Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson‐Mendenhall syndrome
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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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.”
From Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy† (2005) · cites this paper as [17]
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Brown, R. J., & Lightbourne, M. (2026) · Contemporary Endocrinology · doi:10.1007/978-3-032-17036-1_12
Hung, A., Wang, X., Gao, M., Ng, M., Oliinyk, D., Weaver, R. R., Zollbrecht, E., Cardoso, S. C., Ronel, G. S., Paolucci, C. A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.04.722722
Lipodystrophy: The experiment of nature to study leptin
Ahima, R. S., & Jackson, M. B. (2006) · Springer eBooks · doi:10.1007/978-0-387-31416-7_12
- 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
- Publisher
- The Endocrine Society
- 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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