Infectious Disease

References to COVID-19 as a cause of emerging diabetes “contradicting”

March 20, 2021

4 min read

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Source:

Atkinson M et al. The endocrine system in the COVID pandemic. Presented at: ENDO annual conference; March 20-23, 2021 (virtual meeting).

Disclosure:
Atkinson does not report any relevant financial information. Rubino reports that he has received research grants, consulting and consulting fees from Ethicon, GI Dynamics, Keyron, Medtronic, the National Institute for Health Research, and Novo Nordisk.

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Case reports and news articles have reported on the possibility of some form of emerging diabetes related to COVID-19 infection. However, epidemiological data suggest that there is still much to be learned before final conclusions are drawn.

Mark Atkinson

“If these articles ask the question of whether COVID-19 can cause diabetes, these are studies [referenced] are case reports describing a form of diabetes that occurs within a reasonable time after a COVID-19 infection. ” Mark Atkinson, PhD, Jeffrey Keene University of Florida Family Professor and Director of the University of Florida Diabetes Institute said during a pre-meeting presentation at the ENDO annual meeting. “What is confusing about these cases is that sometimes they look like ‘classic’ Type 1 or Type 2 diabetes, but in other cases the presentations don’t exactly fit those two types. The question has become, is this a new form of diabetes? Is it really a loss of insulin or liver glucose production, or both? Then it was reported that COVID-19 infection causes hyperglycemia in many people. “

Diabetes Words 2019

Source: Adobe Stock

The epidemiological literature examining whether SARS-CoV-2 is associated with an increased incidence of diabetes is contradicting, Atkinson said. A multicenter regional study conducted in the UK and published in Diabetes Care in August showed researchers found an 80% increase in new type 1 diabetes cases during the pandemic compared to a typical pre-pandemic year estimated that apparent clusters were observed in two units.

However, a much larger study conducted in Germany, which was also published in Diabetes Care, showed that the incidence of type 1 diabetes in 2020 followed the increasing trend observed between 2011 and 2019 with no upward or downward deviation, indicating this that no short-term impact of the COVID-19 pandemic.

Francesco Rubino

“The message is that there is clearly a two-way relationship between diabetes and COVID-19, but it remains to be seen whether COVID-19 can actually cause new diabetes and we wanted to investigate that with a registry.” Francesco Rubino, MD, Professor and Chair of Metabolic and Bariatric Surgery at King’s College London and Honorary Advisor at King’s College Hospital, said Healio. “There is no question that there is an interplay between the two diseases. Whether COVID-19 triggers diabetes in predisposed people or causes new diabetes is currently being investigated. “

What Can Connect Diabetes, COVID-19

From the beginning, researchers have focused on the mechanism by which the virus enters cells – the angiotensin converting enzyme 2, or ACE2, which was established as the COVID-19 receptor.

Some research suggests that ACE2 can be expressed in beta cells and in the kidneys, which explains an increase in emerging cases of diabetes with rising COVID-19 infection rates, Atkinson said.

There, too, the data are contradictory, he said.

“An article in the New England Journal of Medicine said that SARS-CoV-2 could affect diabetes for this reason [ACE2] The receptor is expressed in beta cells and in the kidneys. The challenge here is that the most cited paper was published over 10 years ago in a low impact journal that was a case and lacked detail, ”Atkinson said. “This article on coronavirus and beta cell expression had very few citations, but it exploded last year. Hence, this notion of ACE2 expression in beta cells has almost become dogma, but it is controversial. “

Small studies examining the expression of ACE2 in induced pluripotent stem cells that have turned into beta-cell surrogates, as well as studies with isolated islet cells and pancreatic sections, have shown ACE2 expression, Atkinson said.

“You might think, at this point, that there is a certainty about it,” Atkinson said. “In reality, my own group published a study in Cell Metabolism in December in which we looked intensively at normal pancreases in all age groups and could not find the expression of ACE2 in beta cells. We could see it at the mRNA level, but it was limited to pancreatic ducts. ACE2 expression occurs in the pancreas, but not in the endocrine cells. “

Rubino said other options should be explored.

“Sometimes people focus on whether the virus can attach to the beta cell in the pancreas. The evidence there can be confusing, ”Rubino said in an interview. “Some studies show that; some not. However, if we only focus on the beta cells, our focus will be too narrow. We should look at other possibilities – defects in the pancreas as a whole, not just beta cells, and defects and damage in other organs that can lead to dysfunction in the endocrine cells, such as the intestines, liver, adipose tissue. We learn day by day that this virus can cause microthrombosis and damage organs. Inflammation can lead to systemic dysfunction. At the moment we are not clear about which biological pathways are relevant, but there is certainly a clinical interaction. “

Learn from case reports

With many factors still unknown, Rubino and a group of leading diabetes researchers have set up a global registry for COVID-19-related diabetes cases. The registry, a joint initiative with King’s College London and Monash University, aims to identify the extent and characteristics of emerging COVID-19 diabetes and examine its pathogenesis, management and outcomes. The registry also collects data on presentations with severe metabolic disorder in pre-existing diabetes, such as: B. diabetic ketoacidosis.

“We started this project on the hypothesis that there might be a link between COVID-19 and diabetes, and at the same time we announced the creation of a global registry where leading experts from around the world will collect as much information as possible. from as many clinicians as possible, ”said Rubino. “We believe that many of the emerging diabetes cases we find are actually pre-existing diabetes. Or maybe a minority will really emerge, but by asking the whole world to contribute, we hope to collect a large sample of cases to really understand the relationship between diabetes and COVID-19. “

In order to assess whether a diabetes case is really new diabetes, secondary hyperglycaemia due to an acute illness, or a pre-existing illness, the researchers, in collaboration with leading experts, use a number of criteria that are based on the HbA1c medical history Administration of drugs such as dexamethasone and other possible criteria include triggers for hyperglycemia.

“What is the development? Does the hyperglycemia resolve with the resolution of the COVID-19 peak or does it persist? “Said Rubino. “We hope to understand more.”

To submit a case to registration, clinicians must work with their facility to apply for and sign a data exchange agreement. To date, more than 400 people have requested data sharing and 30 clinicians have completed the process and exchanged information on more than 300 cases.

“We hope that this will increase exponentially in the coming weeks,” said Rubino. “We hope to be able to apply what we have learned to other viruses as well. We can learn more about diabetes in general. In addition to COVID-19, these people are vulnerable to another pandemic. This should be a call to all of us. “

Reference:

COVIDIAB registration. Available at: https://covidiab.e-dendrite.com. Accessed March 19, 2021.

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