The Potential Role of C-peptide in Sexual and Reproductive Functions in Type 1 Diabetes Mellitus: An Update

Abstract

Background: Although hyperglycaemia is known to be the leading cause of the diabetic complications, the beneficial effect of an optimal glucose control on the prevention of diabetic complications is still far from being proven. In fact, such complications may not to be related to glycaemic control alone. Objective: This review summarizes several studies that suggest that a C-peptide deficiency could be a new and common pathophysiology for complications in type 1 diabetes including sexual and reproductive dysfunction. Method: We reviewed in vitro, in vivo and human studies on the association between C-peptide deficiency or C-peptide replacement therapy and complications in type 1 diabetes. It seems that C-peptide replacement therapy may interrupt the connection between diabetes and sexual/reproductive dysfunction. Results : The Diabetes Control and Complications Trial suggested that maintaining C-peptide secretion is associated with reduced incidence of retinopathy, nephropathy and hypoglycaemia. Risk of vascular, hormonal and neurologic damage in the structures supplying the penis increases with increasing levels of HbA1. However, several human studies suggested that there is an association between C-peptide production and hypothalamic/pituitary functions. When exposed to C-peptide, cavernosal smooth muscle cells increase the production of nitric oxide. Compared with non-treated diabetic rats, C-peptide in diabetic rats improves sperm count, sperm motility, testosterone levels, and nerve conduction. Conclusion: C-peptide deficiency may be involved, at least partially, in the development of several pathological features associated with type 1 diabetes including sexual/reproductive dysfunction. Preliminary studies reported that C-peptide administration protects against diabetic micro- and macrovascular damages as well as sexual/reproductive dysfunction. Therefore, further studies are now needed to confirm these promising findings.