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.