Diabetes, obesity, and glucose control affect COVID-19 and its outcomes
Presenter: Dror Dicker, MD, Sackler School of Medicine, Tel Aviv University, Israel
Evidence-Based Medicine and COVID-19: Global Health Lessons: A Joint ACP and EFIM Session. Presented April 28, 2023
Diabetes and obesity increase the risks for hospital admission and death in individuals infected with COVID-19. The interaction between obesity, diabetes, and COVID-19 and the effect of various glucose-lowering medications on COVD-19 outcomes were reviewed by Dror Dicker, MD, Sackler School of Medicine, Tel Aviv University, Israel.
Higher body mass index (BMI) has been identified as a major risk factor for COVID-19 death, with the greatest risk observed in persons with BMI higher than 40 kg/m2. Obesity is associated with many metabolic complications, he explained. Inflammation in adipose tissue is the main cause of these complications, and this inflammation is chronic in obese individuals. Hypertrophic adipocytes in obese individuals lead to macrophage activation and production of proinflammatory cytokines and chemokines.
The level of expression of angiotensin-converting enzyme 2 (ACE2) is elevated in adipose tissue, and SARS-CoV-2 invades cells through the ACE2 receptor. As vasodilating peptides with anti-inflammatory activity, higher levels of ACE1-7, formed in the endothelial layer of human blood vessels, are desirable. SARS-CoV-2 causes a disruption in the balance of ACE1-7 and ACE2 to favor ACE2 expression, which aids SARS-CoV-2 pathogenicity.
Invasion of SARS-CoV-2 into cells leads to impaired interferon gamma, and this reduced level of interferon gamma impairs the clearance of virus from the cells, whereas high expression of interferon gamma reduces the viral expression. “People with obesity have leptin resistance, shutting down activation of interferon gamma, reducing the effectiveness of removing SARS-CoV-2 from the body,” said Dr. Dicker.
SARS-CoV-2 also leads to hypercoagulability, he said. Lower levels of antithrombin are present in people with obesity, which also promotes a higher risk for thrombosis. This is another risk factor for morbidity and mortality.
People with obesity with viral infection are more contagious than lean people, as obesity alters within-host viral population dynamics. In studies in people infected with influenza H1N1, both the amount of viral RNA shed as well as the duration of positive samples for the virus are increased in obese adults, and BMI affects the clearance of this virus from the throat. In one study, it took 21 days for H1N1-infected obese individuals to become negative by polymerase chain reaction versus 7 to 10 days in lean individuals.
People with obesity are also less immune after vaccination compared with lean subjects, with lower levels of immunoglobulin. “In SARS-CoV-2, the higher the BMI, the lower the immunoglobulins that can be produced,” he said.
A higher prevalence of type 2 diabetes is observed in individuals with severe COVID-19 symptoms. The risk of COVID-19-related mortality is nearly triple in those with type 2 diabetes compared with those without type 2 diabetes, he noted. Apart from diabetes, a high glucose level itself is a risk factor for poor outcomes in persons with COVID-19. Patients with diabetes with adequate glucose control (< 126 mg/dL) have the same risk of mortality from COVID-19 as persons without diabetes.
“People with diabetes have the same disease that COVID-19 creates,” said Dr. Dicker, noting that induction of beta cell transdifferentiation produces an abundance of glucagon rather than insulin. Further, levels of interleukin-6 (IL-6) are higher in SARS-CoV-2-infected persons, and IL-6 overexpression can cause insulin resistance and increases in glucose level.
Treatment approaches
Treatment with metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors has been shown to reduce COVID-19-related mortality relative to other antidiabetes medications. “Not surprisingly, metformin reduces inflammation and blood glucose level,” he said.
SGLT2 inhibitors reduce levels of C-reactive protein, IL-6, and ferritin in human studies, thereby decreasing systemic inflammation to limit organ damage, which may explain the favorable effect of SGLT2 inhibitors on mortality in COVID-19 patients, said Dr. Dicker.
Initially, treatment with dipeptidyl peptidase 4 (DPP4) inhibitors (also called gliptins) was thought to worsen COVID-19-related outcomes but prospective studies have shown this not to be the case.
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Disclosures
Dror Dicker, MD, reports no relationships with entities whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.