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Recent Advances Relative To Diabetes Mellitus



Recent Advances Relative To Diabetes Mellitus



Annals of Internal Medicine 63: 512-529



Most cases of diabetes are due to a genetic disorder, the primary defect of which is unknown. Apparently it is riot due to a deficiency of insulin secretion. One possibility that has received extensive interest recently is an abnormality in the metabolism of insulin, possible produced by the liver. Under certain circumstances, an excessive amount of insulin-like material of high molecular weight, is demonstrable in the plasma of diabetics. The exact composition of this material has not been established. It possibly consists of polymers of either many insulin molecules or of various other combinations of chain A and B of insulin. It has been shown that one species of A chain can be re-conjugated with the B chain of another species and vice versa, producing insulin activity. Whereas this material is capable of stimulating activity of the adipose tissue, much of it is incapable of stimulating muscle tissue. The excessive activity on adipose tissue has been postulated as being the basis for the commonly observed obesity in adult diabetics. Diabetic serum has been reported to contain more of the synalbumin factor, less augmentation of insulin action by plasma globulin fractions as well as far greater complexing of insulin. Certain investigators have recently proposed that a defect in lipid metabolism may be a major producer of "alterations in carbohydrate metabolism in diabetes. According to this thesis, there is increased lipolysis in diabetics with the liberation of excessive quantities of free fatty acids, leading to refractoriness of insulin activity in promoting glucose uptake by the cells of certain peripheral tissue. Oral therapy has increased considerably in popularity, however, there is much to suggest that sulfonylureas and phenformin should be used simultaneously in many more patients than in the past. With continued sulfonylurea therapy, as with phenformin, plasma insulin levels tend to become lower than the pretreatment levels. Such observations should allay some of the anxiety about sulfonylurea therapy exhausting the beta cells and causing an increase in obesity via hyperinsulinism.

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Accession: 025349041

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PMID: 14327514


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