An impaired insulin response to glucose is a characteristic finding in maturity onset diabetes (MOD). To clarify whether the decreased insulin response in vivo is related to a primary defect of the beta-cells, isolated islets of MOD - obtained by intraoperative biopsy - were examined for their insulin content, biosynthesis and release. The in vitro experiments showed that despite a missing or significantly reduced insulin response in vivo the isolated beta-cells of the same patients had a normal insulin content, a normal or even high biosynthesis, and insulin release could be induced by glucose. These results suggest that the primary defect in MoD cannot be related to an intrinsic failure of the beta-cells to response to glucose; extrapancreatic factors seem to influence their reaction to glucose. These factors may be of a higher level in those patients or the reaction of the beta-cells is more inhibited by the same concentrations in diabetic patients.

The lacking or reduced insulin response to glucose infusion is typical of diabetes mellitus. Nevertheless it is possible to verify a significant increase of the serum insulin level in maturity onset diabetics following tolbutamide of glucagon injection when reaction to oral glucose administration is missing. We examined whether it is possible to ob ta in a stimulation of insulin secretion by maximum increase of the blood glucose level by intravenous administration of glucose. For this purpose 9 diabetic patients have been studied. The patients received 0.75 g glucose per kg of body weight initial-Iy and therafter an infusion of 30 mg glucose per kg of body weight per minute during 30 minutes. Despite the blood glucose increase up to 1000mg/100 ml under intravenous infusion no stimulation of insulin secretion by the glucose took place. The same patients showed a significant insulin increase after stimulation with tolbutamide or glucagon. However, this response has been observed in patients also in cases where the oral stimulation with 100 g glucose did not result in any secretion whatever. This type of insulin secretion probably results from a completc alteration of the glucose receptor in respect of stimulation with glucose. ToLbutamide and glucagon rcceptors seem to be intact.

A highly significantly decreased prevalence of insulin-dependent childhood-onset diabetes (less than 1/3 of the initial prevalence rate) could be achieved in Berlin/GDR since 1973 by improving systematically diagnostic and therapeutic measures for pregnant diabetics, particularly for non-insulin-dependent gestational diabetics. In addition, a highly significantly increased incidence rate of diagnosed, diet-treated and delivered non-insulin-dependent pregnant diabetics was found between 1979 and 1983 in Berlin/GDR, Halle and Leipzig as compared to the other districts of the GDR. Simultaneously, a highly significantly decreased prevalence rate of diabetic children (less than 1/3), who were born during this period, was found in 1983 for Berlin, Halle and Leipzig as compared to the other districts of the GDR. Finally, a highly significant inverse correlation could be demonstrated for the 15 districts of the GDR between the incidence rates of diagnosed, diet-treated and delivered non-insulin-dependent pregnant diabetics and the prevalence rates of diabetic children who were born during this period (1979-1983). In view of these findings, an interruption and even a reversal of the continued dramatic increase of idiopathic insulin-dependent diabetes mellitus appears to be possible in the developed countries by preventing maternal hyperglycaemia during pregnancy and hence hyperinsulinism in the foetuses and newborns.

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Many cases of type II diabetes present an anomaly of insulin secretion which is characterized by a missing, reduced, or delayed glucose-stimulated insulin output from the beta cell. We aimed at finding out whether this characteristic disorder is a consequence of reduced beta cell mass or of a more functional disturbance. In the latter case it was to be clarified whether the disturbed beta cell "glucoreceptor" function represents a qualitative or rather a quantitative difference. By the evaluation of insulin secretion and of carbohydrate tolerance during oral and/or intravenous intake of glucose, and after intravenous application of tolbutamide or glucagon the defective insulin secretion in type II diabetics was found to represent a more functional disturbance which could not be explained by reduction of beta cell mass. Thus it was concluded that the anomaly of insulin secretion mentioned above might be a consequence of a qualitative defect of the glucoreceptor. To prove this, isolated human islets (insulin secretion under incubation with glucose, measurements of 3H-leucine incorporation and of the insulin content) were also studied. In contrast to the in vivo results, insulin release of the isolated islets of type II diabetics was normal. From this it must be concluded that the glucoreceptor of the beta cell, which in vivo reacts in a qualitatively different manner from that of subjects with intact metabolism, is not irreversibly disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)