RSS Feeds
Lipoatrophy, Lipodystrophy, and Insulin Resistance
In 1946, R.D. Lawrence described the characteristics of lipoatrophic diabetes, an unusual constellation of generalized absence of adipose tissue, insulin-resistant diabetes mellitus, absence of ketosis, marked lipemia with hepatomegaly, and elevated basal metabolic rate (1). More than 100 cases with similar features have been reported in the literature thus far (2, 3). Although the syndrome is rare, its true prevalence in unknown because of the heterogeneity of clinical features in individual patients.
The absence of adipose tissue, initially considered to be a sine qua non, does not affect all parts of the body in many patients (hence the term lipodystrophy), and although insulin resistance is demonstrable in all patients, overt diabetes may not always be present. However, patients with overt diabetes may require hundreds of units of insulin daily. The syndrome may be congenital or acquired, sporadic or familial. Other clinical features of the syndrome, more frequently seen in congenital or familial cases, include acanthosis nigricans, hirsutism and virilism, accelerated growth, acromegaloid features, hypertrophy of skeletal and cardiac muscle, and hepatic cirrhosis.
A genetic link has been reported in some families, but the mechanism of insulin resistance and related consequences in patients with marked paucity of adipose tissue remains uncertain. Recently, three groups of investigators reproduced most of the features of congenital generalized lipodystrophy (the Seip–Berardinelli syndrome) in transgenic mice by altering the expression of transcription factors involved in adipocyte differentiation since birth (4-6). In one of these fascinating models (5), transplantation of …
