Role of insulin receptors in obesity-related diabetes.

Insulin binding to monocytes was assessed before and after plasma insulin suppression by diazoxide in 14 obesity-related diabetic subjects. Four of the five patients with mild carbohydrate intolerance (FBS less than 150 mg%) and hyperinsulinism exhibited low monocyte insulin binding. Despite an increase in insulin binding after 7 days of diazoxide therapy, no improvement in carbohydrate tolerance could be demonstrated. Lack of improvement may have been related to persistent diazoxide effect. An additional group of 4 patients with low plasma insulin values and more severe carbohydrate intolerance (FBS greater than 150 mg%) had high monocyte insulin binding. This group, as well as a group of patients with intermediate insulin responses, tolerated diazoxide poorly and developed moderate ketonuria or severe hyperglycemia (plasma glucose greater than 350 mg%) necessitating discontinuation of the drug after 3-6 days. The studies in these patients suggest that obesity-related diabetes may be characterized early by mild elevation of plasma glucose, hyperinsulinism and impaired monocyte insulin binding. As beta cell exhaustion occurs, more severe hyperglycemia intervenes and insulin binding to monocytes increases.