Supplementary Nitric Oxide Donors and Exercise as Potential Means to Improve Vascular Health in People with Type 1 Diabetes: Yes to NO?

Type 1 diabetes (T1D) is associated with a greater occurrence of cardiovascular pathologies. Vascular dysfunction has been shown at the level of the endothelial layers and failure to maintain a continuous pool of circulating nitric oxide (NO) has been implicated in the progression of poor vascular health. Biochemically, NO can be produced via two distinct yet inter-related pathways that involve an upregulation in the enzymatic activity of nitric oxide synthase (NOS). These pathways can be split into an endogenous oxygen-dependent pathway i.e., the catabolism of the amino acid L-arginine to L-citrulline concurrently yielding NO in the process, and an exogenous oxygen-independent one i.e., the conversion of exogenous inorganic nitrate to nitrite and subsequently NO in a stepwise fashion. Although a body of research has explored the vascular responses to exercise and/or compounds known to stimulate NOS and subsequently NO production, there is little research applying these findings to individuals with T1D, for whom preventative strategies that alleviate or at least temper vascular pathologies are critical foci for long-term risk mitigation. This review addresses the proposed mechanisms responsible for vascular dysfunction, before exploring the potential mechanisms by which exercise, and two supplementary NO donors may provide vascular benefits in T1D.