Since the early days of the pandemic, it has been well documented that people living with diabetes who contract COVID-19 are at increased risk of developing severe illness and even long COVID. But recent studies have suggested that contracting the virus may also increase the risk of developing diabetes.
The SARS-CoV-2 virus that causes COVID-19 affects people in different ways. Though it was initially thought to be a respiratory virus, as the pandemic progressed it became apparent it was able to adversely affect different parts of the body beyond the lungs, increasing the risk of chronic health problems. Many doctors who were treating COVID-19 patients in the early stages of the pandemic reported having trouble managing their blood sugars, even when the patients were not diabetic. Because it was thought to be mainly a respiratory virus, the rising blood sugars in non-diabetic patients left many clinicians wondering why this was happening. A study published in late 2020 showed that nearly 15 percent of patients with severe COVID-19 went on to develop diabetes. This is likely an underestimate, as subsequent studies have shown much higher proportions of patients with severe COVID-19 later getting the disease, with one Stanford University paper estimating as many as 30 percent may go on to develop diabetes.
Another study looking at the health of veterans showed an increase in the risk of males specifically developing diabetes after being infected with SARS-CoV-2. Almost all cases detected were Type 2 diabetes, in which the body becomes resistant to or does not produce enough insulin. The study showed male veterans who had recovered from COVID had a 40 percent increased risk of subsequently being diagnosed with diabetes, though it stopped short of saying COVID caused diabetes. It is also worth noting that veterans may not be representative of a population, as they can suffer significant hardships that can affect their physical and mental health and put them at increased risk of long-term conditions.
Nevertheless, it is not just in adults that the link between SARS-CoV-2 and diabetes has been made. In January 2022, the United States Centers for Disease Control and Prevention (CDC) published the results of a study spanning 15 months. It looked at the risk of people under age 18 developing any type of diabetes, 30 days or more after contracting COVID-19. They compared this with a group of individuals of a similar age who did not contract the virus during the same period as well as a second control group that contracted other respiratory viruses before the pandemic. The study found that those with COVID-19 were 166 percent more likely to develop diabetes 30 days or more after infection when compared to those who did not have COVID-19, and 116 percent more likely to get diabetes when compared to those who had other respiratory viruses before the pandemic.
It is important to understand the link between COVID-19 and diabetes for a number of reasons. Doctors need to know to monitor blood sugar levels in patients they are caring for and that they may be at risk of hyperglycaemia (high blood sugars) even though they may not have diabetes. It is also vital to know whether these same patients will need therapeutics in the form of insulin or other medication to manage their blood sugar levels.
Blood sugars and the pancreas
But to understand all this, we need to know how COVID-19 can cause diabetes, which is a chronic (long-lasting) health condition that affects how your body turns food into energy. Most of our food is broken down to release sugars or glucose into our bloodstream. When blood sugars become too high, an organ known as the pancreas secretes a hormone – insulin – which takes the sugar out of the blood and moves it into our cells so they can use it for energy and to carry out their daily functions. If you have diabetes, your body either doesn’t make enough insulin or cannot use the insulin it makes as well as it should. When there isn’t enough insulin or cells stop responding to insulin, too much blood sugar stays in your bloodstream. Over time, that can cause serious health problems, such as heart disease, vision loss and kidney disease.
Research has shown that SARS-CoV-2 can impact the pancreas and blood sugars in several ways. Scientists have known for some time that the virus enters human cells using receptors called angiotensin I-converting enzyme type 2 (ACE2) receptors. The cells of the pancreas that make insulin are known as beta cells. At the beginning of the pandemic, it was not known whether pancreatic beta cells expressed ACE2 receptor cells for the virus to bind to and enter. But using cutting-edge technology, a team of scientists showed that ACE2 receptors were widely distributed along the pancreas, including its beta cells, allowing for a mode of entry for the SARS-CoV-2 virus. The pancreas, being a vital organ, has a generous blood supply and it wouldn’t take long for the virus to enter it from the lungs via the bloodstream.
