The thiazolidinediones agents belong to a unique class of oral antidiabetic agents that exert direct effects on the mechanisms of insulin resistance, which is a major pathophysiologic abnormality in type 2 diabetes. Through effects on PPAR-y, the thiazolidinediones regulate the expression of numerous genes affecting carbohydrate and lipid metabolism and vascular function. These effects result in improved glycemia and lower insulin requirements in type 2 diabetics. Preliminary evidence also suggests that the thiazolidinediones improve other components of the insulin-resistance syndrome and thereby may be able to prevent or delay premature atherosclerotic cardiovascular disease, morbidity, and death. However, in a small minority of patients, weight gain and edema remain undesirable side effects of these agents and the thiazolidinediones should not be used in patients with advanced degrees of CHF. In the future, it is possible to envisage the availability of tailored thiazolidinedione or even non-thiazolidinedione compounds which through their selective agonist effects will have enhanced beneficial effects on glucose, lipid and vascular endothelial metabolism and through their partial agonist, or even selective antagonist effects, do not possess the unwanted side effects of weight gain and fluid retention. The ultimate goal in the treatment of diabetes is the prevention of the disease. Preliminary evidence suggests that the thiazolidinediones have the potential to delay or even prevent the development of type 2 diabetes in high-risk individuals.

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