A group of researchers is currently observing a new long-term health problem in hospitalized patients with COVID-19 that could cause a wave of diabetes: an increase in new onset hyperglycemia lasting months after infection.
An Italian study showed that about half of the subjects hospitalized for COVID-19 during the onset of the pandemic she had new cases of hyperglycemia – high blood sugar levels. They also had worse results.
The Research was published on Nature Metabolism.
Wave of Diabetes Coming and Covid19: Are They Really Related?
“These people weren’t diabetic before“Says the lead author Paolo Fiorina, MD, Ph.D., affiliated with the Division of Nephrology at the Boston Children’s Hospital. “But during hospitalization, about 46 percent of patients were found to have new hyperglycemia. “ Although most of the cases have resolved, about 35 percent of new hyperglycemic patients remained hyperglycemic at least six months after infection.
The study looked at the health of 551 people hospitalized in Italy from March to May 2020. A follow-up period included six months after hospital admission.
Compared to patients with no signs of glycemic abnormalities, hyperglycemic patients also had worse clinical problems:
- Longer hospitalizations;
- Worse clinical symptoms;
- A greater need for oxygen:
- An increased need for ventilation:
- More need for intensive care;
“We wanted to understand the mechanism by which these patients fared poorly compared to those who did not have hyperglycemiaSays Fiorina, who published a previous document showing the worsening of metabolic glucose control of COVID-19 in diabetics. To try to better understand this dynamic, all patients were equipped with a glucose sensor upon admission. Over time, researchers have found many abnormalities in the metabolic control of glucose in hyperglycemic patients.
The study found that hyperglycemic patients had abnormal hormone levels. “We found that they were severely hyperinsulinemic; produced too much insulin “, Fiorina states. They had also abnormal levels of proinsulin, an insulin precursor, and markers of altered islet beta cell function. Islet beta cells produce and secrete insulin.
“Basically, the hormonal profile suggests that pancreatic endocrine function is abnormal in those patients with COVID-19 and persists long after recovery “, he claims. Hyperglycemic patients presented also severe abnormalities in the amount of inflammatory cytokines, including IL-6 and others.
“We thought that blocking IL-6, and potentially other cytokines as well, would be an advantage for beta cell function “, adds Fiorina, whose theory has proved true. Patients treated with anti-IL-6 therapy (tocilizumab), had greater improvement in glycemic control than those who did not receive the drug.
While glucometabolic abnormalities declined over time in some patients, particularly after COVID-19 infection, others remained. Many patients had higher postprandial (after eating) glucose levels and abnormal pancreatic hormones in the post-COVID-19 period.
“This study is one of the first to show that COVID-19 has a direct effect on the pancreas”says Fiorina. “It indicates that the pancreas is another target of the virus that affects not only the acute phase during hospitalization, but potentially also the long-term health of these patients ”.
The study underscores the importance of assessing pancreatic function in patients admitted to hospital for COVID-19, during hospitalization and in the long term. “This goes beyond the fasting glucose test because we observed metabolic glucose abnormalities throughout the day that weren’t always present in a normal fasting test.“, Fiorina states.
In terms of treatment, questions remain about how to care for patients with COVID-19-related glycemic abnormalities. Should patients only be treated with an antidiabetic drug such as an insulin sensitizer or should anti-inflammatory drugs such as tocilizumab and other drugs be used?
“If you keep targeting and blocking insulin, but you have an inflammation strong and crobica, can lead to chronic damage“, Says Fiorina, which suggests that larger studies are needed to test antidiabetic and anti-inflammatory treatment. “If you consider how many patients have been hospitalized with COVID-19 and continue to be all over the world, we could see a huge increase in the diabetic population ”.
Wave of diabetes coming and covid19: first doubts in the spring of 2020
Previously it had been observed, in the spring of 2020, by a group of experts from New York that a significant number of patients had a high amount of blood sugar.
