (OR) for micro- and macroalbuminuria was 1.2 (0.4-3.6) and 2.9 (1.2-7.1), respectively. SDR increased the risk with an OR of 3.4 (1.4-8.6). Other risk factors were age, duration of diabetes, lower HDL cholesterol and estimated glucose disposal rate. The 15-year cumulative incidence of CLTI was 5.8% (5.0-6.5). Risk factors included DN, SDR, age, duration of diabetes, HbA1c, SBP, triglycerides and smoking. Hazard ratios (HRs) by combinations of DN status and with (+) or without (-) SDR were 4.1 (1.6-10.1) for normo/SDR+, 3.5 (1.3-9.6) for micro/SDR-, 10.4 (4.8-22.6) for micro/SDR+, 8.2 (3.2-21.2) for macro/SDR-, 14.3 (6.8-30.2) for macro/SDR+ and 32.6 (15.1-70.4) for ESRD compared to normo/SDR-. The 15-year risk of coronary artery disease and stroke after the diagnosis of CLTI was 48.1% (41.0-55.0) and 24.4% (19.1-30.1), respectively. Median survival time after CLTI was 5.7 (4.3-7.1) years. In conclusion, there was a graded association between the combined effect of DN and SDR on the risk of CLTI, especially strong in individuals with ESRD. Early interventions to prevent severe forms of DN and diabetic retinopathy may help to decrease the risk of CLTI in individuals with T1D. In such individuals early detection and treatment of foot ulcers is mandatory. Disclosure V. Harjutsalo: None. M. Kallio: None. C. Forsblom: None. P. Groop: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Mundipharma International. The finndiane study group: n/a. Funding Folkhalsan Research Foundation Academy of Finland (299200, 316664); Wilhelm and Else Stockmann Foundation; Liv och Halsa Society; Novo Nordisk Foundation (NNF OC0013659); Finnish Foundation for Cardiovascular Research; Diabetes Research Foundation