The impact of diabetic nephropathy and severe diabetic retinopathy on chronic limb threatening ischemia risk in individuals with type 1 diabetes: a nationwide, population study

BACKGROUND: The prevalence, incidence and risk factors and especially the effect of diabetic nephropathy (DN) and diabetic retinopathy on the risk of chronic limb threatening ischemia (CLTI) have been sparsely studied in individuals with type 1 diabetes (T1D). METHODS: The prospective cohort study consisted of 4697 individuals with T1D from the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. Medical records were thoroughly reviewed in order to ascertain all CLTI events. The key risk factors were DN and severe diabetic retinopathy (SDR). FINDINGS: There were 319 events of confirmed CLTI, 102 prevalent events at baseline and 217 incident events during the follow-up of 11.9 (IQR 9.3–13.8) years. The 12-year cumulative incidence of CLTI was 4.6% (95% CI 4.0–5.3). Risk factors included presence of DN, SDR, age, duration of diabetes, HbA(1c), systolic blood pressure, triglycerides and current smoking. Sub-hazard ratios (SHRs) according to combinations of DN status and presence (+) or absence (−) of SDR were 4.8 (2.0–11.7) for normoalbuminuria/SDR+, 3.2 (1.1–9.4) for microalbuminuria/SDR−, 11.9 (5.4–26.5) for microalbuminuria/SDR+, 8.7 (3.2–23.2) for macroalbuminuria/SDR−, 15.6 (7.4–33.0) for macroalbuminuria/SDR+ and 37.9 (17.2–78.9) for kidney failure compared with individuals with normal albumin excretion rate and without SDR. INTERPRETATION: Diabetic nephropathy, especially kidney failure, is associated with high risk of limb threatening ischemia in individuals with T1D. The risk of CLTI increases gradually according to the severity of diabetic nephropathy. Also, diabetic retinopathy is independently and additively associated with high risk of CLTI. FUNDING: This research was funded by grants from 10.13039/100015736Folkhälsan Research Foundation, Academy of Finland (316664), 10.13039/100010113Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, 10.13039/501100009708Novo Nordisk Foundation (NNF OC0013659), 10.13039/501100005633Finnish Foundation for Cardiovascular Research, 10.13039/501100013500Finnish Diabetes Research Foundation, Medical Society of Finland, 10.13039/501100006306Sigrid Jusélius Foundation and Helsinki University Hospital Research Funds.