This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education, and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.
Researchers are observing a new long-term health concern in patients hospitalized with COVID-19: an increase in new-onset high blood sugar, or hyperglycemia, lasting months after infection.
An Italian study published this month in Nature Medicine found that about half of the patients admitted to the hospital for COVID-19 during the start of the pandemic had new cases of hyperglycemia. They also had poorer outcomes from COVID-19.
“These people were not diabetic before,” said lead author Paolo Fiorina, Harvard Medical School lecturer on pediatrics, part-time, at Boston Children’s Hospital. “But during admission, about 46 percent of the patients were found to have new hyperglycemia.”
Most cases resolved. However, about 35 percent of the newly hyperglycemic patients still had high blood sugar at least six months after infection.
The study is one of the first to show that COVID-19 has a direct effect on the pancreas, said Fiorina. “It indicates that the pancreas is another target of the virus, affecting not only the acute phase during hospitalization but potentially also the long-term health of these patients.”
The study assessed the health of 551 people admitted to the hospital in Italy from March 2020 through May 2020. A follow-up period included observations through six months after hospital admission.
Compared with patients who had no signs of glucose abnormalities, the hyperglycemic patients had:
- longer hospitalizations
- worse clinical symptoms
- a higher need of oxygen
- a higher need of ventilation
- more need of intensive care treatment
“We wanted to understand the mechanism why these patients did poorly compared to those who did not have hyperglycemia,” said Fiorina, who published an earlier paper showing that COVID-19 worsens blood sugar control in people with diabetes.
Out of balance
To learn more, the researchers fitted all patients with a glucose sensor at admission. Over time, they detected many abnormalities in glucose metabolic control in the hyperglycemic patients.
They also found that hyperglycemic patients had abnormal hormone levels.
“We discovered they were severely hyperinsulinemic; they produced too much insulin,” said Fiorina.
They also had abnormal levels of proinsulin, a precursor of insulin, and markers of impaired islet beta cell function. Islet beta cells make and secrete insulin.
“Basically, the hormonal profile suggests that the endocrine pancreatic function is abnormal in those patients with COVID-19 and it persists long after recovery,” he said.
Hyperglycemic patients also had severe abnormalities in the number of inflammatory cytokines, including IL-6 and others.
“We thought that blocking IL-6, and potentially even other cytokines, would be a benefit for beta cell function,” said Fiorina.
His theory was proven true. Patients treated with anti-IL-6 therapy, tocilizumab, had greater improvement in blood sugar control compared with those who did not receive the medication.
While glucometabolic abnormalities declined over time in some patients—particularly after COVID-19 infection waned—other issues remained.
Many patients had higher blood sugar levels after eating and abnormal pancreatic hormones in the post-COVID-19 period.
The study points to the importance of evaluating pancreatic function in patients hospitalized for COVID-19, both while in the hospital and over the long term, said Fiorina.
“This goes beyond fasting glucose testing because we observed glucose metabolic abnormalities during the day which were not always present in a normal fasting test,” he said.
In terms of treatment, questions remain about how to care for patients with COVID-19-related glucose abnormalities. Should patients be treated with just an antidiabetic drug like an insulin sensitizer, or should anti-inflammatory drugs like tocilizumab and other drugs be used?
“If you keep targeting and blocking insulin, but you have a strong and chronic inflammation, it may lead to chronic damage,” said Fiorina.
He suggests larger studies need to be done to test antidiabetes and anti-inflammatory treatment.
“When you consider how many patients have been hospitalized with COVID-19, and continue to be worldwide, we may see a huge increase in the diabetic population.”
Adapted from a Boston Children's blog post.