Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia

Abstract

Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.

Keywords: COVID-19; diabetes; hyperglycemia; immune system; infections.

Figure 1

Illustration of a hypothetical outcome in an experimental model of bacterial pneumonia in normal conditions vs. during hyperglycemia. Under normoglycemia conditions the immune response handles successfully bacterial infections. Nevertheless, hyperglycemia impairs the immune response by inducing several glucose-related factors, including those mentioned above. These scenarios could determine the outcome during bacterial infections.

Figure 2

Development of a vicious cycle induced by a stressful lifestyle. Stressors promote the behavior of hypercaloric food binge which, in turn, increases the release of catecholamines and cortisol (immunosuppressants). Subsequently, catecholamines induce glycolysis, reinforce the maladaptive eating patterns, and negatively modulate immune cell activity. On the other hand, cortisol induces chronic immunosuppression.