Insulin Resistance and Insulin Secretion in Patients with Chemical Diabetes: Implications Concerning the Pathogenesis of Idiopathic Diabetes Mellitus

Abstract

It has been apparent since the introduction of the radioimmunoassay for insulin that patients with idiopathic diabetes mellitus can be hyperglycemic in the face of normal to elevated levels of plasma insulin (1). On the other hand, there are patients with diabetes mellitus who demonstrate absolute insulin deficiency (1). This issue has been considered in detail (2), and certain generalizations have emerged. Significant numbers of diabetic patients with the mildest form of diabetes (chemical diabetes) are hyperglycemic in spite of circulating insulin levels which are equal to or greater than those seen in normal subjects. As the magnitude of hyperglycemia increases, the insulin response begins to fall off. Lowest plasma insulin concentrations are seen in patients with the most severe degrees of hyperglycemia, and there is agreement that ketosis-prone diabetics are hyperglycemic as the result of absolute insulin deficiency. This relationship between plasma glucose and insulin responses to an oral glucose challenge was explicitly described more than 10 years ago in a Caucasian population (3), and more recently been observed in Pima Indians in the United States (4), and in a Micronesian population in the Central Pacific (5).