key: cord-0078423-f9rjafv4
authors: Ghosh, Rajdeep; Basak, Ullash; Ghosh, Debasish; Sarkar, Joy
title: Drug-induced diabetes and hepatoxicity in COVID-19 patients
date: 2022-05-22
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2022.102514
sha: 79eec3f7957e793216bf161a3553c94a9d8297b5
doc_id: 78423
cord_uid: f9rjafv4

nan

Keywords: COVID-19; Diabetes; Drug toxicity; Hepatoxicity; Corticosteroid Dear Editor, COVID-19, a newly found diabetes-related health risk, has been linked to diabetic ketoacidosis and drug-related liver disorders. SARS-CoV-2 may cause pleiotropic changes in glucose metabolism, which could exacerbate the pathophysiology of pre-existing diabetes or lead to new disease processes. In COVID-19 treatment, physicians often use glucocorticoid drugs such as methylprednisolone and dexamethasone to control the inflammatory changes during COVID-19 and prevent the severity. Corticosteroids stimulate endogenous glucose production, promote gluconeogenesis, and antagonize insulin's metabolic functions. They also increase the effects of other counterregulatory hormones, like glucagon and adrenaline, which stimulate endogenous glucose synthesis. It has also been demonstrated that the nuclear receptor peroxisome proliferator-activated receptor is required for the increase in endogenous glucose synthesis generated by corticosteroids. Corticosteroids inhibit peripheral glucose absorption in muscle and adipose tissue. Corticosteroids also reduce insulin synthesis and secretion from pancreatic β-cells, causing β-cell failure indirectly through lipotoxicity [1] . Normoglycemic individuals with decreased insulin sensitivity and insulin production at a low rate prior to steroid use who develop hyperglycemia as a result of the steroids they take (Fig. 1) [2] .

Corticosteroids, which are produced from cholesterol metabolism, have the ability to disrupt numerous components of the body's glucose homeostasis. These compounds must be assessed since they alter liver metabolism and steatosis [3] .

Various studies show drug-induced liver injury coupled with COVID-19 therapy.

According to one study, more than half of the COVID-19 patients who had normal liver function indicators when they arrived had abnormal liver function markers one week later [4] .

As per the randomized clinical trials lopivir-ritonavir treatment has been linked to increased AST, ALT, and bilirubin levels [5] , whilst remdesivir has only been linked to elevated AST and ALT levels in both treated and control groups [6] [7] [8] . Additionally, the use of acetaminophen and hydroxychloroquine has been associated to abnormal liver markers [6, 9] .

Furthermore, the WHO safety report database clearly demonstrates that remdesivir use is associated with a statistically significant risk of liver damage [10] The combination of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors causes J o u r n a l P r e -p r o o f increased liver enzymes [5] Another study of 1,040 COVID-19 patients recently revealed that 22.6 percent of the participants had elevated ALT/AST levels [11] . The tocilizumab medication group had a significantly higher ALT rise in the retrospective investigation of observational cohort analysis [12] . Favipiravir, an oral broad-spectrum, acting as an inhibitor of viral RNAdependent RNA polymerase, causes cholestatic liver damage in those with ALD-related liver disease.

There are no financial and non-financial conflicts of interest.

Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review

Novel insights into glucocorticoid-mediated diabetogenic effects: Towards expansion of therapeutic options?

Dexamethasone in the era of COVID-19: Friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes

Clinical Features of COVID-19-Related Liver Functional Abnormality

COVID-19: abnormal liver function tests

Update alert 3: Hydroxychloroquine or chloroquine for the treatment or prophylaxis of COVID-19

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

Remdesivir for the Treatment of Covid-19 -Final Report

Clinical and Research Information on Drug-Induced Liver Injury 2020. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Disease

Hepatic Disorders With the Use of Remdesivir for Coronavirus

Liver injury is independently associated with adverse clinical outcomes in patients with COVID-19

Tocilizumab in patients with severe COVID-19: a retrospective cohort study

Debasish Ghosh Vishwanath Ayurved Mahavidyalaya and Hospital