5 May 2020

Weird link between diabetes and COVID-19

COVID-19 Diabetes

People with diabetes are more likely to get COVID-19, and become sicker when they do. And the infection may even trigger diabetes in people who don’t have it, leaving scientists to wonder why.

“Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections,” Monash University professor Paul Zimmet, and colleagues, said in a recent paper in The Lancet Diabetes & Endocrinology.

The international group of diabetes experts noted that when people with diabetes caught coronavirus, they were more likely to wind up with adult respiratory distress syndrome and multi-organ failure than their peers. In some parts of the world, 20 to 50% of patients struck down with COVID-19 have diabetes.

This isn’t unique to the latest coronavirus though. MERS and SARS also appear to have been worse for people with diabetes, with reports indicating the risk of death from SARS was up to 50% higher among those with diabetes compared with those without it.

These concerns are echoed by the authors of a recent MJA article, who highlighted a recent analysis showing that diabetes was a predictor of mortality from COVID-19.

“This association seemed to be driven by glycaemic control, with an independent association with elevated fasting plasma glucose,” Dr Emma Scott, of the Royal North Shore Hospital, and colleagues wrote. “This further highlights the need to maintain ongoing medical care to optimise glucose control throughout the current COVID-19 pandemic.”

So what’s behind this link?

In general, people with diabetes are more at risk of infection because the condition weakens their innate immune system.

But Professor Zimmet points to two mechanisms that might specifically increase the risk of COVID-19 infections.

“First, to gain entry to its target cells, the SARS-CoV-2 virus hijacks an endocrine pathway that plays a crucial role in blood pressure regulation, metabolism and inflammation,” he wrote.

Acute hyperglycaemia ramps up ACE2 enzyme expression on cells, which is the very receptor that the virus uses to gain entry to the cell.

“However, chronic hyperglycaemia is known to downregulate ACE2 expression making the cells vulnerable to the inflammatory and damaging effect of the virus,” he added.

The virus could also be using these enzymes to attack the pancreas and affect insulin production, triggering diabetes in people with no history of the condition.

While this hasn’t yet been confirmed, Italian researchers found severe diabetic ketoacidosis on admission to hospital, and other centres have found “tremendous” insulin requirements in patients who are severely ill with COVID-19.

Another explanation for the link between diabetes and COVID-19 is the dipeptidyl peptidase-4 (DPP-4) enzyme.

This enzyme is key in the body’s insulin and glucose response, and also increases inflammation in type 2 diabetes. The coronavirus responsible for MERS used this enzyme to infect cells.

But Associate Professor Sof Andrikopoulos, CEO of the Australia Diabetes Society, warned that the data wasn’t yet clear that diabetes made people more susceptible to COVID-19.

Type 2 diabetes was more common among older people and those with comorbidities such as cardiovascular disease, which might, instead, be to blame, he said.

The evidence was clear that having diabetes was linked to worse outcomes though, he said. This meant that people with diabetes should take extra care of their health.

Professor Andrikopoulos emphasised the importance of creating and revisiting sick day plans for patients with diabetes. He urged patients not to be afraid of seeing their doctor, either by telehealth or in person, if necessary, and not to delay their pathology tests.

Dr Zimmet said it was important to prevent diabetes in the first place.

“All patients without diabetes and particularly when at high risk for metabolic disease, who have contracted the viral infection need to be monitored for new onset diabetes that might be triggered by the virus,” he wrote.

Dr Scott recommended that doctors screen any patients presenting with COVID-19, or any illness, for SGLT2 use.

“With the increased use of SGLT2 inhibitors in Australia and internationally, all individuals treated with SGLT2 inhibitors should be educated of the need to withhold these drugs during illness to minimise the risk of ketoacidosis,” Dr Scott said.

Several webinars for GPs on the management of diabetes are currently running on the Australian Diabetes Society website.

MJA 2020, 24 April

The Lancet Diabetes & Endocrinology 2020, 23 April

COVID-19 live update