Die orale Diabetesbehandlung mit Sidfonylharnstoffen unter dem Aspekt des endokrinen Defekts beim Altersdiabetes (Part 1 of 2)

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Abstract
The indications for oral diabetic treatment by sulfonylureas (SU) is limited to adult diabetics. There are 2 reasons for this restrictive application: the mechanism of action of these drugs and the peculiar nature of the insulin deficit in adult diabetes. The SU do not influence the carbohydrate metabolism of the peripheral tissue (fat and muscles) depending on the insulin system. Their hypoglycemic action is due to a direct effect upon the endocrine regulation of the carbohydrate metabolism. Experiments with animals have shown how the insulin producing B cell system of Langerhan''s islets is stimulated by SU to mobilize its deposits of insulin. If the insulin producing cell system is lacking (after pancreatectomy or after complete destruction by alloxan) hypoglycemia does not follow administration of these compounds. Adult diabetics, in contrast to the so-called juvenile diabetics who lack endogenous insulin, can mobilize endogenous insulin and so benefit from oral treatment with sulfa drugs. A cure of the disease is not obtained. This fact can be explained by thoroughly analyzing the endocrine defect and measuring the serum insulin inactivities: the physiological stimulation of hyperglycemia in adult diabetes cannot liberate at all, or can only insufficiently liberate, biologically active insulin. Although by SU this rigid system of insulin secretion is split, the regeneration of insulin to be mobilized after the liberation is delayed due to SU. Human growth hormone, too, leads to short block of insulin production. The endocrine defect of adult diabetes may be considered as an incomplete B cell insufficiency with a functional lack of insulin as regards the needs of carbohydrate metabolism, in other terms, a disturbance of insulin secretion. Only this part of the defect is influenced for a short time by sulfa drugs. A remarkable improvement of the endogenous insulin metabolism in adult diabetes results. The disturbance of the insulin production remains. It is not known yet whether treatment by SU in the stage of prediabetes or a combination of SU with exogenous insulin therapy in beginning adult diabetes may bring about a remission or inhibit the diabetes from becoming manifest. For the time being we have to be satisfied with the possibility of determining by means of SU the types and degrees of insulin insufficiency and insulin deficiency in the different forms of diabetes and to work out from the knowledge obtained an efficient antidiabetic therapy (diet, drugs) according to pathogenetic principles. Antidiabetic treatment has, therefore, gained a sound theoretical basis.

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