Efficacy of leptin therapy in the different forms of human lipodystrophy.
OBJECTIVE
Lipodystrophy is a rare disorder characterised by loss of adipose tissue, hypoleptinaemia, severe insulin resistance, diabetes and dyslipidaemia. The aims of this study were to determine whether leptin replacement in lipodystrophy patients ameliorates their metabolic abnormalities over an extended period of time and whether leptin therapy is effective in the different forms of lipodystrophy.


METHODS
We conducted an open-label prospective study of patients with acquired forms of lipodystrophy and inherited forms of lipodystrophy secondary to mutations in the AGPAT2, SEIPIN (also known as BSCL2), LMNA and PPARgamma (also known as PPARG) genes. Between July 2000 and November 2008, 48 patients with lipodystrophy were treated with s.c. recombinant methionyl human leptin.


RESULTS
Serum triacylglycerol and HbA(1c) levels declined dramatically with leptin therapy. Among 35 patients with data at baseline and 12 months, serum triacylglycerol fell by 59% (from 10.18 +/- 2.67 mmol/l to 4.16 +/- 0.99 mmol/l [means +/- SE]; p = 0.008) and HbA(1c) decreased by 1.5 percentage points (from 8.4 +/- 0.3% to 6.9 +/- 0.3%; p < 0.001). A significant reduction was seen in total cholesterol and a trend towards reduction was observed in LDL-cholesterol at 12 months. HDL-cholesterol was unchanged. Among generalised lipodystrophy patients, proteinuria diminished with leptin replacement. Patients with both acquired and inherited forms of lipodystrophy experienced decreases in serum triacylglycerol and HbA(1c) levels.


CONCLUSIONS
Leptin replacement in lipodystrophy patients leads to significant and sustained improvements in glycaemic control and dyslipidaemia. Leptin is effective in the various forms of lipodystrophy, whether they are acquired or inherited, generalised or partial.


BACKGROUND
ClinicalTrials.gov ID NCT00025883


BACKGROUND
This work was supported by intramural research funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH).
Chong
A Y
AY
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lupsa
B C
BC
Cochran
E K
EK
Gorden
P
P
D000273:Adipose Tissue / Q000033:anatomy & histology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002784:Cholesterol / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011507:Proteinuria; D011994:Recombinant Proteins / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D002784:Cholesterol; D006442:Glycated Hemoglobin; D020738:Leptin; D011994:Recombinant Proteins; D014280:Triglycerides