Chronic Effects and Prevention of Diabetes

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Chapter: Biochemistry : Diabetes Mellitus

As noted previously, available therapies moderate the hyperglycemia of diabetes but fail to completely normalize metabolism.


As noted previously, available therapies moderate the hyperglycemia of diabetes but fail to completely normalize metabolism. The long-standing elevation of blood glucose is associated with the chronic complications of diabetes including premature atherosclerosis as well as cardiovascular disease and stroke, retinopathy, nephropathy, and neuropathy. Intensive treatment with insulin delays the onset and slows the progression of these long-term complications. For example, the incidence of retinopathy decreases as control of blood glucose improves and HbA1c levels decrease (Figure 25.12). The benefits of tight control of blood glucose outweigh the increased risk of severe hypoglycemia in most patients. How hyperglycemia causes the chronic complications of diabetes is unclear. In cells in which entry of glucose is not dependent on insulin, elevated blood glucose leads to increased intracellular glucose and its metabolites. For example, increased intracellular sorbitol contributes to the formation of cataracts in diabetics. Additionally, hyperglycemia promotes the nonenzymic condensation of glucose with cellular proteins in a reaction analogous to the formation of HbA1c. These glycated proteins undergo additional reactions and become advanced glycation end products (AGEs) that mediate some of the early microvascular changes of diabetes and can reduce wound healing. AGEs bind to their receptors (RAGEs), causing the release of proinflammatory molecules. There is currently no preventative treatment for T1D. The risk for T2D can be significantly decreased by a combined regimen of medical nutrition therapy, weight loss, exercise, and aggressive control of hypertension and dyslipidemias. For example, Figure 25.12 shows the incidence of disease in normal and overweight individuals with varying degrees of exercise. The beneficial effect of intensive therapy on cardiovascular disease has not been shown in individuals with long-standing T2D. In contrast, initial intensive control in individuals with newly diagnosed diabetes has long-term benefit in decreasing the risk of myocardial infarction, diabetes-related death, and overall death. The clinical evidence, thus, supports initiating intensive therapy with the goal of lowering HbA1c levels to below 7% as early as possible in the course of diabetes.

Figure 25.12 Relationship of glycemic control and diabetic retinopathy. Hb = hemoglobin.

Figure 25.13 Effect of body weight and exercise on the development of type 2 diabetes.

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