Circulating IGF-I and its protective role in the pathogenesis of diabetic angiopathy.
Poor glycaemic control in type 1 diabetes is associated with elevated serum IGFBP-1 levels and reduced rather than elevated serum IGF-I levels. Increasing age is accompanied by a further decrease in serum IGF-I levels as well as an increase in IGFBP-l levels in adult diabetic type 1 and type 2 subjects. This is especially observed in diabetic type 1 subjects with manifest microvascular complications. IGFBP-I has been proposed as one of the IGF-I inhibitors in the serum of diabetics. Lowered IGF-I and increased IGFBP-1 levels in the blood may thus result in decreased IGF-I bioavailability at the tissue level. We hypothesize that the premature and progressive decline in serum IGF-I bioactivity during ageing in diabetics ultimately results in insufficient protective effects by IGF-I in the kidneys, eyes and neurones, and thus the progression of diabetic microvascular complications. If this hypothesis is proven to be right, treatment of diabetic patients with IGF-I (eventually complexed to IGFBPs) as an adjunct to insulin might prevent and not worsen the development of diabetic microvascular complications.
Janssen
J A
JA
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
Lamberts
S W
SW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000627:therapeutic use; D008875:Middle Aged
D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone