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Aim  Patients with lipodystrophy are at high risk for chronic complications of diabetes. Recently, we have reported 18 diabetic foot ulcer episodes in 9 subjects with lipodystrophy. This current study aims to determine risk factors associated with foot ulcer development in this rare disease population.    Methods  Ninety metreleptin naïve patients with diabetes registered in our national lipodystrophy database were included in this observational retrospective cohort study (9 with and 81 without foot ulcers).    Results  Patients with lipodystrophy developing foot ulcers had longer diabetes duration ( p  = 0.007), longer time since lipodystrophy diagnosis ( p  = 0.008), and higher HbA1c levels ( p  = 0.041). Insulin use was more prevalent ( p  = 0.003). The time from diagnosis of diabetes to first foot ulcer was shorter for patients with generalized lipodystrophy compared to partial lipodystrophy ( p  = 0.036). Retinopathy ( p  < 0.001), neuropathy ( p  < 0.001), peripheral artery disease ( p  = 0.001), and kidney failure ( p  = 0.003) were more commonly detected in patients with foot ulcers. Patients with foot ulcers tended to have lower leptin levels ( p  = 0.052). Multiple logistic regression estimated significant associations between foot ulcers and generalized lipodystrophy (OR: 40.81, 95% CI: 3.31–503.93,  p  = 0.004), long-term diabetes (≥ 15 years; OR: 27.07, 95% CI: 2.97–246.39,  p  = 0.003), and decreased eGFR (OR: 13.35, 95% CI: 1.96–90.67,  p  = 0.008).    Conclusions  Our study identified several clinical factors associated with foot ulceration among patients with lipodystrophy and diabetes. Preventive measures and effective treatment of metabolic consequences of lipodystrophy are essential to prevent the occurrence of foot ulcers in these high-risk individuals.

Risk factors for diabetic foot ulcers in metreleptin naïve patients with lipodystrophy