CONGENITAL GENERALIZED LIPODYSTROPHY AND EXPERIMENTAL LIPOATROPHIC DIABETES IN RABBITS TREATED SUCCESSFULLY WITH FENFLURAMINE

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Abstract
Lipoatrophic diabetes was produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 mo., respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy. The rabbits became normoglycemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed. His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off and the pigmentations of the skin decreased. An improvement of ALAT [alanine aminotransferase] and ASAT [aspartate aminotransferase] normalization of the fasting blood glucose and increased sensitivity to exogenous insulin was observed. After 11 mo. of 200 mg fenfluramine daily, additional administration of 2 g clofibrate/day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystrophy, 2 of whom have manifest diabetes, have now started treatment with fenfluramine and are improving. The rabbits had a relapse of their lipoatrophic diabetes when the fenfluramine treatment was stopped. A disturbance in the serotonin metabolism of the CNS may be of pathogenetic importance in congenital generalized lipodystrophy.

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