Effects of leptin replacement therapy on pancreatic β-cell function in patients with lipodystrophy.
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.
Corresponding author: Phillip Gorden, phillipg@intra.niddk.nih.gov.
Ranganath
R
Muniyappa
Rebecca J
RJ
Brown
Andrea
A
Mari
Jalaja
J
Joseph
Mary A
MA
Warren
Elaine K
EK
Cochran
Monica C
MC
Skarulis
Phillip
P
Gorden
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005951:Glucose Tolerance Test; D020249:Hormone Replacement Therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology*; D020738:Leptin / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D007328:Insulin; D020738:Leptin