Therapy of insulin-independent diabetes mellitus: general considerations.

Rational approaches to the therapy of patients with insulin-independent diabetes should be based on correcting the underlying defects. The major metabolic abnormalities present in patients with insulin-independent diabetes are: (1) impaired insulin action, (2) defective glucose-mediated insulin secretion, and (3) hyperglucagonemia. All of these defects could be due to a generalized plasma membrane abnormality that affects insulin and glucose receptors or to a generalized disturbance in postreceptor insulin action. Insulin action may be increased by sulfonylureas, possibly by alterations in intracellular cyclic AMP content, or by weight-reducing diets. Insulin secretion may be increased by gastrointestinal hormones, sulfonylureas, serotonin antagonists, or weight-reducing diets. Individual patients with insulin-independent diabetes have varying degrees of insulin resistance or impaired glucose-mediated insulin secretion. The use of therapeutic agents to correct the predominant defect should provide the most effective means of controlling the hyperglycemia and glucose intolerance of the individual patient.