Nonketotic diabetes mellitus: insulin deficiency or insulin resistance?

Ninety-five nonobese, nonketotic subjects were divided into five groups (one normal and four with varying degrees of glucose intolerance) according to their plasma glucose responses during an oral glucose tolerance test. These five groups were then compared on the basis of their insulin response during the oral glucose tolerance test and on the ability of exogenously infused insulin to limit hyperglycemia during a continuous infusion of glucose and insulin, while endogenous insulin was inhibited by the infusion of epinephrine and propranolol. The mean plasma insulin response of patients with either borderline abnormalities of glucose tolerance or chemical diabetes was equal to or greater than that of normal subjects at all points during the glucose tolerance test. Thus, the glucose tolerance of these two patient groups cannot be attributed to lack of insulin. On the other hand, the mean insulin response of patients with moderate fasting hyperglycemia (plasma glucose of 110 to 150 mg/100 ml) was somewhat attenuated, and patients with severe fasting hyperglycemia (plasma glucose greater than 150 mg/100 ml) had unequivocal insulin deficiency. In contrast, all four patient groups with abnormal carbohydrate metabolism were more resistant than normal subjects to the action of insulin. These results indicate that there is a very complex relationship between insulin deficiency and insulin resistance in patients currently classified as having nonketotic diabetes. Patients with either borderline abnormal glucose tolerance or chemical diabetes are more resistant to insulin than normal subjects, and are not insulin deficient. In these patients it seems reasonable to assume that their glucose intolerance is a direct function of their insulin resistance. Patients with severe fasting hyperglycemia are suffering from both insulin deficiency and insulin resistance, and the relationship between these two variables in the genesis of hyperglycemia in these subjects remains obscure. It seems apparent from these studies that nonketotic diabetes mellitus can no longer be considered to be a simple function of insulin lack, and that in order to understand this syndrome we will need to increase our knowledge of the relationship between insulin deficiency and insulin resistance in these patients.