Ithink it’s remarkable that only a few months after Banting introduced insulin to the world of diabetes, on the heels of one of medicine’s greatest discoveries, Elliot Joslin wrote,“insulin is not a cure for diabetes, but a potent preparation alike... for evil and for good.” Today, 85 years later, with all the advances in insulin therapy, there is still a dark side to this potent preparation, and it is hypoglycemia. Hypoglycemia is the major barrier preventing insulin from achieving its full, therapeutic promise.

My story begins 30 years ago. Bill Tamborlane came to me with a portable, battery-powered pump being used in pediatrics to infuse the iron-chelating drug desferrioxamine continuously via the subcutaneous route into children with thalassemia major. He hoped to use it to treat children with glycogen storage disease, a study we never performed. This relatively small pump, the Autosyringe Model AS2C, was at that time relatively unique. It had an “instant dose” button that allowed for bolus dose administration as well as the ability to deliver solutions continuously. In short, it was a “perfect” vehicle to infuse insulin in diabetes. Improved glucose control had been demonstrated earlier in the inpatient setting in type 1 diabetic patients given continuous intravenous insulin delivered at preprogrammed basal rates with increments before meals. Such systems were not practical outside of a controlled environment. This device, however, was small enough to be used for continuous subcutaneous insulin delivery. My enthusiasm for this idea was based on experiments Luigi Sacca and I performed 2 years earlier in the mid 1970s. We demonstrated that overnight basal insulin infusion in doses sufficient to normalize fasting glucose the next morning restored the ability of hyperglycemia to suppress hepatic glucose production in type 1 diabetic patients, despite their failure to release insulin (1). Those studies suggested that if insulin were delivered at more physiological basal rates (something that was not easy to achieve with the intermediate-acting insulin available at the time), it would not only provide better regulation of fasting glucose but also minimize postprandial hyperglycemia after a breakfast meal. The second study made me think that open-loop continuous insulin delivery might be relatively safe. In that study, we infused insulin to “conventionally”(which at that time was poorly) treated type 1