 Putting these considerations together, we propose a multi-factorial working model which, while emphasizing the central role of the function of the pancreatic beta cells, also will include factors mediating insulin resistance, as well as those controlling the metabolism of the atypicals, and their effects on the central nervous system. Such a model concurrently considers genetic and other factors that might determine the effects of the atypicals and factors altering glucose homeostasis in target tissues, as well as the interactions among these factors. 