When Ziyad Al-Aly’s research team told him how often diabetes seemed to hit COVID-19 survivors, he thought the data must be wrong and asked his five colleagues to recreate the numbers.
Weeks later, they returned the same results after going through millions of patient records. By this point, Al-Aly had also looked into the scientific literature and was beginning to grapple with an alarming reality: COVID-19 is not only more deadly to people with diabetes, it also triggers metabolic disease in many who did not before have it.
“It took me a while to convince,” said Al-Aly, who heads the clinical epidemiology center for the Veterans Affairs St. Louis Health System in Missouri. “It was hard to believe that COVID could do this.”
Among the many ripple effects of COVID-19, the worsening global diabetes burden could place a heavy burden on public health. The underlying mechanisms that trigger emerging diabetes are not clear, although some doctors suggest that the SARS-CoV-2 virus can damage the pancreas, the gland that produces insulin, which is needed to convert blood sugar into energy . Sedentary lifestyles induced by lockdown could also play a role, as could late diagnoses after people avoided doctor’s offices. Even with some mild coronavirus cases in children, diabetes can develop quickly, according to scientists.
Considered a lung disease in the early days of the pandemic, COVID-19 is increasingly recognized for its ability to devastate multiple organs and body systems, causing persistent and sometimes debilitating symptoms for 1 in 10 people months after their apparent recovery.
Persistent metabolic complications, sometimes requiring high doses of insulin, suggest a subset of survivors will develop diabetes – adding to the number of the more than 463 million people with chronic disease.
The disease, in which the body does not make enough or use insulin properly, was estimated to cost an estimated $ 760 billion in the year prior to the onset of COVID-19, due to life-shortening complications ranging from stroke and kidney failure to foot ulcers and blindness included.
Al-Aly and colleagues were the first to measure the effects in the United States using data from the Department of Veterans Affairs’ national health databases. They found that in the six months after infection, COVID-19 survivors were 39% more likely to have a new diagnosis of diabetes than uninfected VA healthcare users. The risk is about 6.5 additional cases of diabetes for every 1,000 COVID-19 patients who do not end up in the hospital. For those who do, the odds go up to 37 per 1,000 – and even higher for those in need of intensive care.
Al-Aly said the numbers should be viewed in the context of the scope of COVID-19. During the winter summit, more than 130,000 patients with the coronavirus were hospitalized in the United States alone. Globally, SARS-CoV-2 is said to have infected more than 153 million people, including over 20 million in India, the country with the largest number of people suffering from diabetes after China.
Al-Aly’s data was published in Nature last month, three weeks after a study of nearly 50,000 COVID-19 patients hospitalized in England found that they were 50% more likely to develop diabetes about 20 weeks after discharge than the corresponding controls.
“We are at risk of two pandemics colliding,” said Francesco Rubino, Chair of Metabolic and Bariatric Surgery at King’s College London, who worked with Paul Zimmet, professor, to create a global registry of COVID-19-related diabetes cases at the Diabetes Center Monash University in Melbourne.
Researchers have hypothesized that COVID-19 could increase the likelihood of a diagnosis of diabetes, including the possibility that the pancreas’ insulin-secreting beta cells are destroyed either by the virus or by the body’s response to the infection.
Other explanations could include an acute stressful reaction to the infection, the use of steroid treatments that aid survival but increase blood sugar, or just unmasking cases of diabetes that had previously escaped diagnosis, according to John Nicholls, clinical professor of pathology at the University of Hong Kong.
Nearly 500 doctors from around the world have agreed to share data on Rubino’s diabetes registry. They upload known risk factors, laboratory results, clinical characteristics, treatment, and disease progression – information that can help determine the most common form of the disease, possible causes, and likely prognoses.
So far, almost 350 cases have been documented via the registry, and descriptive anecdotes flow through emails from affected patients and parents almost daily.
“People write to us and say, ‘My son has just been diagnosed with diabetes. He is 8 years old. He just got COVID a month or two ago. Could it be related? ‘”Said Rubino.
The question of whether SARS-CoV-2 can trigger diabetes is controversial. Monitoring diabetes using population-based data could be a clearer way to gauge the impact of the pandemic, said Jonathan Shaw, associate director of the Baker Heart and Diabetes Institute in Melbourne.
In Los Angeles, doctors are now reporting a worrying pattern in children with new cases of type 2 diabetes – the chronic form associated with obesity and sedentary lifestyle, which occurs primarily in adults.
They found that one in five new pediatric type 2 cases in the past year required hospitalization for diabetic ketoacidosis, a dangerous build-up of acid in the blood due to insufficient insulin supply. In contrast, only 3% of new patients faced this life-threatening problem in 2019. While none of the children had active COVID-19 in 2020, doctors did not systematically test for previous SARS-CoV-2 infection. A third of the test subjects were positive.
“Could that explain part of the climb? We really just don’t know, ”said Lily Chao, interim director of medical diabetes at Los Angeles Children’s Hospital. “But that’s one thing that goes through the back of our minds.”
Doctors in Canada suggest that a decline in medical use during the pandemic may have delayed care for children with emerging type 1 diabetes – the rarer form caused by an autoimmune reaction that destroys insulin-producing cells in the pancreas . A study from the province of Alberta found that the incidence of severe diabetic ketoacidosis more than doubled in these patients to 27% in 2020.
Chao sees other plausible drivers related to COVID-19. The pandemic itself has also resulted in lifestyle changes that can put children at risk for diabetes.
“Schools in Los Angeles were closed for a full year,” she said. “Many of our children have just been home and frankly have not got the best diet and gained more weight. It’s a complex situation. “
Rubino plans to release initial results from the diabetes registry data by mid-year and is already offering a word of early caution: there is ample evidence of the long-term consequences of COVID-19 that should be avoided at any age.
“This is not just flu, OK, you have it and you are done with it,” he said. “You may not be finished yet. It is a serious matter. “
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