The role of IGF-I and its binding proteins in the development of type 2 diabetes and cardiovascular disease.
Patients with insulin resistance and type 2 diabetes have an excessive risk of cardiovascular disease (CVD); this increased risk is not fully explained by traditional risk factors such as hypertension and dyslipidaemias. There is now compelling evidence to suggest that abnormalities of insulin-like growth factor-I (IGF-I) and one of its binding proteins, insulin-like growth factor-binding protein-1 (IGFBP-1), occur in insulin-resistant states and may be significant factors in the pathophysiology of CVD. We reviewed articles and relevant bibliographies following a systematic search of MEDLINE for English language articles between 1966 and the present, using an initial search strategy combining the MeSH terms: IGF, diabetes and CVD. Our aim was first to review the role of IGF-I in vascular homeostasis and to explore the mechanisms by which it may exert its effects. We also present an overview of the physiology of the IGF-binding proteins, and finally, we sought to summarize the evidence to date describing the changes in the insulin/IGF-I/IGFBP-1 axis that occur in type 2 diabetes and CVD; in particular, we have focused on the potential vasculoprotective effects of both IGF-I and IGFBP-1. We conclude that this system represents an interesting and novel therapeutic target in the prevention of CVD in type 2 diabetes.
Ezzat
Vivienne A
VA
Cardiovascular Division, The James Black Centre, Kings College London, Denmark Hill Campus, London, UK.
Duncan
Edward R
ER
Wheatcroft
Stephen B
SB
Kearney
Mark T
MT
D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D003925:Diabetic Angiopathies / Q000209:etiology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D012307:Risk Factors
D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I