Diabetes, obesity, and insulin resistance in COVID-19: molecular interrelationship and therapeutic implications

Background Our understanding of the pathophysiology of the COVID-19 manifestations and evolution has improved over the past 10 months, but the reasons why evolution is more severe in obese and diabetic patients are not yet completely understood. Main text In the present review we discuss the different mechanisms that may contribute to explain the pathophysiology of COVID-19 including viral entrance, direct viral toxicity, endothelial dysfunction, thromboinflammation, dysregulation of the immune response, and the renin-angiotensin-aldosterone system. Conclusions We show that the viral infection activates an integrated stress response, including activations of serine kinases such as PKR and PERK, which induce IRS-1 serine phosphorylation and insulin resistance. In parallel, we correlate and show the synergy of the insulin resistance of COVID-19 with this hormonal resistance of obesity and diabetes, which increase the severity of the disease. Finally, we discuss the potential beneficial effects of drugs used to treat insulin resistance and diabetes in patients with COVID-19.

Automated summary

This review discusses the different mechanisms contributing to the pathophysiology of COVID-19, such as viral entrance, direct viral toxicity, endothelial dysfunction, and more. It is shown that viral infection triggers an integrated stress response, causing insulin resistance and synergizing with hormonal resistance from obesity and diabetes to worsen the severity of the disease. Additionally, the potential beneficial effects of drugs used to treat insulin resistance and diabetes in COVID-19 patients are explored.