Pancreatic B-cell function and abnormal urinary peptides in a boy with lipoatrophic diabetes and stenosis of the aqueduct of Sylvius.

A boy with the classical clinical manifestations of acquired lipoatrophic diabetes has been studied for 5 years from the onset of diabetes at age 13. At the age of 15 a ventriculo-cisternal shunt operation was performed because of stenosis of the aqueduct of Sylvius, followed by a dramatic improvement in his diabetic state with a decrease of the 24 hr insulin requirement from 130 to 32 units. After 12 months there was a relapse with increased insulin requirement up to the preoperative level. Pimozide treatment was given for 7 months with no effect on the metabolic derangements. Extremely high basal levels of serum C-peptide and pro-insulin were found throughout the period of observation. A further increase occurred after i.v. arginine infusion tests, indicating hyperfunctioning B-cells. Repeated screenings of peptides in the urine by sephadex chromatography revealed pathological patterns similar to those observed in patients with other hypothalamic disorders, but different from that found in the urine of patients with congenital generalized lipodystrophy. Injection into mice of peptides extracted from the preoperative urine produced an acute hyperglycemia. The mechanisms behind this hypothalamic syndrome are unknown, but it is postulated that the abnormal urinary polypeptides originate from disorganized hypothalamic centres and that these peptides may be responsible for the disturbed carbohydrate and lipid metabolism.