Tue Apr 19 2022

High blood sugar and suPAR levels independently worsen COVID-19 outcomes

The largest study to investigate the role of inflammatory biomarkers in hospitalized COVID-19 patients uncovers risk factors for worse health outcomes in those with diabetes.

hospitalized individuals with COVID-19 have diabetes

Researchers are uncovering why diabetes significantly raises the risk for severe COVID-19 illness. A large international study of over 2,000 hospitalized COVID-19 patients revealed that diabetes-related factors, such as elevated suPAR levels and high blood sugar, link to poorer COVID-19 outcomes.

Published in Diabetes Care, the study highlights that diabetic patients, making up about 33.5% of participants, showed higher levels of inflammatory biomarkers, worsening COVID-19’s impact. Specifically, the soluble urokinase plasminogen activator receptor (suPAR), a protein known for its association with kidney failure and heart disease, significantly influenced the severity of COVID-19 in diabetics when analyzed alongside other markers.

Key outcomes considered were in-hospital death, the requirement for mechanical ventilation, and renal replacement therapy. Salim Hayek, M.D., Alexi Vasbinder, Ph.D., R.N., and Rodica Pop-Busui, M.D., Ph.D., led the research. They also discovered that high blood sugar and increased insulin doses independently predicted more severe COVID-19 outcomes.

“One key finding from this research is that the link between diabetes and COVID-19 outcomes primarily comes from body inflammation, measured by suPAR levels,” Vasbinder stated.

The study showed that diabetics’ suPAR levels were 20.7% higher than those without diabetes.

“Yet, hyperglycemia’s effects are separate from inflammation, meaning that regardless of suPAR levels, high blood sugar or insulin doses lead to more severe COVID-19,” Busui explained. This indicates that hyperglycemia influences COVID-19 outcomes through non-inflammatory pathways, needing more research.

These insights stress the need for a collaborative approach to address the connection between diabetes and worse COVID-19 outcomes, prompting Hayek and Busui to jointly tackle high-risk factors and manage long COVID-19 at Michigan Medicine’s adult COVID-19 Long Haul Clinic.

“To better serve this high-risk group, understanding the interplay between diabetes, inflammation, and hyperglycemia in COVID-19 hospitalizations is vital,” Hayek said.

However, just knowing how these factors interact and affect COVID-19 outcomes isn’t enough for improving patient prospects.

The study suggests considering factors like age, body mass index, and race for tailored care for those at risk. Diabetic patients were generally older, more likely to be Black, and had higher BMIs.

“These patients also had nearly double the comorbidity related to hypertension, coronary artery disease, heart failure, and chronic kidney disease, connecting our initial molecular COVID studies and kidney outcomes,” noted Matthias Kretzler, M.D., a nephrologist and top kidney researcher at University of Michigan Health.

Identifying patients at the highest risk for serious COVID-19 illness involves focusing on suPAR levels, BMI, blood sugar at admission, and age, in that order. suPAR levels explained 84.2% of diabetes’ impact on COVID-19 outcomes, the study’s mediation analysis found.

“Given the study’s small number of type 1 diabetes patients, we should apply these findings to those with type 2 diabetes,” said Busui, also the recent president-elect of Medicine and Science for the 2022 American Diabetes Association Board of Directors.

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