Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports

Abstract

Alzheimer’s disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.

SGLT2 Inhibitors in COVID-19: Umbrella Review, Meta-analysis, and Bayesian Sensitivity Assessment

“…The Umbrella review part of our study comprised 10 reviews: one systematic review of case reports 79 , six systematic reviews and meta-analyses 7,8,[80][81][82][83] , one meta-analysis 84 , and two network meta-analyses 4,57 .…”

“…It was also noted that there was a decreased risk of hospitalisation 54 and a reduced risk of requiring non-invasive or invasive mechanical ventilation 61 . While a review of case reports suggested a possible increase in the risk of euglycemic diabetic ketoacidosis 79 with SGLT2i, the level of evidence was deemed non-signi cant.…”

“…83 . The reviews mostly fell into Class III 4,8,81,83 and Class IV 7,57,80,82,84 levels of evidence, with one review deemed non-signi cant 79 . Our analysis of both observational studies and trials showed no signi cant increase in the odds of developing DKA.…”

“…The review population consisted of patients with T2DM who contracted COVID-19 and were on SGLT-2 inhibitors either before or after their hospitalisation or the onset of infection. The reviews primarily assessed outcomes such as the severity of COVID-19 infection 7,80,82 , need for Intensive Care Unit (ICU) admission, invasive and non-invasive mechanical ventilation 4,7,8,80,82 , Disseminated Intravascular Coagulation (DIC) 82 , Euglycemic Diabetic Ketoacidosis (Eu-DKA) 79,81,83 and in-hospital Mortality 4,7,8,57,[80][81][82][83][84] .…”