title: Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety.
abstract: BACKGROUND
  Leptin replacement therapy improves metabolic complications in patients with lipodystrophy and severe hypoleptinemia (SH), but whether the response is related to the degree of hypoleptinemia remains unclear.
  
  
  OBJECTIVE
  The aim of the study was to compare efficacy of leptin therapy in familial partial lipodystrophy, Dunnigan variety (FPLD) patients with SH (serum leptin<7th percentile of normal) vs. those with moderate hypoleptinemia (MH; serum leptin in 7th to 20th percentiles).
  
  
  METHODS
  We conducted an open-label, parallel group, observational study in 14 SH (mean±sd, serum leptin, 1.9±1.1 ng/ml) and 10 MH (serum leptin, 5.3±1.0 ng/ml) women with FPLD.
  
  
  METHODS
  Patients received 0.08 mg/kg·d of metreleptin by twice daily sc injections for 6 months.
  
  
  METHODS
  The primary outcome variable was change in fasting serum triglycerides. Other secondary variables were fasting plasma glucose and insulin, insulin sensitivity, hemoglobin A1c, and hepatic triglyceride content.
  
  
  RESULTS
  Median fasting serum triglycerides decreased from 228 to 183 mg/dl in the SH group (P=0.04) and from 423 to 339 mg/dl in the MH group (P=0.02), but with no difference between the groups (P value for interaction=0.96). Hepatic triglyceride levels similarly declined significantly from 8.8 to 4.9% in the SH group and from 23.7 to 9.2% in the MH group (P value for interaction=0.9). Loss of body weight and body fat occurred in both groups. Fasting glucose, insulin, glucose tolerance, and hemoglobin A1c levels did not change. K value on insulin tolerance test improved slightly in the SH group (0.98 to 1.24%; P=0.01), but not in the MH group (1.1 to 1.27%; P=0.4).
  
  
  CONCLUSIONS
  Metreleptin replacement therapy is equally effective in FPLD patients with both SH and MH in reducing serum and hepatic triglyceride levels, but did not improve hyperglycemia.
authors.affiliation: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, K5.214, Dallas, Texas 75390-8537, USA.
authors.forename: Vinaya
authors.initials: V
authors.lastname: Simha
authors.forename: Lalitha
authors.initials: L
authors.lastname: Subramanyam
authors.forename: Lidia
authors.initials: L
authors.lastname: Szczepaniak
authors.forename: Claudia
authors.initials: C
authors.lastname: Quittner
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.forename: Peter
authors.initials: P
authors.lastname: Snell
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D052496:Lipodystrophy, Familial Partial / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; C415771:metreleptin