Impaired functional exercise capacity and greater cardiovascular response to the 6-min walk test in congenital generalized lipodystrophy

BACKGROUND: Congenital Generalized Lipodystrophy (CGL) is an ultra-rare disease characterized by metabolic disorders. However, the evaluation of functional exercise capacity, cardiovascular (CV) response to exercise, and peripheral arterial disease (PAD) in CGL is scarce. Here we evaluated the performance and CV response to exercise and their association with PAD in CGL compared to healthy individuals. METHODS: Twelve CGL and 12 healthy subjects matched for age and gender were included. Functional exercise capacity, CV response, and PAD were measured using the six-minute walk test (6MWT) and ankle-brachial index (ABI), respectively. RESULTS: At baseline, CGL subjects showed reduced predicted walked distance (6MWD) (p = 0.009) and increased heart rate (HR), systolic (SBP), and diastolic (DBP) pressures compared to healthy subjects (p < 0.05). Most CGL subjects presented normal ABI values (1.0 ≤ ABI ≤ 1.4). Only 25% (n = 3) had ABI ≤ 0.9. CGL subjects did not present changes in ABI and blood pressure 12 months after metreleptin (MLP) replacement, but they walked a greater 6MWD than baseline (p = 0.04). Further, 6MWD and right ABI measurements were positively correlated in CGL subjects (p = 0.03). Right ABI negatively correlated with glucose, triglycerides, and VLDL-c (p < 0.05). CONCLUSIONS: We observed that CGL subjects had lower functional exercise capacity and higher cardiovascular effort for similar performance of 6MWT, suggesting that strategies for decreasing exercise effort in this population should be essential. Furthermore, better physical performance was associated with high ABI in CGL. Additional studies are needed to clarify leptin's role in preserving functional exercise capacity in CGL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-02828-x.