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.

Impairment of respiratory muscle strength in Berardinelli-Seip congenital lipodystrophy subjects.

BACKGROUND: Berardinelli-Seip Congenital Generalized Lipodystrophy (BSCL) is an ultra-rare metabolic disease characterized by hypertriglyceridemia, hyperinsulinemia, hyperglycemia, hypoleptinemia, and diabetes mellitus. Although cardiovascular disturbances have been observed in BSCL patients, there are no studies regarding the Respiratory Muscle Strength (RMS) in this type of lipodystrophy. This study aimed to evaluate RMS in BSCL subjects compared with healthy subjects. METHODS: Eleven individuals with BSCL and 11 healthy subjects matched for age and gender were included in this study. The Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), and Peripheral Muscle Strength (PMS) were measured for three consecutive years. BSCL subjects were compared to healthy individuals for MIP, MEP, and PMS. Correlations between PMS and MIP were also analyzed. The genetic diagnosis was performed, and sociodemographic and anthropometric data were also collected. RESULTS: BSCL subjects showed significantly lower values for MIP and MEP (p <  0.0001 and p = 0.0002, respectively) in comparison to healthy subjects, but no changes in handgrip strength (p = 0.15). Additionally, we did not observe changes in MIP, MEP, and PMS two years after the first analysis, showing maintenance of respiratory dysfunction in BSCL subjects (p = 0.05; p = 0.45; p = 0.99). PMS and MIP were not correlated in these subjects (r = 0.56; p = 0.18). CONCLUSION: BSCL subjects showed lower respiratory muscle strength when compared with healthy subjects; however, PMS was not altered. These findings were maintained at similar levels during the two years of evaluation. Our data reveal the first association of BSCL with the development of respiratory muscle weakness.