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

AI Article Synopsis

  • Leptin administration can influence pancreatic β-cell function, but its effects on humans with lipodystrophy had not been well studied prior to this research.
  • A study involving 13 patients with lipodystrophy examined the impacts of leptin replacement over 16-20 weeks, measuring insulin secretory rates during glucose tolerance tests.
  • Results showed that while leptin therapy reduced triglycerides and other markers, it did not significantly change insulin secretion or β-cell function in these patients.

Article Abstract

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 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. β-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, β-cell glucose sensitivity, rate sensitivity, or insulin clearance. CONCLUSIONS In contrast to the suppressive effects of leptin on β-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964492PMC
http://dx.doi.org/10.2337/dc13-2040DOI Listing

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