Lipoatrophic diabetes has been 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 months, 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 normoglycaemic 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. There was observed an improvement of ALAT and ASAT, normalization of the fasting
blood glucose, and increased sensitivity to exogenous
insulin. After 11 months of 200 mg
fenfluramine daily addtitional administration of 2 g
clofibrate per day produced normalization of the serum
triglyceride concentration and a marked reduction of the resistance to
insulin. Three more patients with congenital generalized lipodystriphy, two of whom have manifest diabetes, have now started treatment with
fenfluramine and are improving. The rabbits got relapse of their
lipoatrophic diabetes when the
fenfluramine treatment was stopped. It is suggested that a disturbance in the
serotonin metabolism of the central nervous system may be of pathogenetic importance in
congenital generalized lipodystrophy.