BACKGROUND: Ideally, optimal treatment of T1DM should achieve near-normal glucose with no hypoglycemias and preserved quality of life. In the clinical arena, even the currently available most complex strategy, i.e. glucose sensor augmented insulin pump therapy, in which patients wear both a pump for subcutaneous insulin delivery (CSII) and a subcutaneous glucose sensor for continuous glucose monitoring (CGM), does not fully meet the patients' needs. Artificial pancreas (AP) or integrated closed loop control (CLC) algorithms -which take into account CGM readings and the effects of previous insulin infusions to continuously compute the amount of insulin dose to be administered- aim to minimize, in real time, glucose variability and prevent extreme glucose excursions. A number of research groups have been brilliantly working for years to develop a wearable AP to partially, or totally, free the patient (and/or the caregiver) from the burden of the open loop control. However, a perfect glucose control is still lacking, especially in post-meal glycemic excursions. Further insights might be gained by studies of the substrate/hormone responses to meals in T1DM patients on sensor augmented CSII, possibly compared with the gold standard of normal physiology, with special regard to the relative role played by a number of factors of the glucose-insulin pump system in controlling glucose levels.