Treatment Of The Hormonal And Metabolic Abnormalities Of Diabetes

Control of hyperglycemia retards progression of microvascular disease in both type 1 and type 2 diabetes. Accordingly, stringent glycemic control is imperative. Yet glycemic control exerts only a modest impact in retarding progression of macrovascular disease. Clearly other steps are needed.

The recently initiated BARI 2D trial has been designed to provide information useful in this regard. Patients are being assigned randomly to stringent and comparable glycemic control with regimens that are either insulin-sensitizing (focusing on glitazones and metformin) or inulin-providing (focusing on insulin and sulfonylureas) regimens. Thus, the potential value of reduction of insulin resistance is being assessed. The effects of the two approaches on activation of coagulation, platelets, and fibrinolysis will be clarified as well.

Because patients with type 2 diabetes are insulin-resistant, provision of exogenous insulin may be the most successful means for providing an adequate supply of substrate for energy in injured cells. By contrast, provision of additional insulin may have potentially deleterious effects such as promoting thrombosis. The provision of insulin may increase the potential for thrombin generation, increased reactivity of platelets, and decrease the fibrinolytic response. In combination, these effects may exacerbate thrombosis, predispose to reocclusion of in-farct-related vessels, and delay resolution of thrombotic occlusion. Accordingly, treatment with insulin in the setting of acute myocardial infarction may entail risk. In addition, induction of hypoglycemic episodes may be particularly deleterious in association with myocardial ischemia. Thus, further study is needed to determine the nature of optimal metabolic control and the method by which it can best be achieved.

Nevertheless, results in the DIGAMI study demonstrated that stringent gly-cemic control at the time of occurrence of acute myocardial infarction reduces the incidence of subsequent cardiac events. The improved outcome is consistent with previously demonstrated beneficial effects of infusion of glucose, insulin, and potassium in nondiabetic subjects who sustain an acute myocardial infarction.

II. ATHEROGENESIS IN DIABETES -

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