Incidence of insulin dependent diabetes in England: a study in the Oxford region, 1985-6.

OBJECTIVE--To determine the incidence of insulin dependent diabetes mellitus up to the age of 21 in a geographically defined population in England with independent validation of completeness of case ascertainment. DESIGN--Prospective registration of newly diagnosed cases supplemented by centralised hospital discharge records and death certificates. Validation of ascertainment from general practitioners. SETTING--Oxford Regional Health Authority area (population 2.4 million). PATIENTS--All patients with insulin dependent diabetes diagnosed below age 21 during 1985-6 and resident in the region at the time of diagnosis. INTERVENTIONS--None. END POINT--Validation of a method of case ascertainment for assessing temporal variation in incidence of insulin dependent diabetes. MEASUREMENTS AND MAIN RESULTS--The overall yearly incidence of newly diagnosed insulin dependent diabetes mellitus in people under 21 was 15.6 cases/100,000 (95% confidence interval 13.6 to 17.6). Among males the incidence was 16.8 cases (14.0 to 19.7)/100,000 and among females 14.3 cases (11.6 to 17.1)/100,000. The highest incidence, in the 10-14 year age group, was 26.4 (20.9 to 31.8) new cases/100,000 population yearly. Case ascertainment was greater than 95%. CONCLUSIONS--The incidence of insulin dependent diabetes in England is considerably higher than reported from large scale studies. It is consistent with described patterns of geographical variation. The figures provide a baseline for assessing temporal change.     

Glutathione Turnover in Cultured Astrocytes: Studies with [15N]Glutamate

The incorporation of [15N]glutamic acid into glutathione was studied in primary cultures of astrocytes. Turnover of the intracellular glutathione pool was rapid, attaining a steady state value of 30.0 atom% excess in 180 min. The intracellular glutathione concentration was high (20-40 nmol/mg protein) and the tripeptide was released rapidly into the incubation medium. Although labeling of glutathione (atom% excess) with [15N]glutamate occurred rapidly, little accumulation of 15N in glutathione was noted during the incubation compared with 15N in aspartate, glutamine, and alanine. Glutathione turnover was stimulated by incubating the astrocytes with diethylmaleate, an electrophile that caused a partial depletion of the glutathione pool(s). Diethylmaleate treatment also was associated with significant reductions of intraastrocytic glutamate, glycine, and cysteine, i.e., the constituents of glutathione. Glutathione synthesis could be stimulated by supplementing the steady-state incubation medium with 0.05 mM L-cysteine, such treatment again partially depleting intraastrocytic glutamate and causing significant reductions of 15N labeling of both alanine and glutamine, suggesting that glutamate had been diverted from the synthesis of these amino acids and toward the formation of glutathione. The current study underscores both the intensity of glutathione turnover in astrocytes and the relationship of this turnover to the metabolism of glutamate and other amino acids.     

Evidence of a Monoaminergic-Cholinergic Imbalance Related to Visual Hallucinations in Lewy Body Dementia

Senile dementia of Lewy body type is characterized clinically by a relatively acute onset of fluctuating memory loss and confusion, frequently accompanied by visual hallucinations. Neurochemical analyses of temporal cortex has revealed a distinction between hallucinating and nonhallucinating patients in both cholinergic and monaminergic transmitter activities. In contrast with the cholinergic enzyme choline acetyltransferase, which was more extensively reduced in hallucinating individuals, serotonergic S2 receptor binding and both dopamine and serotonin metabolites were significantly decreased in nonhallucinating cases. These results suggest that an imbalance between monaminergic and cholinergic transmitters is involved in hallucinogenesis in the human brain.