C-peptide as a mediator of lesion development in early diabetes--a novel hypothesis

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Various risk factors such as hypertension, dyslipidemia, and a proinflammatory and prothrombotic state contribute to atherogenesis in this high-risk population, but the pathophysiologic mechanisms leading to this characteristic pattern remain largely unexplored. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential relevance of such C-peptide effects on atherogenesis in diabetic patients.