“My colleague and I were having a hard time keeping blood sugar levels under control in some covid19 patients even in those who did not have a history of diabetes”, the biologist had explained Shuibing Chen, stem cell expert at the Weill Cornell Medicine. “Even more surprising “, Chen continues, “it was the fact that some patients, who did not suffer from this disease prior to infection, developed diabetes after being cured of COVID-19 ”.
A global analysis carried out also in 2020 by the health researcher Thirunavukkarasu Sathish at the McMaster University in Canada found that nearly 15% of individuals who had contracted a severe covid19 signature had unfortunately also developed diabetes. But, specify, “This number is probably higher among individuals at greater risk, for example, those with prediabetes.”
Peter Jackson, biochemist at the Stanford University School of Medicine, estimated that “the percentage of patients with severe COVID-19 who can develop diabetes reaches 30% “
The possibility that there was a link between covid19 and diabetes prompted experts Chen and Jackson to undertake independent investigations to understand how SARS-CoV-2 could trigger hyperglycemia: “Their findings offer essential information on the underlying mechanisms by which COVID-19 can lead to the development of new cases of diabetes in infected patients “ he claims Rita Kalyani, associate professor of medicine in the Division of Endocrinology, Diabetes and Metabolism of the Johns Hopkins University, not involved in either study.
In a previous study, Chen’s team cultured different types of tissue in the lab to see which ones were vulnerable to the COVID-19 virus. “To our great surprise, we found that pancreatic beta cells are very permeable to SARS-CoV-2 infection.”Said Chen.
The pancreas, located behind the stomach, is a complex organ made up of numerous types of cells that aid in digestion. It contains beta cells that produce insulin, the hormone that supplies sugar molecules from the blood to the body’s cells where they are used for energy.
However, the fact remains that a virus that can infect cells grown on a laboratory slide is not necessarily capable of attacking the organism in the same way. To test whether the lab observations represented what actually could occur in a human body, both Chen and Jackson’s groups used autopsy samples from covid19 dead subjects: both groups detected SARS-CoV-2 in the pancreatic beta cells of deceased patients.
But how does it use a respiratory virus to migrate from the lungs and reach the pancreas? A time As patients become infected with pneumonia, infection of the lower lobe of the lung can cause tissue damage that allows the virus to escape from the pulmonary alveoli and reach the blood vessels, Jackson explains.
“Once it has entered the circulatory system, the virus can penetrate other highly vascularized tissues such as the pancreas, brain and kidneys ”. Others believe that the virus can enter the circulatory system from the intestine, which can occur in patients without healthy intestinal flora.
In both studies it was observed that beta cells infected with SARS-CoV-2 stop producing insulin. In Jackson’s study, infected beta cells die from apoptosis, a genetically programmed self-destruct sequence activated by damaged cells.
Chen’s team instead observed that infected beta cells undergo a process called transdifferenziazione, that is to say they convert to another type of cell, a type that no longer produces insulin. It is possible that some of the infected beta cells will undergo the transdifferenziazione while others self-destruct.
In both cases, the result is the same: when covid19 attacks pancreatic beta cells, insulin production is reduced.
This situation can cause type 1 diabetes which is typically caused by genetic risk factors that stimulate an autoimmune reaction that attacks and destroys beta cells. Type 1 diabetes is diagnosed more frequently at a young age, and patients have to self-administer insulin every day as their body is no longer able to produce it. Not only that, type 1 diabetes occurs as a result of a triggering environmental factor, such as an infection, which activates the immune reaction.
On the other hand, as regards type 2 diabetes, which is much more common, it develops when the body becomes resistant to the insulin it produces. Type 2 diabetes can be controlled by paying particular attention to nutrition and physical activity. Under certain circumstances it will be necessary to complete the treatment with specific drugs that improve insulin sensitivity.
It is important to continue analyzing the infected beta cells and their fate because they might to be tracked down systems to prevent their destruction in subjects with severe cases of COVID-19. Chen’s study group conducted their studies on a wide range of chemicals in the hopes of finding one that could avoid the transdifferentiation process.