Glucose control and insulin resistance in non-insulin-dependent diabetes mellitus

Chronic hyperglycemia is implicated in the pathogenesis of microvascular, neurologic, and macrovascular complications of diabetes. Recent studies prove that near-normal glycemic control in insulin-dependent diabetes mellitus (IDDM) reduces the risk for the development and progression of microvascular and neurologic complications. With the expectation of comparable benefits, similar glycemic goals have been advocated for the management of non-insulin-dependent diabetes mellitus (NIDDM). However, using intensified insulin therapy to achieve near-normal glycemia in NIDDM may be problematic because of basic differences in the pathophysiology of the two types of diabetes. Insulin resistance is a major contributor to the development of hyperglycemia in NIDDM and may prevent attainment of normoglycemia in most patients who are using the conventional approaches of diet, exercise, and oral hypoglycemic therapy. Near-normal glycemia in patients with NIDDM can usually be achieved with exogenous insulin but often requires large doses to overcome the insulin resistance. Intensive insulin therapy normalizes glycemia by decreasing hepatic glucose output and improving peripheral glucose uptake and may also improve insulin resistance and insulin secretion by reducing hyperglycemic glucotoxicity. However, large doses of exogenous insulin are associated with hyperinsulinemia and weight gain, but these effects may be minimized by combining insulin with other forms of therapy, for example, oral antidiabetic agents. When intensive management is instituted, the dose of exogenous insulin should be kept as low as possible. To do this, therapy for NIDDM must be part of a multifaceted approach combining insulin therapy with other effective forms of treatment such as counseling on diet and exercise therapy and the use of oral antidiabetic agents.