Medical researchers from around the world have started shining the spotlight on a new issue: that Covid-19 may not just be a risk for people with diabetes, it may actually cause diabetes.

Diabetes has been in the spotlight ever since the first reports of COVID-19 started surfacing from Wuhan, China. From December 2019, until now, growing data have revealed that people with diabetes are at higher risk of infection, hospitalisation, intensive care admission and of death. As scientists chip away at data and details, it has become clear that the COVID-diabetes connection is more complex than imagined.

The Covidiab Registry
Sporadic reports on how coronavirus also triggers diabetes in people with no history of diabetes, both type 1 and type 2, in both children and adults, have appeared since early 2020. In June, an International group of leading diabetes researchers set up a global Covidiab Registry (http://covidiab.e-dendrite.com), to establish the history, extent and outcomes of Covid-19 patients with abnormal blood sugar levels who have no prior history of diabetes. Doctors around the world are tracking information and uploading anonymous data of patients.

Emerging evidence suggests that a bidirectional relationship exists between COVID-19 and diabetes: you can get the worst case of Covid-19 if you are diabetic (or pre-diabetic) and you can get the worst case of diabetes if you have Covid-19. Unanswered questions abound: what type of diabetes does Covid-19 trigger? Is the new-onset diabetes an unknown side effect? Is it temporary? Does it disappear eventually in patients who recover? What are its effects after the complications of the virus and diabetes subside? Or does Covid-19 cause diabetes for life?

Invading The Gut
Scientists are fitting together puzzle pieces, joining the dots and making all possible connections. What is understood to date is that the SARS-CoV-2 virus that causes COVID-19) uses the angiotensin-converting enzyme 2 (ACE2)—found on the outer surface of cells in human lungs, arteries, heart, kidney, intestines and many other organs—as a cellular doorway to invade and infect a wide range of cells.

ACE2, which is a key regulator of blood pressure, wound healing and inflammation, is critical to our immunity. Some evidence suggests that ACE2 may be higher in patients with hypertension, diabetes and coronary heart disease. ACE2 is also widely present in key metabolic organs, including the pancreatic beta cells, which synthesise, store and secrete the hormone insulin—crucial for converting blood sugar into energy. This can help explain why glucose metabolism can be altered by the virus.

Moreover, there is emerging evidence of cross-talk between the gut hormones, the pancreas and the brain, a process involved in controlling blood sugar. If the coronavirus interferes with these signals, that could provide a biological basis for how Covid-19 comes to be associated with diabetes. That’s why. gastrointestinal symptoms are believed to plague one out of 10 Covid-19 sufferers. And doctors in China have discovered copies of coronavirus in the faeces of Covid-19 patients.

The Unusual Diabetes
Doctors around the world are uploading case studies of unusual diabetes in the Covidiab Registry. There are cases of Covid-19 patients who show symptoms that don’t fit the typical manifestations of diabetes: type 1 and type 2. In type 1 diabetes, immune cells destroy the cells in the pancreas that produce insulin. In type 2, the body gradually becomes resistant to insulin.

Doctors are witnessing mixed type of diabetes in Covid-19 patients, with previously unknown manifestations: sometimes called hybrid diabetes, sometimes double diabetes, with symptoms of both type 1 and type 2. Whatever damage the virus causes to a patient’s insulin-making cells, doctors are seeing blended features of both types showing up spontaneously in people recently diagnosed with Covid-19. And the treatment regimen swings from insulin injections (for type 1) to oral anti-diabetic drugs (for type 2).

The Clinical Puzzles

According to a case report, diabetic ketoacidosis was triggered in a previously healthy patient a week after presenting with symptoms of Covid-19. Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes due to insulin deficiency, when blood sugar rises to very high levels, with dangerous accumulation of toxic substances (ketone bodies) turn the blood acidic, sometimes with fatal consequences. The treating physician resolved the ketoacidosis and started the patient on insulin therapy, as in type 1 diabetes management. Did the virus disrupt the pancreatic beta–cell functioning?

In another study of 658 Covid-positive patients, about 42 were hospitalised with elevated blood concentrations of ketone bodies. About 27 previously non-diabetic patients had developed ketosis (occurs when low insulin levels cause the body to burn fat, producing ketones in the blood). Out of them, two developed severe ketoacidosis. Fifteen patients, with previously detected diabetes, had also developed ketoacidosis.

It is suggested that once in the islet cells of the pancreas, the SARS-Cov-2 virus disrupts normal cell function leading to abnormalities in insulin secretion and blood glucose maintenance. It is also possible that the virus invasion leads to acute inflammation that kills the islet cells. Either way, Covid-19 might accelerate the breakdown of fat, inducing ketosis (or ketoacidosis) in patients without diabetes, and ketoacidosis in patients with diabetes.

People with diabetics at Risk

What explains the increased risk of diabetes in Covid-19 patients?
Medical researchers are taking a re-look at the linkages between diabetes and infections. It is well-known that high blood sugar weakens the immune system and makes it less able to fight off infections. There are recorded cases of acute diabetes developing after mumps, hepatitis viruses, influenza virus, enterovirus infections and more. During the SARS outbreak of 2002-04, caused by another coronavirus, cases of acute onset diabetes were reported. The diabetes resolved after a few years for some, but persisted for others.

Not just infections, obesity (especially, abdominal obesity) is also a risk factor for severe infection. And many patients with type 2 diabetes are obese. It was illustrated during the influenza A H1N1 epidemic in 2009 that the disease was more severe and had a longer duration in about twofold more patients with obesity, who were then treated in intensive care units compared with background population. Obese patients also have an increased risk of asthma, considered a significant risk factor for developing severe Covid-19, hospitalisation and intubation. What’s more, diabetic complications such as kidney disease and ischaemic heart disease may further increase the severity of Covid- 19 in people with diabetes.

Heed a few precautions

Meanwhile, scientists are uploading case-studies on the Covidiab Registry. What is increasingly beyond dispute is that Covid-19-related diabetes is not just an anecdotal problem. It might be a while, though, before there is enough research to answer questions about prevalence, mechanism, what might predispose people to this particular coronavirus complication and who might be at risk.

Until then, people with diabetes will need to be careful more than ever before. Doctors suggest a few precautions: if you do not have diabetes and have been diagnosed with Covid-19, notice if you are passing urine more often than usual. If you have recovered recently from symptoms like fever, coughing, and loss of smell, and still feeling fatigued, ask your doctor about getting a blood sugar test done.