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Congenital generalized lipodystrophy and experimental lipoatrophic diabetes in rabbits treated successfully with fenfluramine.

Abstract
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.
AuthorsO Trygstad, I Foss
JournalActa endocrinologica (Acta Endocrinol (Copenh)) Vol. 85 Issue 2 Pg. 436-48 (Jun 1977) ISSN: 0001-5598 [Print] Denmark
PMID577333 (Publication Type: Journal Article)
Chemical References
  • Blood Glucose
  • Indoleacetic Acids
  • Triglycerides
  • Pimozide
  • Fenfluramine
  • Serotonin
  • Prednisolone
Topics
  • Adult
  • Animals
  • Blood Glucose (analysis)
  • Brain (metabolism)
  • Diabetes Complications
  • Diabetes Mellitus (chemically induced, drug therapy)
  • Fenfluramine (therapeutic use)
  • Glucose Tolerance Test
  • Humans
  • Indoleacetic Acids (urine)
  • Lipodystrophy (complications, congenital, drug therapy)
  • Pimozide (therapeutic use)
  • Prednisolone
  • Rabbits
  • Serotonin (metabolism)
  • Triglycerides (blood)

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