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Dr Spellman is an associate professor of medicine and the chief of the Division of Endocrinology at the University of North Texas Health Science Center at Fort Worth—Texas College of Osteopathic Medicine.

Address correspondence to Craig W. Spellman, DO, PhD, 855 Montgomery St, Ft Worth, TX 76107-2553. E-mail: cspellma{at}hsc.unt.edu

The epidemic of type 2 diabetes mellitus is increasing in most nations. This illness is a major cause of cardiovascular disease, stroke, blindness, renal failure, and amputations. Because available interventions have failed to show durability, new modes of therapy need to be directed at the underlying causes of abnormal glucose metabolism. The development of such modes of therapy will require an improved understanding of how the ß-cell mass compensates for changes in insulin resistance and why ß cells lose the capacity to secrete insulin. In addition, new therapeutic modalities need to address -cell dysregulation, because the inability to suppress glucagon production results in ongoing elevated levels of hepatic glucose.