Theoretically, both IGF-I and IGF-II are capable of decreasing glucose levels, but, they fail to do so because they are normally trapped within the vascular vessel in a high molecular weight protein complex with IGFBP3 and acid-labile subunit (ALS).12–14 The big IGF-II reside in the binary complex with IGFBP3 which was considered to be capable of crossing the endothelial barrier, resulting in a persistent insulin-like activity and leading to severe hypoglycemia.15,16. Here, IGFBP3 is linked to Hypoglycemia.