Diabetes, Obesity, COVID-19, Insulin, and Other Antidiabetes Drugs

Coronavirus disease 2019 (COVID-19) viral infection, like other infections, triggers an inflammatory response that is usually confined to the respiratory system.However, there is evidence that in a full-blown case, almost all systems of the body may be involved.In addition, there is the syndrome of cytokine storm, characterized by severe systemic inflammation and a massive release of proinflammatory cytokines (1).It is well established that obesity and diabetes are major risk factors for COVID-19 infections and that the morbidity and mortality in association with these conditions is markedly increased.Since both obesity and diabetes are associated with chronic inflammation, it is likely that the inflammatory response to COVID-19 in such patients is affected by the background of chronic inflammation.This review aims to elucidate some of these processes and potential strategies to combat them. CHRONIC INFLAMMATORY STATES OF OBESITY AND DIABETESThe concept that obesity is associated with inflammation was initiated with the cardinal work of Hotamisligil et al. ( 2), which demonstrated that the proinflammatory cytokine tumor necrosis factor-a (TNF-a) was expressed in the adipose tissue and that its expression was markedly elevated in the ob/ob mouse.In addition, this increase was associated with insulin resistance.Neutralization of TNF-a with the infusion of soluble TNF-a receptor resulted in the reversal of insulin resistance in the ob/ob mouse.These remarkable observations resulted in the understanding that obesity is a state of chronic inflammation and that inflammatory mediators may contribute to the pathogenesis of insulin resistance.The same group then demonstrated that human adipose tissue also expresses TNF-a and that its expression is increased in obesity (3).Another research group simultaneously confirmed this observation (4).This observation was followed by the demonstration that plasma concentration of TNF-a was significantly elevated in obese humans and that TNF-a fell after weight loss (5).A more comprehensive description of inflammation in obesity and its relationship to insulin resistance was demonstrated by the work of Ghanim et al. (6,7).These features were then linked to the metabolic syndrome (8).These observations were further supported by the fact that human obesity was associated with chronic oxidative stress and that dietary restriction and weight loss led to a marked reduction in the indices of oxidative stress even over a short period of 4 weeks (9).These observations were confirmed by an article from Japan (10).Oxidative stress is known to trigger inflammatory processes and often occurs concomitantly with inflammation.The occurrence of inflammation in association with type 2 diabetes was first demonstrated by Pickup and Crook (11,12).These articles emphasize the increase in acute phase reactants to inflammation in patients with type 2 diabetes, including sialic acid and cytokines IL-6 and TNF-a in particular.