Once inside the beta cells of the pancreas, the virus can change and even kill the cells so that they stop producing insulin. One study found that infected beta cells changed their behaviour, in that they stopped producing insulin altogether – a process known as transdifferentiation. Another study found that once pancreatic beta cells were infected by SARS-CoV-2, they underwent a process of self-destruction known as apoptosis, which occurs in injured or infected cells to help reduce the risk of infection spreading to other healthy cells. Both these processes lead to a radical reduction in insulin production, without which blood sugars would increase. A lack of insulin production due to beta-cell failure is what happens in Type 1 diabetes, usually seen in young people; this is a similar picture.
Another mechanism by which COVID-19 can elevate blood sugars and cause hyperglycaemia is through its ability to cause widespread inflammation throughout the body and increase the risk of insulin resistance. Post-mortem findings of those who have succumbed to COVID-19 have revealed evidence of inflammation including large numbers of inflammatory cells found in the heart, lungs, blood vessels and brain. This is thought to be due to the immune system overreacting to the virus and not being able to turn itself off. This large burden of inflammatory cells can affect the functions of skeletal muscle and the liver, both of which play important roles in detecting levels of glucose and requirements of insulin for the body.
There has to be a careful balance between levels of insulin and blood sugars. If there is not enough insulin then blood sugars remain high, but conversely, if the pancreas is overproducing insulin and floods the body with the hormone, this too can make cells unresponsive to its effects – a process known as insulin resistance.
High levels of inflammation in the body have been linked to insulin resistance as the pancreas overproduces insulin during states of inflammation; this means insulin is being produced but cells are not responding to it, so blood sugars remain high. This is akin to Type 2 diabetes, where insulin resistance is the main mechanism of action that leads to higher blood sugars.
One of the most useful medications we can give patients who have severe COVID-19 is steroids, such as dexamethasone. Steroids, while important in treating the overreaction of the immune system, can increase insulin production by the pancreas to such a level that cells stop responding to it – another form of insulin resistance and subsequent high blood sugars.
Diabetes and COVID
The double whammy in all this is that multiple studies have shown that those living with any type of diabetes are at increased risk of becoming seriously ill should they contract COVID. In fact, a recent study showed they were up to three times more likely to be critically or severely ill compared to those without diabetes should they contract COVID. With re-infections being an ongoing issue, developing diabetes as a possible consequence of COVID will then put these people at risk of becoming seriously ill should they get it again. The best protection for them, aside from mitigations from avoiding getting infected, is trying to get the best possible control of their blood sugars, as it is high blood sugars and subsequent high levels of insulin that lead to many of the complications.
There are, of course, scientists who remain unconvinced about the link between COVID-19 and diabetes, saying that those most likely to develop high blood sugars during infection and onwards are likely to have been at high risk of developing diabetes anyway, and the infection simply pushed them over the edge. This is similar to what is seen in pregnant women who develop gestational diabetes (diabetes in pregnancy); they are usually women with risk factors such as being of certain ethnicities, having a family history of the illness, or being overweight. Although they remain at high risk of diabetes after birth and need monitoring, many return to normal blood sugar levels without the need for further treatment after the baby is born.
We do not know the long-term effects of diabetes triggered by a COVID-19 infection, but one study showed a third of the people who had new high blood sugar levels during a coronavirus infection remained that way for at least six months after their recovery. It may be that the SARS-CoV-2 virus also affects the other functions of the pancreas, such as its role in producing digestive enzymes.
Data is being collected by a team at King’s College London to try and understand the broader implications of COVID-19 and the pancreas. It has long been suspected – though never proven – that Type 1 diabetes, which usually comes on in younger people and is associated with the failure of the pancreas to produce insulin, is caused by an over-responsive immune reaction, possibly to a viral infection. If researchers can show a causation effect between COVID-19 and diabetes, then this may help support that theory and help us understand the causes of Type 1 diabetes in general.
The truth is we are learning about the coronavirus and its effects on the body in real time. It looks possible that there is a link between the virus and diabetes; whether or not that is a direct link will take a number of years and studies to determine, but until then doctors will continue to monitor the blood sugar levels of those who are admitted to hospital with COVID-19.
