Effects of Leptin Replacement Therapy on Pancreatic β-Cell Function in Patients With Lipodystrophy

Abstract

OBJECTIVELeptin 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 METHODSIn 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.RESULTSThere 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.CONCLUSIONSIn 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.