David Alan Clark

Chapter 22. New Approaches to Diabetes

Publisher Summary Several new mechanisms for the therapy of diabetes show considerable promise for the expansion of the clinical options for the treatment of hyperglycemia. As new pharmacological classes of anti-diabetic agents emerge, optimal treatment of non-insulin dependent diabetes mellitus (NIDDM) may require combination therapies. These may be adjusted to suit individual patient needs, particularly if responsiveness to therapies is as heterogeneous as it can be expected in so large a clinical population. Insulin replacement therapy of insulin dependent diabetes mellitus (IDDM) may be optimized by the development of more physiological insulin replacements and correction of other secondary hormonal changes. This chapter discusses several promising new approaches that may represent the potential therapeutic breakthroughs in the treatment of hyperglycemia in diabetes mellitus with emphasis on insulin, insulin release, insulin action, and counter-regulatory hormones. Therapy of IDDM or Type I diabetes attempts to replace insulin in a manner that mimics the physiologic pattern of release seen in the nondiabetic. In addition, insulin is used in the treatment of NIDDM or Type II diabetes when oral therapy alone fails. NIDDM is characterized by abnormal insulin secretion from the pancreas, increased basal glucose output by the liver, and insulin resistance in peripheral tissue. Peripheral insulin resistance significantly contributes to the hyperglycemic state of NIDDM, as proven by euglycemic insulin clamp studies that show a marked reduction in insulin stimulation of glucose disposal. Current data favor a post-receptor defect in response to insulin. A reduction of glycemia also alleviates the resistance to insulin action in peripheral tissues. These act to counter insulins action in stimulating peripheral glucose disposal and inhibiting hepatic glucose output. Modulation of these counter regulatory hormones can impact the glycemic control and/or insulin action in diabetic patients.