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The causes of the inability of insulin infusion systems to restore normal metabolic conditions in diabetic subjects have been investigated with the aid of modeling and computer simulation. It has been possible to compute, by the model, the so-called minimal insulin profile with peripheral insulin infusion, i. e., the time course of plasma insulin which should be observed in a diabetic subject after an oral glucose test, when insulin is infused in a peripheral vein, in order to have a normal blood glucose profile. This profile allows assessment of the performance of insulin infusion systems by evidencing the relative role of the route of infusion and of the control algorithm on the normalization of metabolic control. It is concluded that the route of infusion is of major importance, while the control algorithm plays a minor role. The importance of modeling and simulation in circumstances, which make in vivo experiments; unfeasible or unethical, is emphasized along with the clinical and physiological relevance of the results.