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.
Highlights
Diabetes mellitus is a chronic and complex illness characterized by several metabolic alterations including dyslipidemia and hyperglycemia, among others [1]
The restoration of normoglycemia seems to be related to a better prognosis for bacterial infections [5]; whereas in COVID-19 diabetic patients, no obvious conclusions have been reached about the impact of normoglycemic treatments on the development and outcome of this particular disease [8]
To consider the relevant literature in this theoretical review, we searched for studies published in various databases such as Science direct, Pubmed central and Google Scholar. These databases included any combination of the main key terms “bacterial infections,” “COVID-19,” “diabetes,” “influenza A virus,” “hepatitis B and C viruses,” “human immunodeficiency virus,” and “hyperglycemia” among themselves and with important topics such as: “rheological properties of blood,” “biochemical alterations of diabetic immune cells,” “immune response on hyperglycemic environment,” “hypoglycemic drugs,” “bacterial infection outcome,” and “comorbidities with COVID19.”
Summary
Diabetes mellitus is a chronic and complex illness characterized by several metabolic alterations including dyslipidemia and hyperglycemia, among others [1]. As anorexia is an important stereotypic behavior of the sickness response, it could be an adaptive strategy for combating some infectious illnesses In this sense, it has been reported that bacteria from other groups (e.g., Salmonella) may induce inhibition of anorexia via Salmonella leucine rich repeat protein (SlrP) which inhibits interleukin-1β (IL-1β). Very few reports have analyzed the appropriate management of glycemia according to the infection type, immunological responsiveness, and clinical variables (i.e., patient age, time or period elapsed with diabetes, etc.) To focus on these aspects, the present review has considered information on: (i) the effect of glycemia on infection outcome and immune cells physiology; (ii) the biochemical alterations in cell physiology during diabetes and/or hyperglycemia; and (iii) the impact of pharmaceutical care interventions for glycemia control on some of the most frequent emerging infectious diseases
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