Medical Care
In general, treatment for acquired partial lipodystrophy (APL) is limited to cosmetic, dietary, or medical options.
Currently, no effective treatment exists to halt the progression of lipodystrophy.
Thiazolidinediones have been used in the management of various types of lipodystrophies. They bind to peroxisome proliferator-activator receptor gamma (PPAR-gamma), which stimulates the transcription of genes responsible for growth and differentiation of adipocytes. [32] Several case reports have suggested a beneficial effect from treatment with rosiglitazone or pioglitazone on fat distribution in APL [33, 34] ; however, preferential fat gain was in the lower body.
Following the online publication of a meta-analysis, [35] the Food and Drug Administration issued an alert on May 21, 2007, to patients and health care professionals warning that rosiglitazone could potentially cause an increased risk of myocardial infarction (MI) and heart-related deaths. A thiazolidinedione derivative, rosiglitazone is an antidiabetic agent that improves glycemic control by improving insulin sensitivity. The drug is highly selective and is a potent agonist for PPAR-gamma. Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby reducing blood glucose concentrations and hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema. A large-scale phase III trial (RECORD) has been underway to study the cardiovascular outcomes of rosiglitazone.
As of September 2010, the FDA is requiring a restricted access program to be developed for rosiglitazone under a risk evaluation and mitigation strategy (REMS). Patients currently taking rosiglitazone and benefiting from the drug will be able to continue if they choose to do so. Rosiglitazone will only be available to new patients if they are unable to achieve glucose control on other medications and are unable to take pioglitazone, the only other thiazolidinedione.
For more information, see the FDA’s Safety Alert on Avandia. Additionally, responses to the controversy, including the following articles, can be viewed at Heartwire news (the heart.org, from WebMD): 1) Rosiglitazone increases MI and CV death in meta-analysis, 2) The rosiglitazone aftermath: Legitimate concerns or hype?, and 3) RECORD interim analysis of rosiglitazone safety: No clear-cut answers.
Direct drug therapy is administered according to the associated condition. Membranoproliferative glomerulonephritis (MPGN) and the presence of renal dysfunction largely determine the prognosis of APL. Standard guidelines for the management of renal disease should be followed. The course of MPGN in APL has not been significantly altered by treatment with corticosteroids or cytotoxic medications. Recurrent bacterial infections, if severe, might be managed with prophylactic antibiotics.
Metreleptin, a recombinant analogue of human leptin, has recently been approved to treat the metabolic derangements of lipodystrophy. Leptin is an adipocyte-derived hormone, which is decreased in lipodystrophy, leading to insulin resistance, dyslipidemia, and other metabolic problems. Metreleptin replaces this deficiency, thus improving insulin resistance, hyperglycemia, dyslipidemia, and hepatic steatosis. APL has relatively higher leptin levels and less metabolic derangements. Therefore, the indications for metreleptin are less than for other forms of lipodystrophy. [36, 37, 38, 39]
Surgical Care
The main goal of cosmetic surgical procedures in the treatment of acquired partial lipodystrophy is to minimize the psychological distress and improve quality of life. Several facial reconstruction techniques have been used, with variable success, to restore facial contour. However, surgical intervention cannot restore adipose tissue distribution in other affected areas. Procedures may include the transposition of facial muscles, adipose tissue transplantation (liposuction), and the insertion of silicone or other implants.
The literature is controversial regarding these procedures. The best approach is to individualize the treatment options based on the patient's condition and requirements. These procedures are not recommended for prepubertal children.
Consultations
Early consultation with a nephrologist or an endocrinologist is very important if renal or metabolic complications are suggested. A dietician should be consulted for specialized dietary needs, especially in infants and young children.
Diet
A diet consisting of 50–60% carbohydrate, 20–30% fat, and approximately 20% protein is recommended with restriction of simple sugars. High-fiber complex carbohydrates should be distributed evenly among meals and snacks and consumed with protein or fat. Dietary fat should be primarily cis-monounsaturated fats and long-chain omega-3 fatty acids. [22]
Activity
Regular exercise should be encouraged to help improve metabolic status.
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Fat distribution in acquired partial lipodystrophy.
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Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3NeF, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B to its active enzymatic form. Factor D is expressed to a higher extent in the fat cells of the upper half of the body compared with the lower half, and it is possibly this regional difference that accounts for the restriction of fat loss to the head, arms, and trunk. C3NeF is also associated with type II, dense-deposit membranoproliferative glomerulonephritis in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway.
