Medical Care
Successful treatment of acanthosis nigricans (AN) in association with generalized lipodystrophy was accomplished in 1 patient with etretinate beginning at 75 mg/d. [21] Therapy for AN was undertaken in this patient for cosmetic reasons. After 4 weeks, the cutaneous eruption had disappeared, with only modest elevation of the preexisting hyperlipemia.
Substitution of eucaloric medium-chain triglycerides for long-chain fatty acids in the diet of 1 patient led to improvement of chylomicronemia, xanthomatosis, hypertriglyceridemia, hepatomegaly, carbohydrate tolerance, and hyperinsulinemia, but not lipoatrophy. Dietary fish oil also may be useful in improving AN.
Because conventional lipid-lowering and antihyperglycemic medications may be insufficient to control severe metabolic abnormalities, leptin has been used for severe lipodystrophy and found to significantly improve metabolic abnormalities. [22] This new option for therapy is leptin, an adipocyte hormone, which may improve insulin resistance, hyperglycemia, dyslipidemia, and hepatic steatosis. [23] Leptin is the first of a group of adipocyte-secreted hormones to be used clinically. [24] Its long-term efficacy in 15 patients with generalized lipodystrophy was evaluated. [25]
Leptin has been judged the first novel, effective, long-term treatment for severe forms of lipodystrophy. Treating severe lipodystrophy as a leptin deficiency syndrome has been shown to improve the metabolic outcomes in those affected patients. [26]
In February 2014, the FDA approved metreleptin (Myalept), a recombinant leptin analog, for congenital or acquired generalized lipodystrophy in children and adults. [27] The approval was based on results from an NIH open-label, single-arm study that included 48 patients with congenital or acquired generalized lipodystrophy who also had diabetes mellitus, hypertriglyceridemia, and/or elevated levels of fasting insulin. The trial showed reductions in fasting glucose and triglycerides. [17]
Metreleptin is not indicated for the following:
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Treatment of complications of partial lipodystrophy
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Treatment of liver disease, including nonalcoholic steatohepatitis (NASH)
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HIV-related lipodystrophy
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Use in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy
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Congenital generalized lipoatrophy in a 16-year-old girl. In T1-weighted magnetic resonance imaging (MRI) scan, transverse sections of the torso at the fifth lumbar vertebra demonstrate markedly deficient subcutaneous and visceral fat (top left). Transverse sections of the midthigh demonstrate an absence of subcutaneous fat, deep fat, intrafascicular fat, and marrow fat (bottom left); note light-colored, lipid-filled muscle tissue. Note absence of fat throughout the body (right).