Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility.
Type 1 diabetes mellitus (DM) is a disease of insulin deficiency, resulting from the autoimmune-mediated destruction of pancreatic beta cells. However, as a likely consequence of intraportal insulin deficiency, patients with type 1 DM also exhibit abnormalities of the growth hormone (GH)/IGF/IGF-binding protein (IGFBP) axis, including GH hypersecretion, reduced circulating levels of insulin-like growth factor-I (IGF-I) and IGFBP-3, and elevated levels of IGFBP-1. These abnormalities not only exacerbate hyperglycemia in patients with type 1 DM, but may contribute to the pathogenesis of diabetes-specific complications, including diabetic neuropathy, nephropathy, and retinopathy. Therefore, therapeutic modalities aimed at restoring the GH-IGF-IGFBP axis are being considered. Herein, we review the efficacy of one such therapy, specifically IGF-I replacement therapy. To date, short-term beneficial metabolic effects of recombinant human IGF (rhIGF)-I therapy have been demonstrated in numerous diabetic conditions, including type 1 DM, type 2 DM, and type A insulin resistance. However, the long- term safety and metabolic efficacy of rhIGF-I therapy remains to be established. Moreover, the potential impact of rhIGF-I on the natural history of diabetic complications has yet to be explored.
Thrailkill
K M
KM
Department of Pediatrics, University of Kentucky College of Medicine, Lexington, USA. thrail@pop.uky.edu
D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology; D003929:Diabetic Neuropathies / Q000209:etiology; D003930:Diabetic Retinopathy / Q000209:etiology; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000503:physiopathology
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I