Efficacy of Recombinant Methionyl Human Leptin Therapy for the Extreme Insulin Resistance of the Rabson-Mendenhall Syndrome (original) (raw)

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1Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (E.C., J.R.Y., E.A.O., P.G.), Bethesda, Maryland 20892

*Address all correspondence and requests for reprints to: Elaine Cochran, CRNP, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 8D20, Bethesda, Maryland 20892.

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1Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (E.C., J.R.Y., E.A.O., P.G.), Bethesda, Maryland 20892

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2Clinical Center Nutrition Department (N.S.), National Institutes of Health, Bethesda, Maryland 20892

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3Amgen, Inc. (A.D.), Thousand Oaks, California 91320

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1Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (E.C., J.R.Y., E.A.O., P.G.), Bethesda, Maryland 20892

4Department of Medicine, Division of Endocrinology, University of Michigan (E.A.O.), Ann Arbor, Michigan 48109

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1Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (E.C., J.R.Y., E.A.O., P.G.), Bethesda, Maryland 20892

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Received:

11 November 2003

Accepted:

15 January 2004

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Elaine Cochran, Janice Ryan Young, Nancy Sebring, Alex DePaoli, Elif Arioglu Oral, Phillip Gorden, Efficacy of Recombinant Methionyl Human Leptin Therapy for the Extreme Insulin Resistance of the Rabson-Mendenhall Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 89, Issue 4, 1 April 2004, Pages 1548–1554, https://doi.org/10.1210/jc.2003-031952
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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.

Copyright © 2004 by The Endocrine Society

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