Leptin-replacement therapy for lipodystrophy.
BACKGROUND
The adipocyte hormone leptin is important in regulating energy homeostasis. Since severe lipodystrophy is associated with leptin deficiency, insulin resistance, hypertriglyceridemia, and hepatic steatosis, we assessed whether leptin replacement would ameliorate this condition.


METHODS
Nine female patients (age range, 15 to 42 years; eight with diabetes mellitus) who had lipodystrophy and serum leptin levels of less than 4 ng per milliliter (0.32 nmol per milliliter) received recombinant methionyl human leptin (recombinant leptin). Recombinant leptin was administered subcutaneously twice a day for four months at escalating doses to achieve low, intermediate, and high physiologic replacement levels of leptin.


RESULTS
During treatment with recombinant leptin, the serum leptin level increased from a mean (+/- SE) of 1.3 +/- 0.3 ng per milliliter to 11.1 +/- 2.5 ng per milliliter (0.1 +/- 0.02 to 0.9 +/- 0.2 nmol per milliliter). The absolute decrease in the glycosylated hemoglobin value was 1.9 percent (95 percent confidence interval, 1.1 to 2.7 percent; P=0.001) in the eight patients with diabetes. Four months of therapy decreased average triglyceride levels by 60 percent (95 percent confidence interval, 43 to 77 percent; P<0.001) and liver volume by an average of 28 percent (95 percent confidence interval, 20 to 36 percent; P=0.002) in all nine patients and led to the discontinuation of or a large reduction in antidiabetes therapy. Self-reported daily caloric intake and the measured resting metabolic rate also decreased significantly with therapy. Overall, recombinant leptin therapy was well tolerated.


CONCLUSIONS
Leptin-replacement therapy improved glycemic control and decreased triglyceride levels in patients with lipodystrophy and leptin deficiency. Leptin deficiency contributes to the insulin resistance and other metabolic abnormalities associated with severe lipodystrophy.
Oral
Elif Arioglu
EA
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1770, USA. elif_arioglu@nih.gov
Simha
Vinaya
V
Ruiz
Elaine
E
Andewelt
Alexa
A
Premkumar
Ahalya
A
Snell
Peter
P
Wagner
Anthony J
AJ
DePaoli
Alex M
AM
Reitman
Marc L
ML
Taylor
Simeon I
SI
Gorden
Phillip
P
Garg
Abhimanyu
A
D000293:Adolescent; D000328:Adult; D001481:Basal Metabolism / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D007333:Insulin Resistance; D020738:Leptin / Q000008:administration & dosage / Q000009:adverse effects / Q000172:deficiency / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000150:complications / Q000151:congenital / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D020738:Leptin; D014280:Triglycerides