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

Abstract

Background The disclosure in the media of a benefit with the use of dexamethasone in patients with COVID-19 infection sets precedents for self-medication and inappropriate use of corticosteroids. Methods This is a critical interpretive synthesis of the data available in the literature on the effects of the use of corticosteroids and the impact that their indiscriminate use may have on patients with diabetes. Reviews and observational and experimental studies published until June 18, 2020 were selected. Results Corticosteroids are substances derived from cholesterol metabolism that interfere with multiple aspects of glucose homeostasis. Interactions between corticoid receptors and target genes seem to be among the mechanisms responsible for the critical functions of glucocorticoids for survival and anti-inflammatory effects observed with these medications. Corticosteroids increase hepatic gluconeogenesis, reduce peripheral use of glucose and increase insulin levels. Previous studies have shown that glucocorticoids have a pro-adipogenic function, increasing deposition of abdominal fat, and lead to glucose intolerance and hypertriglyceridemia. In addition, these drugs play a role in controlling liver metabolism and can lead to the development of hepatic steatosis. Glucocorticoids reduce the recruitment of osteoblasts and increase the number of osteoclasts, which results in increased bone resorption and greater bone fragility. Moreover, these medications cause water and sodium retention and increase the response to circulating vasoconstrictors, which results in increased blood pressure levels. Chronic or high-dose use of corticosteroids can, by itself, lead to the onset of diabetes. For those who were already diagnosed with diabetes, studies show that chronic use of corticosteroids leads to a 94% higher risk of hospitalization due to diabetes complications. In addition to the direct effects on glycemic control, the effects on arterial pressure control, lipids and bone metabolism also have a potential for severe consequences in patients with diabetes. Conclusion Fear and uncertainty toward a potentially serious infection may lead people to self-medication and the inappropriate and abusive use of corticosteroids. More than ever, it is necessary for health professionals to be alert and able to predict damages related to the use of these drugs, which is the first step to minimize the potential damages to come.

Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

“…However, the same trial found that there was a modest detrimental effect in patients not receiving respiratory support, again highlighting the importance of appropriate balance in the inflammatory response to COVID-19. In patients with diabetes, corticosteroids can have an impact on glycaemic control and other metabolic parameters and their use should be under careful clinical review ( 303 ).…”

Target SARS-CoV-2: computation of binding energies with drugs of dexamethasone/umifenovir by molecular dynamics using OPLS-AA force field

“…This emphasizes the presence of strong interactions between (SARS-CoV-2 + dexamethasone). The output of literature survey over clinical trials of umifenovir (Lian et al 2020;Vankadari 2020;Choudhary and Silakari 2020;Costanzo et al 2020;Zhang et al 2020;Kadam and Wilson 2017;Valle et al 2020)/dexamethasone (Ortolani and Pastorello 2020;Li and De Clercq 2020;Mittal et al 2020;Ledford 2020; Low-cost dexamethasone 2020; WHO welcomes preliminary Alessi et al 2020;Cain and Cidlowski 2020;Lammers et al 2020;Stauffer et al 2020) on SARS-CoV-2 infected patients also suggests that dexamethasone is the best and the first approved referral drug in UK, Australia, and South Africa countries for the treatment of COVID-19 infection. Thus, dexamethasone is one of the best-repurposed drugs to bind SARS-CoV-2 over umifenovir.…”

Status of Novel Coronavirus Disease 2019 (COVID-19) and Animal Production

“…Based on positive results, dexamethasone has been authorized by the UK government for the treatment of critically ill COVID-19 patients (53). However, the comorbidity factors (especially diabetes) should be considered before treatment because some researchers reported that dexamethasone increases the risk of COVID-19 progression to severe disease, especially in patients with diabetes (54,55).…”