Insulin: Potential Negative Consequences of Early Routine Use in Patients With Type 2 Diabetes

The lack of adequate insulin secretion characterizes all hyperglycemic states. When insulin action is normal, as in type 1 diabetes, there is a near total loss of insulin secretory function. In type 2 diabetes, the abnormalities in insulin secretion are multiple. One of the initial defects is a loss of the early phase of meal-stimulated insulin secretion. This is followed by an inability of the β-cell to increase insulin secretion sufficient to overcome hepatic and peripheral insulin resistance. Type 2 diabetes is characterized by a progressive decrease in both β-cell mass and secretory function so that, in most individuals, absolute insulin deficiency occurs in the late stages of the disease. It would seem logical that the ideal treatment for type 2 diabetes should be early and continuing insulin therapy. Unfortunately, there are several characteristics of insulin treatment and insulin action in type 2 diabetes that limit the usefulness of insulin treatment and that suggest that chronic insulin therapy is best used in the later stages of diabetes when there is an absolute deficiency of insulin. In normal physiology, β-cell insulin secretion is coupled immediately with changes in the plasma glucose level (1). The secretory response is rapid (within a minute or two), and because the half-life of insulin is ~5 min, there is little lag time in the glucose regulatory system. Endogenously secreted insulin goes via the portal vein to the liver, where 30–80% of it is either metabolized or used (2). The portal vein-to-peripheral arterial insulin ratio is ~2:1. The administration of insulin exogenously eliminates the rapid regulation of plasma glucose, since the insulin must be taken up slowly and without regulation from the subcutaneous injection site. The kinetics are determined by the nature of the injected insulin formulation. Additionally, as illustrated in Fig. 1, it is necessary …