Can C-peptide mediated anti-inflammatory effects retard the development of microvascular complications of type 1 diabetes?

Summary Hyperglycemia is considered to be the major cause of microvascular complications of diabetes. Growing evidence highlights the importance of hyperglycemia-mediated inflammation in the initiation and progression of microvascular complications in type 1 diabetes. We hypothesize that lack of proinsulin C-peptideand lack of its anti-inflammatory properties contribute to the development of microvascular complications. Evidence gathered over the past 20 years shows that C-peptideis a biologically active peptide in its own right. It has been shown to reduce formation of reactive oxygen species and nuclear factor-κB activation induced by hyperglycemia, resulting in inhibition of cytokine, chemokine and cell adhesion molecule formation as well as reduced apoptotic activity. In addition, C-peptidestimulates and induces the expression of both Na+, K+-ATPase and endothelial nitric oxide synthase. Animal studies and small-scale clinical trials in type 1 diabetes patients suggest that C-peptidereplacement combined with regular insulintherapy exerts beneficial effects on kidney and nerve dysfunction. Further clinical trials in patients with microvascular complications including measurements of inflammatory markers are warranted to explore the clinical significance of the aforementioned, previously unrecognized, C-peptideeffects. Copyright © 2013 John Wiley & Sons, Ltd.