Leptin Improves Cardiac Structure and Function in Patients With Generalized Lipodystrophy

Lipodystrophy (LD) syndromes are rare disorders of deficient adipose tissue and severe metabolic disease, including insulin resistance, diabetes, and hypertriglyceridemia. LD may affect all adipose depots (generalized LD, GLD) or only some depots (partial LD, PLD). Low adipose mass leads to very low leptin in GLD, and variable leptin in PL. Treatment with exogenous leptin (metreleptin) improves metabolic disease in LD, particularly GLD. Left ventricular (LV) hypertrophy is frequent in LD, especially GLD. The mechanism for hypertrophy in LD is not known and may relate to glucose or lipotoxicity. We hypothesized that metreleptin would improve cardiac abnormalities in LD, and that this would be mediated by improvements in glucose and triglycerides (TG). We analyzed echocardiograms (echo), blood pressure (BP), heart rate (HR), and metabolic parameters in 38 subjects with LD (18 GLD, 20 PLD) who were treated with metreleptin in open-label clinical studies at the National Institutes of Health. 27 had repeat echo after 1y of metreleptin (mean 1.0 ± 0.2y), and 23 after 3 to 5y (mean 3.7±0.6y). In GLD, metreleptin significantly improved metabolic disease, including reduced TG (median(IQR) 740(403–1239), 138(88–196), 211(136–558) mg/dL at baseline, 1y, & 3-5y, P