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 diabetic complications, the beneficial effect of optimal glucose control in preventing diabetic complications is still far from being proven. In fact, such complications may not be related to glycaemic control alone.

Objective: This review summarizes several studies that suggest that a C-peptide deficiency could be new and common pathophysiology for complications in type 1 diabetes, including sexual and reproductive dysfunction.

Methods: 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 Cpeptide 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 a reduced incidence of retinopathy, nephropathy, and hypoglycaemia. Risk of vascular, hormonal, and neurologic damage in the structures supplying blood to the penis increases with increasing levels of HbA1. However, several human studies have suggested 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. C-peptide in diabetic rats improves sperm count, sperm motility, testosterone levels, and nerve conduction compared to non-treated diabetic rats.

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 have reported that C-peptide administration protects against diabetic microand macrovascular damages as well as sexual/reproductive dysfunction. Therefore, further studies are needed to confirm these promising findings.

Keywords: C-peptide; erectile dysfunction; hyperglycaemia; reproductive dysfunction; sexual dysfunction; type 1 diabetes.