W(h)ither Metreleptin for Lipodystrophy and the Metabolic Syndrome?

Abstract

Lipodystrophy, congenital or acquired, partial or generalized, is a disorder characterized by pathologic deposition of adipose tissue (lipoatrophy, lipohypertrophy, or both) accompanied by metabolic abnormalities ( 1 Gao C Mantzoros CS Lipodystrophy syndromes. in: Jameson JL De Groot LJ Endocrinology.6th ed. Elsevier, Mosby, Saunders, Philadelphia, PA2010 Crossref Google Scholar ). Lipodystrophy is extremely rare among human immunodeficiency virus (HIV)-negative subjects; it is estimated that worldwide there are only several hundred subjects with either congenital lipodystrophy or non-HIV-associated acquired lipodystrophy ( 1 Gao C Mantzoros CS Lipodystrophy syndromes. in: Jameson JL De Groot LJ Endocrinology.6th ed. Elsevier, Mosby, Saunders, Philadelphia, PA2010 Crossref Google Scholar , 2 Grinspoon S Carr A Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005; 352: 48-62 Crossref PubMed Scopus (878) Google Scholar , 3 Leow MK Addy CL Mantzoros CS Clinical review 159: human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome; clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003; 88: 1961-1976 Crossref PubMed Scopus (104) Google Scholar ). The widespread use of combinations of antiretroviral agents for the treatment of HIVpositive patients since the 1990s, however, has resulted in the development of a new syndrome, the HIV/hightly active antiretroviral therapy (HAART)-associated lipodystrophy and metabolic syndrome (HALS) ( 3 Leow MK Addy CL Mantzoros CS Clinical review 159: human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome; clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003; 88: 1961-1976 Crossref PubMed Scopus (104) Google Scholar ). In contrast to the extremely low prevalence of non-HIV-associated lipodystrophy worldwide, there are several hundreds of thousands of HIV-positive patients who have HALS, with approximately 200,000 of them having lipoatrophy (adipose tissue deficiency) and hypoleptinemia ( 1 Gao C Mantzoros CS Lipodystrophy syndromes. in: Jameson JL De Groot LJ Endocrinology.6th ed. Elsevier, Mosby, Saunders, Philadelphia, PA2010 Crossref Google Scholar , 2 Grinspoon S Carr A Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005; 352: 48-62 Crossref PubMed Scopus (878) Google Scholar , 3 Leow MK Addy CL Mantzoros CS Clinical review 159: human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome; clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003; 88: 1961-1976 Crossref PubMed Scopus (104) Google Scholar ).