Insulin, corticosteroids may produce additive anti-inflammatory effect in severe COVID-19

ByRegina Schaffer

A combination of anti-inflammatory and antithrombotic actions induced by IV insulin infusion could provide “potent inhibition” of the effects of COVID-19 in hospitalized patients, according to a new review published in Diabetes Care.

“Steroids are not ‘clean’ anti-inflammatory agents,” Paresh Dandona, MD, PhD, an Endocrine Today Editorial Board Member, SUNY distinguished professor and chief of endocrinology in the department of medicine at the University of Buffalo, New York, told Healio. “At higher concentrations, they will cause pro-inflammatory effects. Our data show that if you combine high doses of steroids with insulin, insulin takes away the pro-inflammatory effect of the steroid. In combination, you have a very nice, additive, potent mixture.”

Dandona is an *Endocrine Today* Editorial Board Member, SUNY distinguished professor and chief of endocrinology in the department of medicine at the University of Buffalo, New York.

Obesity and type 2 diabetes are both characterized by chronic inflammation, ultimately leading to an inability to generate adequate immunologic responses to specific infections like COVID-19, Dandona and Husam Ghanim, PhD, research associate professor at the Jacobs School of Medicine at the University of Buffalo, wrote in the review.

“The two major risk factors determining morbidity and mortality that have emerged consistently from the patterns of clinical manifestations in COVID-19 infection are obesity and diabetes, with and without hyperglycemia,” Dandona and Ghanim wrote. “Both diabetes and obesity are characterized by chronic inflammation that impairs the ability to generate specific immunological responses to infections and antigenic challenges. Hyperglycemia also induces inflammation and impairs the defense mechanisms necessary for combating infection.”

Despite insulin resistance associated with these states, an IV insulin infusion induces an anti-inflammatory effect within 2 hours, Dandona said.

“Insulin is also able exert an additive anti-inflammatory action with corticosteroids while simultaneously neutralizing the paradoxical proinflammatory action of the high doses of corticosteroids,” Dandona and Ghanim wrote. “In addition, insulin has an antiaggregatory effect on platelets and an antithrombotic and a profibrinolytic action. This combination of actions could provide a potentially potent inhibition of the effects of COVID-19.”

In the review, Dandona and Ghanim wrote that IV insulin in combination with dexamethasone for all patients in the ICU could potentially improve clinical outcomes and should be investigated further.

“Glucose is pro-inflammatory and any inflammation will cause an increase in glucose,” Dandona told Healio. “Therefore, glucose will amplify the inflammatory effect. If you break that cycle by infusing insulin, insulin has its own anti-inflammatory response. In addition, it suppresses glucose, so any glucose increase is neutralized, and you have a combined action.”

Dandona added that in a recent study, also published in Diabetes Care, Raffaele Marfella, MD, PhD, of the department of advanced medical and surgical sciences at the University of Campania in Naples, Italy, and colleagues demonstrated that diabetes and hyperglycemia are associated with a marked increase in mortality among inpatients with COVID-19, whereas IV insulin therapy in patients with COVID-19 reduced mortality.