Cited by 83Adipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and ObesityGrowth Hormone and Insulin-like Growth Factors

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

Cochran, Elaine, Young, Janice Ryan, Sebring, Nancy, DePaoli, Alex, Oral, Elif Arioglu, Gorden, Phillip·2004·The Journal of Clinical Endocrinology & Metabolism

Abstract

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.

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Crossref · 10.1210/jc.2003-031952

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  • Patients with extreme insulin resistance as a result of receptor mutations or autoantibodies do not have NASH-associated findings such as hypertriglyceridemia, hepatomegaly, or abnormal liver function tests.

    “In our experience, patients with extreme insulin resistance as a result of receptor mutations 17,18 or autoantibodies 19 do not have NASH-associated findings such as hypertriglyceridemia, hepatomegaly, or abnormal liver function tests.”

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Authors
Cochran, E., Young, J. R., Sebring, N., DePaoli, A., Oral, E. A., & Gorden, P.
Affiliations
  • National Institutes of Health (US)
  • National Institute of Diabetes and Digestive and Kidney Diseases (US)
  • Amgen (United States) (US)
  • University of Michigan (US)
Corresponding author
Cochran, Elaine
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2004-04
Volume
89
Issue
4
Pages
1548-1554
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W1999224669
Cited by
83
References
18
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 3
FWCI
5.75
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • NIH Clinical Center
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
Rabson-Mendenhall syndrome, insulin resistance, insulin receptor mutations, acanthosis nigricans, type 2 diabetes, insulin tolerance, HbA1c, leptin therapy, pediatric patients
MeSH terms
Adolescent, Blood Glucose, Child, Child Development, Fasting, Female, Glucose Tolerance Test, Growth, Glycated Hemoglobin, Humans, Hypothalamo-Hypophyseal System, Insulin, Insulin Resistance, Male, Pilot Projects, Syndrome, Leptin, Adolescent Development

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