Lipodystrophies are rare, heterogeneous, genetic, or acquired disorders, characterized by varying degrees of body fat loss and associated metabolic complications, including insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes mellitus. Fat loss may be restricted to only small areas (localized), on the upper and lower extremities (in familial partial lipodystrophies), on the upper half of the body including the face, neck, upper extremities, chest and sometimes abdomen (acquired partial lipodystrophy), or all over the body (generalized lipodystrophies).
For treatment of metabolic complications, such as diabetes mellitus and hyperlipidemia, conventional medications are used. In the author’s experience, management of hyperglycemia in some patients requires high doses of insulin and concentrated insulin preparations, such as U300 or U500 insulins. For hypertriglyceridemia, fibric acid derivatives, fenofibrate or gemfibrozil, as well as long-chain omega-3 polyunsaturated fatty acids from fish oils are used. Metreleptin therapy in the United States is approved only for patients with congenital generalized lipodystrophy (CGL) or acquired generalized lipodystrophy (AGL). In the author’s experience, patients with CGL or AGL who have uncontrolled diabetes, hyperlipidemia, or hepatic steatosis are likely to benefit from metreleptin therapy. Whether young children or infants with CGL or AGL should be treated with metreleptin to prevent development of metabolic complications is not clear. Furthermore, whether metreleptin can change the natural course of disease progression among patients with CGL and AGL, also remains unclear. In other countries such as in Japan and Europe, metreleptin is also approved for patients with partial lipodystrophies in poor metabolic control.
Patients with lipodystrophies also undergo various cosmetic procedures to improve physical appearance, including autologous fat transplantation, dermal fillers, muscle transplantation, liposuction for excess fat accumulation in nonlipodystrophic regions, and breast augmentation. See Table 64-1.
Table 64-1Lipodystrophies Treatment Table ||Download (.pdf) Table 64-1 Lipodystrophies Treatment Table
|MEDICATION NAME ||INDICATION ||MECHANISM OF ACTION ||DOSING ||ADVERSE EFFECTS ||SUGGESTED MONITORING ||LEVEL OF EVIDENCE (REFERENCE) |
|Systemic Therapy |
|Metreleptin ||Generalized lipodystrophya,b || |
Central reduction of excessive appetite.
Improvement of peripheral insulin resistance
|0.04-0.08 mg/kg/d in males and 0.08-0.12 mg/kg/d in females subcutaneously daily ||Local injection site reactions, development of neutralizing antibodies, rare cases of lymphomas ||Glycemic and lipid parameters every 3-6 mo ||IIA1-8 |
|Insulin (U100-U500) ||Diabetes mellitus ||Reduction of hepatic glucose output and enhanced peripheral glucose disposal ||Variable, based on blood glucose levels ||Hypoglycemia, localized lipohypertrophy ||Glycemic parameters every 3 mo ||IV8 |
|Fibrates ||Hypertriglyceridemia ||PPAR alpha agonists || |
Gemfibrozil 600 mg twice daily
Fenofibrate 200 mg daily
|Myopathy, gallstones, elevation of serum creatinine ||Lipid parameters every 3 mo ||IV8 |
|Fish oils ||Hypertriglyceridemia ||Competitive inhibition of hepatic triglyceride synthesis ||2 g twice daily or more ||Nausea, diarrhea, bleeding tendency ||Lipid parameters every 3 mo ||IV8 |
|Procedural Therapy |
|Autologous fat transplantation ||Localized, APL, LD-HIV ||NA ||NA ||Bruising ||As needed ||IV9,10 |
|Dermal fillers (poly-L-lactic acid/calcium hydroxylapatite) ||Localized, APL, LD-HIV ||NA ||NA ||Bruising, ...|