Type 2 diabetes and viral infection; cause and effect of disease

Abstract

The recent pandemic of COVID-19 has made abundantly clear that Type 2 diabetes (T2D) increases the risk of more frequent and more severe viral infections. At the same time, pro-inflammatory cytokines of an anti-viral Type-I profile promote insulin resistance and form a risk factor for development of T2D. What this illustrates is that there is a reciprocal, detrimental interaction between the immune and endocrine system in the context of T2D. Why these two systems would interact at all long remained unclear. Recent findings indicate that transient changes in systemic metabolism are induced by the immune system as a strategy against viral infection. In people with T2D, this system fails, thereby negatively impacting the antiviral immune response. In addition, immune-mediated changes in systemic metabolism upon infection may aggravate glycemic control in T2D. In this review, we will discuss recent literature that sheds more light on how T2D impairs immune responses to viral infection and how virus-induced activation of the immune system increases risk of development of T2D.

Keywords: Antidiabetic drugs; COVID-19; Corona virus; Diabetes; Diabetes mellitus type 2; Immune defects; Immune system; Immunometabolism; Infection; Insulin resistance; T2D; Viral infection.

Fig. 1

Negative impacts of T2D on immunological control of viral infection.

Fig. 2

Pro-diabetic effects of viral infection. Viral infection activates a Type-I immune response, resulting in the production of cytokines such as TNF, IFNγ and IL-6. These induce transient insulin resistance in muscle and liver. The pancreas compensates IR through increased secretion of insulin, which directly promotes the antiviral immune system. In obesity, cytokine-induced IR can contribute to the formation of IR. In addition, several viruses infect the pancreas, which negatively impacts its ability to produce insulin. This may also contribute to loss of pancreatic β-cell function.