C-peptide

John Wahren (Stockholm, Sweden) discussed the mechanism of action and biological role of C-peptide. He stated that C-peptide should be considered as an endogenous peptide hormone, playing an important role in the maintenance of vascular homeostasis and exerting physiological effects of importance for the prevention and treatment of type 1 diabetes. C-peptide is stored with insulin in β-cell granules, and the two are secreted in equimolecular amounts, although unlike insulin, C-peptide escapes first-pass hepatic clearance and is only cleared by the kidneys, so that circulating concentrations are ∼10 times higher than those of insulin. Wahren addressed the question of whether there is evidence of a role of C-peptide deficiency in the microvascular diseases associated with diabetes, noting that persons with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT) who maintained C-peptide in low but sustained levels showed reduced incidence of long-term complications and had greater ability to avoid hypoglycemia (1). Pancreatic or islet cell transplantation with restoration of endogenous C-peptide leads to amelioration and, in some experimental settings, to reversal of neuropathy and nephropathy.

In patients and in animal models, C-peptide corrects glomerular hyperfiltration at the onset of diabetes, reduces albuminuria, and decreases mesangial matrix expansion. C-peptide also increases sensory and motor nerve conduction velocity (NCV) in the early phase of diabetic neuropathy and ameliorates or reverses diabetes-induced nerve structural changes. C-peptide administration increases blood flow in peripheral nerve, kidney, skeletal muscle, myocardium, and skin; accelerates myocardial repolarization; increases ventricular contraction and relaxation velocities; improves stroke volume; improves erythrocyte deformability; and increases muscle glucose uptake. Wahren commented that there is no effect of C-peptide in healthy persons but only in persons with type 1 diabetes …