The real mechanism of hypoglycemia caused by non-islet cell tumors was still unclear in the 1970s and the early 1980s, when circulating insulin-like peptides were described.[8,9] In 1988, Daughaday et al[10] studied abnormal (incompletely processed) IGF-II, and finally described high molecular weight or “large” IGF-II,[11] which has strong insulin-like activity and leads to hypoglycemia. This evidence concerns the gene INS and Hypoglycemia.