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Effects of leptin replacement therapy on pancreatic ?-cell function in patients with lipodystrophy.


ABSTRACT: OBJECTIVE Leptin administration is known to directly modulate pancreatic ?-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on ?-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on ?-cell function in patients with lipodystrophy. RESEARCH DESIGN AND METHODS In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on ?-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. ?-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT. RESULTS There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, ?-cell glucose sensitivity, rate sensitivity, or insulin clearance. CONCLUSIONS In contrast to the suppressive effects of leptin on ?-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or ?-cell function in leptin-deficient individuals with lipodystrophy.

SUBMITTER: Muniyappa R 

PROVIDER: S-EPMC3964492 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Effects of leptin replacement therapy on pancreatic β-cell function in patients with lipodystrophy.

Muniyappa Ranganath R   Brown Rebecca J RJ   Mari Andrea A   Joseph Jalaja J   Warren Mary A MA   Cochran Elaine K EK   Skarulis Monica C MC   Gorden Phillip P  

Diabetes care 20140204 4


OBJECTIVE Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy. RESEARCH DESIGN AND METHODS In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on β-cell function i  ...[more]

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