A relationship between COVID-19 and diabetes was seen by doctors early in the pandemic. Not only were cases of COVID-19 more severe in patients with pre-existing diabetes but a number of subjects were seen to develop symptoms of diabetes during their acute SARS-CoV-2 infection.
Several studies subsequently pointed to higher rates of newly diagnosed diabetes cases in COVID-19 patients. The correlation was seen in both adults and children but researchers did not know if this novel coronavirus was directly causing a new kind of diabetes.
Was COVID-19 directly speeding up development of the disease in those already prone with prediabetes? Is the nature of the pandemic simply leading to doctors catching more cases of undiagnosed diabetes in the general population? And what are the long-term outcomes for these COVID-19 patients with newly diagnosed diabetes?
A new study led by Harvard Medical School researchers at Massachusetts General Hospital has attempted to tease out some answers to these questions. The researchers studied medical records from several hundred subjects presenting to hospital with COVID-19 in 2020.
Of those cases studied, the researchers homed in on 78 subjects who had no pre-existing diagnosis of diabetes, yet presented upon admission with diabetic symptoms. The first observation was that demographic data indicated these new COVID-related cases of diabetes were more likely to appear in young subjects with limited English proficiency and low levels of health insurance.
This led the researchers to hypothesize that COVID-19 was not necessarily a direct cause of diabetes. Instead it was possible hospitalization with the disease was allowing doctors to identify either prediabetic patients or undiagnosed diabetic patients, at higher rates than normal.
“This suggests the term 'newly diagnosed diabetes' may be more appropriate than 'new-onset diabetes,' as it is unclear in many cases whether the diabetes is truly new-onset or merely newly recognized,” the researchers wrote in the new study. “Additionally, given this finding, we believe it is possible that infection with COVID-19 may not directly cause diabetes, but instead may push patients with pre-diabetes into frank diabetes and push patients with undiagnosed diabetes into extremis, as suggested by some experts.”
Another observation in the new study supporting this hypothesis is the novel long-term follow up data on the COVID-19 patients experiencing newly diagnosed diabetes. Almost all the newly diagnosed COVID-related diabetic cases somewhat resolved within a year of hospital discharge, with only 7.8 percent of those new diabetes diagnoses requiring insulin at the 12-month follow-up.
"This suggests to us that newly diagnosed diabetes may be a transitory condition related to the acute stress of COVID-19 infection," said Sara Cromer, lead author on the new study. "Instead of directly causing diabetes, COVID-19 may push patients with pre-existing but undiagnosed diabetes to see a physician for the first time, where their blood sugar disorder can be clinically diagnosed. Our study showed these individuals had higher inflammatory markers and more frequently required admission to hospital ICUs than COVID-19 patients with pre-existing diabetes."
The temporary nature of diabetic symptoms in many COVID-19 patients strengthens the idea that the virus is not directly infecting and damaging insulin-producing beta cells. But it’s more probable, according to the researchers, these cases of new-onset diabetes are due to a condition called stress hyperglycemia.
Stress hyperglycemia is when an acute illness causes a temporary spike in blood glucose levels. For most people the condition recedes when the illness-related stress dissipates, but for a small amount of people it can lead to full-blown diabetes.
"Our results suggest that acute insulin resistance is the major mechanism underlying newly diagnosed diabetes in most patients with COVID-19, and that insulin deficiency, if it occurs at all, is generally not permanent," Cromer explained. "These patients may only need insulin or other medications for a short time, and it's therefore critical that physicians closely follow them to see if and when their conditions improve."
The study is certainly not the definitive answer to the COVID-diabetes mystery, but it does offer one of the first longitudinal investigations into those new diabetes cases that seem to appear alongside COVID-19. More work will be needed to validate these findings in other cohorts and better understand exactly how a SARS-CoV-2 infection is directly triggering acute hyperglycemia.
The new study was published in the Journal of Diabetes and its Complications.
Source: MGH