Abstract
BACKGROUND: To develop a 10-year risk score to predict lower-limb amputation (LLA) in individuals with type 1 diabetes, and to assess whether this score also predicts kidney failure, and cardiovascular disease (CVD). METHODS: The LLA risk score was derived from GENEDIAB and GENESIS, two prospective French and Belgian cohorts of 828 individuals with type 1 diabetes. External validation was assessed in SURGENE, an independent cohort of 247 individuals with type 1 diabetes. LLA was defined as a non-traumatic amputation above the metatarsophalangeal joint, kidney failure as the need for renal replacement therapy, transplantation, or an estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m(2), CVD as the occurrence of myocardial infarction, heart failure, or stroke, and major adverse cardiac event (MACE) as a composite of myocardial infarction, stroke, heart failure, or all-cause death. RESULTS: During 12 years of follow-up, LLA, kidney failure, CVD and MACE occurred in 71 (9%), 84 (11%), 138 (17%) and 265 (32.0%) of participants, respectively. Sex, diabetes duration, prior LLA, eGFR, and albuminuria were identified as independent determinants of incident LLA and were used to construct the risk score. Compared to participants in the lowest score, those in the highest score had a significantly increased risks of LLA (multivariable-adjusted HR 6.02 [95% CI, 1.92-18.89]), kidney failure (8.97 [3.95-20.37]), CVD (2.50 [1.34-4.64]) and MACE (1.91 [1.24-2.96]). The score demonstrated good discriminative performance for LLA (C-index 0.82 [0.77-0.87]), kidney failure (0.86 [0.82-0.91]), CVD (0.73 [0.68-0.78]), and MACE (0.71 [0.68-0.75]). Similar predictive performance was observed in the validation cohort. CONCLUSION: This newly developed 10-year LLA risk score achieved excellent ability to identify individuals with type 1 diabetes at high risk for LLA, kidney failure, CVD, and MACE.