title: Metreleptin improves blood glucose in patients with insulin receptor mutations.
abstract: BACKGROUND
  Rabson-Mendenhall syndrome (RMS) is caused by mutations of the insulin receptor and results in extreme insulin resistance and dysglycemia. Hyperglycemia in RMS is very difficult to treat, and patients are at risk for early morbidity and mortality from complications of diabetes.
  
  
  OBJECTIVE
  Our objective was to study 1-year effects of recombinant human methionyl leptin (metreleptin) in 5 patients with RMS and 10-year effects in 2 of these patients.
  
  
  METHODS
  We conducted an open-label nonrandomized study at the National Institutes of Health.
  
  
  METHODS
  Patients were adolescents with RMS and poorly controlled diabetes.
  
  
  METHODS
  Two patients were treated with escalating doses (0.02 up to 0.22 mg/kg/d) of metreleptin for 10 years, including 3 cycles of metreleptin withdrawal and reinitiation. In all 5 patients, 1-year effects of metreleptin (0.22 mg/kg/d) were studied.
  
  
  METHODS
  Hemoglobin A1c (HbA1c) and body mass index (BMI) z-scores were evaluated every 6 months.
  
  
  RESULTS
  HbA1c decreased from 11.4% ± 1.1% at baseline to 9.3% ± 1.9% after 6 months and 9.7% ± 1.6% after 12 months of metreleptin (P = .007). In patients treated for 10 years, HbA1c declined with each cycle of metreleptin and rose with each withdrawal. BMI z-scores declined from -1.4 ± 1.8 at baseline, to -2.6 ± 1.6 after 12 months of metreleptin (P = .0006). Changes in BMI z-score correlated with changes in HbA1c (P < .0001).
  
  
  CONCLUSIONS
  Metreleptin treatment for 12 months was associated with a 1.7% reduction in HbA1c; part of this improvement was likely mediated via decreased BMI. Metreleptin is a promising treatment option for RMS, but additional therapies are needed to achieve HbA1c targets.
authors: MD, MHSc, Building 10-CRC, Room 6-5942, 10 Center Drive, Bethesda, Maryland 20892. brownrebecca@mail.nih.gov.
authors: Rebecca J
authors: RJ
authors: Brown
authors: Elaine
authors: E
authors: Cochran
authors: Phillip
authors: P
authors: Gorden
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D056731:Donohue Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D020738:Leptin; D011972:Receptor, Insulin; C517652:hemoglobin A1c protein, human; C415771:metreleptin
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