Type 2 Diabetes Mellitus and Altered Immune System Leading to Susceptibility to Pathogens, Especially Mycobacterium tuberculosis

Abstract

There has been an alarming increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. Uncontrolled T2DM can lead to alterations in the immune system, increasing the risk of susceptibility to infections such as Mycobacterium tuberculosis (M. tb). Altered immune responses could be attributed to factors such as the elevated glucose concentration, leading to the production of Advanced Glycation End products (AGE) and the constant inflammation, associated with T2DM. This production of AGE leads to the generation of reactive oxygen species (ROS), the use of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) via the Polyol pathway, and overall diminished levels of glutathione (GSH) and GSH-producing enzymes in T2DM patients, which alters the cytokine profile and changes the immune responses within these patients. Thus, an understanding of the intricate pathways responsible for the pathogenesis and complications in T2DM, and the development of strategies to enhance the immune system, are both urgently needed to prevent co-infections and co-morbidities in individuals with T2DM.

Diabetes and COVID-19: evidence, current status and unanswered research questions

“…How diabetes increases severity of COVID-19 is unclear, though several factors may be responsible (Table 1). Poor glycaemic control impairs several aspects of the innate and adaptive immune response to viral infections and to the potential secondary bacterial infection in the lungs [6,7]. Defects in immunity namely inappropriate T-cell action, impaired natural killer cell activity and defects in complement action could reduce viral clearance [8].…”

“…Since there is no treatment currently recommended for asymptomatic people, therefore apart from isolating them, detecting these patients might not prove meaningful clinically. (7) Ethnic variations in severity of COVI19 in patients with diabetes? In the United States, the disease has caused disproportionately more fatalities in Blacks and Asians compared with Whites [44].…”

SARS-CoV 2 (Covid 19) heterogeneous mortality rate across countries may be partly explained by life expectancy, calorie intake and prevalence of diabetes.

“…However, diabetes in older age is associated with cardiovascular disease, which in itself, could help to explain the association with fatal outcomes of Covid-19 9 . Diabetic persons have poor glycemic control that impairs many aspects of the immune response to viral infection and this effect is related to cytokine pro les and to changes in immune-responses including T-cell and macrophage activation 20 . Diabetes is also known to increases the severity of Covid-19 due to a mechanism involving angiotensin-converting-enzyme 2 (ACE2), receptor for the coronavirus spike protein.…”

Host-Directed Therapies and Anti-Virulence Compounds to Address Anti-Microbial Resistant Tuberculosis Infection

“…Mycobacterium tuberculosis, the etiological agent of human tuberculosis (TB), is thought to latently infect approximately one fourth of the world's population and is responsible for over one million deaths every year [1], thus representing the leading cause of mortality by an infectious disease worldwide. Immunodeficiency caused by HIV [2] and co-morbidities like diabetes [3] constitute additional risk factors for the development of active TB disease.…”