Chronic Effects and Prevention

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 vascular complications of diabetes including cardiovascular disease (CVD) and stroke (macrovascular complications) as well as retinopathy, nephropathy, and neuropathy (microvascular). Intensive insulin treatment  delays the onset and slows the progression of some long-term complications. For example, the incidence of retinopathy decreases as control of blood glucose improves and HbA1c levels decrease (Fig. 1). [Note: Data concerning the effect of tight control on CVD in T2D are less clear.] 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 glucose uptake is not dependent on insulin, elevated blood glucose leads to increased intracellular glucose and its metabolites. For example, increased intracellular sorbitol contributes to cataract formation  in diabetes. Additionally, hyperglycemia promotes glycation of cellular proteins in a reaction analogous to the formation of HbA1c. These glycated proteins undergo additional reactions and become advanced glycation end products (AGE) that mediate some of the early microvascular changes of diabetes and can reduce wound healing. Some AGE bind to a membrane receptor (RAGE), 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 2 shows the incidence of disease in normal and overweight individuals with varying degrees of exercise.

Figure 1: Relationship of glycemic control and diabetic retinopathy. HbA1c = glycated hemoglobin.

Figure 2:  Effect of body mass index and exercise on the development of type 2 diabetes.