In this article we describe the evolution of the modifications we made in our clinic to glucose challenge protocols or mathematical models of insulin secretion, insulin sensitivity and glucose effectiveness, in order to study these parameters in patients with Insulin-Requiring Type2 Diabetes (T2D) and Type 1 diabetes (T1D), including T1D patients who have received Islet Transplants to treat their severe recurrent hypoglycemia and impaired awareness of hypoglycemia. Here, INS is linked to Hypoglycemia.