The role of IGF-1 resistance in obesity and type 2 diabetes-mellitus-related insulin resistance and vascular disease.

IMPORTANCE OF THE FIELD: The insulin-resistant conditions of type 2 diabetes mellitus (T2DM) and obesity are a major cause of cardiovascular disease on a global scale. These disorders are not only a cause of ill health but are a huge financial drain on healthcare systems. T2DM leads to an increased risk of cardiovascular mortality equivalent to over 10 years of ageing while obesity independent of T2DM also leads to a substantially increased risk of acute myocardial infarction. Recent trials of therapeutic agents and approaches to preventing the cardiovascular complications of type 2 diabetes have been disappointing. AREAS COVERED IN THIS REVIEW: The role of insulin resistance in the endothelium in the regulation of the anti-atherosclerotic signalling molecule NO and a potential important role for IGF-1 in vascular NO production. WHAT THE READER WILL GAIN: A comprehensive understanding of how insulin and IGF-1 regulate vascular function and the effect of type 2 diabetes on these pathways. TAKE HOME MESSAGE: The roles of insulin and IGF-1 in vascular function are complex and intimately related. Nevertheless IGF-1 signalling in the arterial wall has the potential to be manipulated to protect the vasculature against the development of atherosclerosis and its devastating complications.