Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance

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The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.