Leptin-replacement therapy for lipodystrophy

Elif Arioglu Oral, Vinaya Simha, Elaine Ruiz, Alexa Andewelt, Ahalya Premkumar, Peter Snell, Anthony J. Wagner, Alex M. DePaoli, Marc L. Reitman, Simeon I. Taylor, Phillip Gorden, Abhimanyu Garg

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Abstract

Background: The adipocyte hormone leptin is important in regulating energy homeostasis. Since severe lipodystrophy is associated with leptin deficiency, insulin resistance, hypertriglyceridemia, and hepatic steatosis, we assessed whether leptin replacement would ameliorate this condition. Methods: Nine female patients (age range, 15 to 42 years; eight with diabetes mellitus) who had lipodystrophy and serum leptin levels of less than 4 ng per milliliter (0.32 nmol per milliliter) received recombinant methionyl human leptin (recombinant leptin). Recombinant leptin was administered subcutaneously twice a day for four months at escalating doses to achieve low, intermediate, and high physiologic replacement levels of leptin. Results: During treatment with recombinant leptin, the serum leptin level increased from a mean (±SE) of 1.3±0.3 ng per milliliter to 11.1±2.5 ng per milliliter (0.1±0.02 to 0.9±0.2 nmol per milliliter). The absolute decrease in the glycosylated hemoglobin value was 1.9 percent (95 percent confidence interval, 1.1 to 2,7 percent; P=0.001) in the eight patients with diabetes. Four months of therapy decreased average triglyceride levels by 60 percent (95 percent confidence interval, 43 to 77 percent; P<0.001) and liver volume by an average of 28 percent (95 percent confidence interval, 20 to 36 percent; P=0.002) in all nine patients and led to the discontinuation of or a large reduction in antidiabetes therapy. Self-reported daily caloric intake and the measured resting metabolic rate also decreased significantly with therapy. Over-all, recombinant leptin therapy was well tolerated. Conclusions: Leptin-replacement therapy improved glycemic control and decreased triglyceride levels in patients with lipodystrophy and leptin deficiency. Leptin deficiency contributes to the insulin resistance and other metabolic abnormalities associated with severe lipodystrophy.

Original languageEnglish (US)
Pages (from-to)570-578
Number of pages9
JournalNew England Journal of Medicine
Volume346
Issue number8
DOIs
StatePublished - Feb 21 2002

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Lipodystrophy
Leptin
Therapeutics
Confidence Intervals
Insulin Resistance
Triglycerides
Basal Metabolism
Hypertriglyceridemia
Liver
Glycosylated Hemoglobin A
Energy Intake
Serum
Adipocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., ... Garg, A. (2002). Leptin-replacement therapy for lipodystrophy. New England Journal of Medicine, 346(8), 570-578. https://doi.org/10.1056/NEJMoa012437

Leptin-replacement therapy for lipodystrophy. / Oral, Elif Arioglu; Simha, Vinaya; Ruiz, Elaine; Andewelt, Alexa; Premkumar, Ahalya; Snell, Peter; Wagner, Anthony J.; DePaoli, Alex M.; Reitman, Marc L.; Taylor, Simeon I.; Gorden, Phillip; Garg, Abhimanyu.

In: New England Journal of Medicine, Vol. 346, No. 8, 21.02.2002, p. 570-578.

Research output: Contribution to journalArticle

Oral, EA, Simha, V, Ruiz, E, Andewelt, A, Premkumar, A, Snell, P, Wagner, AJ, DePaoli, AM, Reitman, ML, Taylor, SI, Gorden, P & Garg, A 2002, 'Leptin-replacement therapy for lipodystrophy', New England Journal of Medicine, vol. 346, no. 8, pp. 570-578. https://doi.org/10.1056/NEJMoa012437
Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P et al. Leptin-replacement therapy for lipodystrophy. New England Journal of Medicine. 2002 Feb 21;346(8):570-578. https://doi.org/10.1056/NEJMoa012437
Oral, Elif Arioglu ; Simha, Vinaya ; Ruiz, Elaine ; Andewelt, Alexa ; Premkumar, Ahalya ; Snell, Peter ; Wagner, Anthony J. ; DePaoli, Alex M. ; Reitman, Marc L. ; Taylor, Simeon I. ; Gorden, Phillip ; Garg, Abhimanyu. / Leptin-replacement therapy for lipodystrophy. In: New England Journal of Medicine. 2002 ; Vol. 346, No. 8. pp. 570-578.
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AU - Oral, Elif Arioglu

AU - Simha, Vinaya

AU - Ruiz, Elaine

AU - Andewelt, Alexa

AU - Premkumar, Ahalya

AU - Snell, Peter

AU - Wagner, Anthony J.

AU - DePaoli, Alex M.

AU - Reitman, Marc L.

AU - Taylor, Simeon I.

AU - Gorden, Phillip

AU - Garg, Abhimanyu

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N2 - Background: The adipocyte hormone leptin is important in regulating energy homeostasis. Since severe lipodystrophy is associated with leptin deficiency, insulin resistance, hypertriglyceridemia, and hepatic steatosis, we assessed whether leptin replacement would ameliorate this condition. Methods: Nine female patients (age range, 15 to 42 years; eight with diabetes mellitus) who had lipodystrophy and serum leptin levels of less than 4 ng per milliliter (0.32 nmol per milliliter) received recombinant methionyl human leptin (recombinant leptin). Recombinant leptin was administered subcutaneously twice a day for four months at escalating doses to achieve low, intermediate, and high physiologic replacement levels of leptin. Results: During treatment with recombinant leptin, the serum leptin level increased from a mean (±SE) of 1.3±0.3 ng per milliliter to 11.1±2.5 ng per milliliter (0.1±0.02 to 0.9±0.2 nmol per milliliter). The absolute decrease in the glycosylated hemoglobin value was 1.9 percent (95 percent confidence interval, 1.1 to 2,7 percent; P=0.001) in the eight patients with diabetes. Four months of therapy decreased average triglyceride levels by 60 percent (95 percent confidence interval, 43 to 77 percent; P<0.001) and liver volume by an average of 28 percent (95 percent confidence interval, 20 to 36 percent; P=0.002) in all nine patients and led to the discontinuation of or a large reduction in antidiabetes therapy. Self-reported daily caloric intake and the measured resting metabolic rate also decreased significantly with therapy. Over-all, recombinant leptin therapy was well tolerated. Conclusions: Leptin-replacement therapy improved glycemic control and decreased triglyceride levels in patients with lipodystrophy and leptin deficiency. Leptin deficiency contributes to the insulin resistance and other metabolic abnormalities associated with severe lipodystrophy.

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