Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy

Context and Objective Leptin treatment has dramatic clinical effects on glucose and lipid metabolism in leptin-deficient patients with lipodystrophy. Further elucidation of metabolic effects of exogenous leptin therapy will shed light on understanding leptin physiology in humans. Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy. Study Design We conducted a pre-post treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n=10; acquired generalized lipodystrophy, n=1; familial partial lipodystrophy, n=8) who received daily subcutaneous metreleptin injections for a period of 16 - 23 weeks. A 3-hour oral glucose tolerance test and body composition measurements were conducted before and after the treatment period, and fasting blood samples were used for metabolomic profiling. The study outcome aimed at measur...