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

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.

• Authors: Ranganath Muniyappa, Rebecca J Brown, Andrea Mari, Jalaja Joseph, Mary A Warren, Elaine K Cochran, Monica C Skarulis, Phillip Gorden
• Journal: Diabetes care (Diabetes Care) Vol. 37 Issue 4 Pg. 1101-7 (Apr 2014) ISSN: 1935-5548 [Electronic] United States
• PMID: 24496806 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Insulin
• Leptin

Topics

• Adolescent
• Adult
• Child
• Female
• Glucose Tolerance Test
• Hormone Replacement Therapy
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Insulin Secretion
• Islets of Langerhans (drug effects, physiopathology)
• Leptin (therapeutic use)
• Lipodystrophy (drug therapy, physiopathology)
• Male
• Middle Aged
• Young Adult