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Insulin-independent Diabetes Mellitus: Metabolic Characteristics.

G. Reaven
Published 1980 · Medicine

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Abstract Glucose intolerance in patients with insulin-independent diabetes mellitus can theoretically arise from a loss of normal tissue sensitivity to insulin (insulin resistance) and/or from a decrease in insulin secretory capacity. A review of available literature indicates that both of these defects can exist in these patients. Thus, patients with insulin-independent diabetes mellitus demonstrate a decrease in tissue sensitivity to insulin, and there is a significant relationship between the severity of the glucose intolerance and the magnitude of the insulin resistance in these patients. The relationship between glucose intolerance and insulin secretion in patients with insulin-independent diabetes is more complicated. Patients with mild glucose intolerance tend to have an insulin response to glucose equal to or greater than normal. As the severity of glucose intolerance increases, the insulin response becomes attenuated and patients with severe fasting hyperglycemia become hypoinsulinemic. On the basis of these changes in insulin resistance and insulin secretion, two formulations concerning the pathogenesis of insulin-independent diabetes seem possible. The first is based upon the premise that the basic defect in patients with insulin-independent diabetes is loss of normal tissue sensitivity to insulin. In an effort to maintain glucose homeostasis, increased amounts of insulin are secreted. However, as the need to augment insulin secretion continues, the beta cell may lose the ability to compensate, and frank hypoinsulinemia can supervene. Alternatively, patients with insulin-independent diabetes can be viewed as representing a metabolically heterogeneous group composed of individuals with various degrees of increased insulin resistance and decreased insulin secretory capacity. In this situation, the degree of glucose intolerance will vary as a function of the relative severity of the two metabolic defects. These relatively simple formulations are confounded by the fact that insulin deficiency can lead to insulin resistance, and vice versa, and that obesity will greatly affect insulin resistance and insulin secretion. Thus, the degree of glucose intolerance in any individual is the result of a complex series of relationships between both intrinsic and environmental factors controlling insulin resistance and insulin secretion. Our ability to understand the pathogenesis of insulin-independent diabetes mellitus will depend upon better understanding of these various relationships.
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