Clinical and metabolic characteristics of Acquired partial lipodystrophy: insights from a multicenter study

Abstract

Acquired partial lipodystrophy (APL) is characterized by loss of subcutaneous adipose tissue, primarily affecting the upper body. We aim to characterize the clinical and metabolic profiles of patients with APL and explore whether variations in clinical presentation and adipose tissue distribution are associated with the development and severity of metabolic disease. Materials and Methods This multicenter study included 36 patients with APL (median age: 38, 24–49; 25th –75th percentiles; 12 males, 24 females). For comparison, 37 patients with familial partial lipodystrophy type 2 (FPLD2) due to typical codon 482 LMNA variants (median age: 42, 32–56, 25th –75th percentiles 10 males, 27 females) were included. The median follow-up duration was 60 months (7.5–102, 25th –75th percentiles). Results Low complement 3 levels were detected in 18 of 34 patients with available assessment (52.9%). Autoimmune disorders were common, affecting 14 patients (38.9%). Metabolic abnormalities were variably observed among patients with APL, with diabetes documented in 17 patients (47.2%), hypertriglyceridemia in 21 patients (58.3%), and hepatic steatosis in 22 patients (61.1%). Chronic kidney disease developed in 19 patients (52.8%), pancreatitis in 3 (8.3%), and polycystic ovaries in 8 (42.1%) of reproductive-age women. A subgroup of patients with APL (n = 11, 30.6%) had reduced gluteofemoral adipose tissue and exhibited more severe metabolic abnormalities than those with fully preserved adipose tissue in these regions. All patients in this subgroup had diabetes; 7 of 11 had triglyceride levels > 500 mg/dL, and hepatic steatosis was present in 10 of 11. Kaplan–Meier estimates indicated earlier onset of diabetes (p < 0.001) and hypertriglyceridemia (p = 0.005) in this subgroup. Conclusions Patients with APL show a heterogeneous clinical profile, and our observations reveal a phenotypic overlap with more generalized adipose tissue loss in some patients diagnosed as APL under current classifications. In this subset, reduced gluteofemoral fat is linked to earlier onset and greater severity of metabolic complications, highlighting the importance of fat distribution in metabolically protective regions.