title: Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience.
abstract: Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.
authors.affiliation: Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain, david.araujo@usc.es.
authors.forename: David
authors.initials: D
authors.lastname: Araujo-Vilar
authors.forename: Sofía
authors.initials: S
authors.lastname: Sánchez-Iglesias
authors.forename: Cristina
authors.initials: C
authors.lastname: Guillín-Amarelle
authors.forename: Ana
authors.initials: A
authors.lastname: Castro
authors.forename: Mary
authors.initials: M
authors.lastname: Lage
authors.forename: Marcos
authors.initials: M
authors.lastname: Pazos
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rial
authors.forename: Javier
authors.initials: J
authors.lastname: Blasco
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.forename: Rosario
authors.initials: R
authors.lastname: Domingo-Jiménez
authors.forename: María Ruiz
authors.initials: MR
authors.lastname: del Campo
authors.forename: Blanca
authors.initials: B
authors.lastname: González-Méndez
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000209:etiology; D020738:Leptin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D052497:Lipodystrophy, Congenital Generalized / Q000150:complications / Q000188:drug therapy*; D052496:Lipodystrophy, Familial Partial / Q000150:complications / Q000188:drug therapy*; D008297:Male; D013030:Spain; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020738:Leptin; C415771:metreleptin