**5. Management**

Patients with lipodystrophy normally seek medical treatments toward the specific symptoms that they encounter. Since the disease affects its patients in multiple

#### *Lipodystrophy - A Rare Condition with Serious Metabolic Abnormalities DOI: http://dx.doi.org/10.5772/intechopen.88667*

aspects, care and management require a multidisciplinary team involving pediatricians, surgeons, cardiologists, endocrinologists, nutritionists, and psychiatrists [20]. Mental health supports should also be made to patients who suffer depressions from the diagnosis and anxieties about their appearance [142]. In addition, special education might be necessary for those who have an intellectual disability [142]. Furthermore, such cosmetic surgery as reconstructive facial surgery and bilateral gluteus maximus muscle flap advance might benefit the patients in improving their appearance and quality of life [20].

Dietary restriction is of paramount importance in the disease management. Particularly, those with CGL should follow a high-carb and low-fat diet, since it can raise very-low-density lipoprotein (VLDL) TAG levels while alleviating chylomicronemia [143]. Sufficient energy supply along with regular exercise is highly important in children with CGL to ensure their normal growth [20]. However, strenuous exercise is not recommended for CGL4 patients who can be treated with β-adrenergic blockers along with other antiarrhythmic medications to prevent catecholaminergic polymorphic ventricular tachycardia [144]. Also, in this case, an implantable pacemaker or defibrillator can be quite beneficial [144]. It remains unclear whether patients with CGL2 and cardiomyopathy should restrict exercise [145].

The first-line therapy for diabetes mellitus, such as metformin and sulphonylureas, can be prescribed to patients with CGL [146]. The lack of subcutaneous fat in the abdomen and thighs might pose a potential barrier for insulin injection, and the patients might necessitate higher doses of insulin [147]. Furthermore, kidney damage such as diabetic nephropathy and end-stage renal disease might occur in patients with long-standing diabetes as the result high blood glucose exposure. Treatments for such condition might involve hemodialysis and kidney transplantation [20].

Metreleptin can be a promising therapeutic drug in the near future as recent studies have shown its potency in improving metabolic complications involving diabetes mellitus, hypertriglyceridemia, and hepatic steatosis in CGL [146, 148–151]. In fact, 63% reduction in circulating levels of TAG along with 30% increase in insulin sensitivity, and 20% reduction in liver volume are observed in seven patients treated with metreleptin over the period of 4 months [20]. Three patients with CGL2 and two patients with CGL treated with recombinant leptin therapy in Japan during the treatment course of 36 months have shown ameliorated fasting glucose and TAG levels as well as increased insulin sensitivity [152]. Metreleptin therapy can also reduce symptoms of other conditions such as macroalbuminuria, microalbuminuria, and hyperfiltration as well as improve the balance in sex hormone profile [151, 152]. Patients treated with metreleptin might suffer such adverse effects as hypoglycemia, headache, nausea, decreased weight, and abdominal pain [153, 154]. In addition, there is a rare possibility that antileptin antibodies might develop severe infections [154]. Metreleptin therapy can reduce appetite signaled from the hypothalamus, as *Agpat2*<sup>−</sup>/<sup>−</sup> mice with selective deletion of leptin receptor do not respond to the treatment [153]. The use of metreleptin in combination with dietary management has been approved by the Food and Drug Administration in the treatment for patients with CGL and APL in 2014, and Japan has approved it to be an anti-lipodystrophic drug in 2013 [20].

## **6. Conclusions**

Lipodystrophy is a rare genetic disease characterized by near-total loss or partial loss of body fat. The syndrome can result in an array of metabolic complications such as insulin resistance, type 2 diabetes, hypertriglyceridemia, and hepatic steatosis. The disease is managed with dietary restriction and exercise programs in line with the leptin therapy.

*Rare Diseases*
