Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome

J Clin Endocrinol Metab. 2004 Apr;89(4):1548-54. doi: 10.1210/jc.2003-031952.


Recombinant methionyl human leptin (r-metHuLeptin) therapy has shown clear efficacy in the treatment of severe insulin resistance associated with lipodystrophy syndromes and low leptin levels. We treated two siblings with Rabson-Mendenhall syndrome (severe insulin resistance and presumed insulin receptor mutations). The brother and sister, aged 13 and 11 yr, respectively, had severe acanthosis nigricans, insulin resistance, and diabetes. Both were taking 2000 mg metformin and 2 mg rosiglitazone daily; the brother was also taking 300 U regular insulin daily. In contrast to our lipoatrophic patients treated with r-metHuLeptin, these two patients had a higher percent body fat and low-normal fasting triglycerides [42 mg/dl (0.37 mmol/liter), male sibling, and 33 mg/dl (0.47 mmol/liter), female sibling]. The siblings were treated with r-metHuLeptin therapy for 10 months and demonstrated a 40-60% decrease in fasting serum glucose and insulin levels and improved glycosylated hemoglobin. There was corresponding improvement in glucose and insulin tolerance during leptin therapy. This is the first report of a partial, but significant, effect of r-metHuLeptin administration in patients with extreme insulin resistance with a presumed insulin receptor mutation and low serum triglyceride levels.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adolescent Development / drug effects
  • Blood Glucose / analysis
  • Child
  • Child Development / drug effects
  • Fasting / blood
  • Female
  • Glucose Tolerance Test
  • Glycated Hemoglobin A / metabolism
  • Growth / drug effects
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology
  • Insulin / blood
  • Insulin Resistance*
  • Leptin / analogs & derivatives*
  • Leptin / therapeutic use*
  • Male
  • Pilot Projects
  • Syndrome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Leptin
  • recombinant methionyl human leptin