Lipodystrophy: metabolic impact and therapeutic challenges

Abstract

The loss of body fat leads to the development of severe metabolic alterations that trigger diabetes, hypertriglyceridemia with consequent pancreatitis, progressive and severe liver disease, and early cardiovascular disease—comorbidities that drastically alter the life expectancy of those who suffer from it.

The deficiency of adipose tissue implies a decrease in leptin, an adipocytokine necessary for the metabolism of carbohydrates, lipids, and fat oxidation. In patients with lipodystrophy, the lack of these mechanisms means that fatty acids that cannot be oxidized accumulate in ectopic organs, generating the multiple pathologies mentioned above.

It is important to highlight the diagnostic difficulties presented by familial partial lipodystrophies, which are the most frequent within the framework of rare diseases. The objective is to deepen the understanding of this rare pathology to avoid late diagnosis and complications. Today we have multiple treatment options, including GLP-1 receptor agonists, dual agonists, and SGLT2 inhibitors, in addition to the specific leptin therapy we know reverses or stabilizes the aforementioned pathologies, achieving good metabolic control. There is ample data in the international literature from patients with lipodystrophy, both partial and generalized, undergoing treatment that has demonstrated the efficacy and safety of leptin replacement therapy. Therefore, all patients with this pathology and with clinical situations that warrant it should receive this treatment.