A recent report in Nature details the rationale and proposed mechanisms behind the ability of the virus to damage specialized cells in the pancreas that make insulin, otherwise known as beta cells, contained in surrounding specialized cells (islets).
When beta cells are destroyed, and the body is unable to manufacture insulin, a person develops elevated blood sugar, known as hyperglycemia, which effectively switches the body to an alternate pathway for energy using ketones and ketone bodies as a primary source. Using ketones bodies for energy will trigger a dangerous state where the body produces harmful acids, leading to diabetic ketoacidosis (DKA), which can be fatal if left untreated.
What’s clear is that diabetes is already recognized as a key risk factor for developing severe Covid-19, and persons with this condition have a higher risk of death.
But new research is emerging that the virus not only causes a more severe course in diabetics, but may also trigger onset of the condition in a subset of patients. The potential for a crush of patients with new onset diabetes (Type 1) may be a new reality that the medical community is yet to face.
“It’s important to note that not only are new diabetes cases possible but the more common scenario would be the development of diabetes complications in patients who already have diabetes such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia syndrome (HHS), said Dr. Minisha Sood, an endocrinologist at Lenox Hill Hospital in New York City. “These conditions are characterized by very high blood glucose and dehydration, among other symptoms.”
Clinicians are now seeing previously well people with no history of diabetes who have suddenly developed new onset diabetes after being infected with SARS-CoV-2, along with the dangerous complication, DKA, in which people develop acid in their blood stream, accompanied by rapid breathing, which can lead to shock and death.
“Knowing the symptoms of DKA and HHS is important so one may seek medical care in a timely manner. It’s critical for patients with diabetes to have a plan in place should they contract Covid-19 in terms of having enough medication, glucose testing supplies and access to their doctors and healthcare providers should they develop complications,” added Sood.
If we look back at patients who developed SARS back in 2002-2003, there is a linkage with development of autoimmune conditions such as type 1 diabetes. We also know that many organs which play a role in regulation of blood sugar—the liver, pancreas, kidneys, small intestine and adipose tissue (fat)— have a large number of ACE-2 receptors, the receptor on the surface of cells that the virus attaches to using its “spike protein”. Thats said, the basis for onset of ketosis-prone diabetes following infection with influenza or herpes has been previously reported in the medical literature.
Additional research recently published using miniature lab grown pancreases also suggests that the virus may cause diabetes by injuring the specialized cells, beta cells, that regulate blood sugar.
That said, other researchers have been less convinced about the strength of the connection between Covid-19 and new onset or worsening of diabetes.
“We need to keep an eye on diabetes rates in those with prior COVID-19, and determine if rates go up over and above expected levels,” said Naveed Sattar, a metabolic-disease researcher at the University of Glasgow, UK in the Nature report.
Clearly, more rigorous studies will be necessary to more definitively establish this link.
That said, a new collaborative research endeavor, the CovDiab Registry, was recently established by a group of researchers to study the presentation and spectrum of illness of patients with newly developed diabetes or complications related to existing diabetes.
The Registry will be useful, the researchers believe, in order to determine not only causes, but whether the diabetic state as a result of Covid-19 is permanent. Another goal will also be to look at those who are pre-diabetic and determine whether Covid-19 accelerates the pathway to Type 2 DM.
In fact, a letter published last month in the New England Journal of Medicine and signed by an international group of 17 leading diabetes experts involved in the CoviDiab Registry project, announced the establishment of the Global Registry of new cases of diabetes in patients with COVID-19.
Clinical observations thus far demonstrate a bi-directional relationship between Covid-19 and diabetes. On the one hand, diabetes is associated with increased risk of Covid-19 severity and mortality. Between 20 and 30% of patients who died with Covid-19 have been reported to have diabetes. At the same time, new-onset diabetes and life threatening metabolic complications of pre-existing diabetes such as DKA have also been in people with Covid-19.
“Diabetes is one of the most prevalent chronic diseases and we are now realizing the consequences of the inevitable clash between two pandemics,” said Francesco Rubino, Professor of Metabolic Surgery at King’s College London and co-lead investigator of the CoviDiab Registry project in a press release.” Given the short period of human contact with this new coronavirus, the exact mechanism by which the virus influences glucose metabolism is still unclear and we don’t know whether the acute manifestation of diabetes in these patients represent classic type 1, type 2 or possibly a new form of diabetes.”
One research group at Weill Cornell Medicine in New York City believes that the virus may directly damage the pancreas itself. Using so called “organoids”, miniature artificial lab- grown organs, Shuibing Chen and her team demonstrated that the virus can infect beta cells (which make insulin) a portion of which die. The virus seems to also induce production of cytokines which can trigger what’s believed to be an inflammatory response that can lead to death of beta cells.
We certainly don’t have all the answers just yet. While the organoid study does add some strength to the premise that SARS-CoV-2 may either cause or make existing diabetes worse, this research is still not enough to establish a definitive link, let alone causation.
It’s certainly possible that SARS-CoV-2 could produce a heightened inflammatory state which could inhibit the ability of the pancreas to accurately detect glucose and release insulin, while diminishing the capacity and ability of the liver to sense insulin. The end result could potentially lead to diabetes. That said, severe fatigue and muscle atrophy or breakdown could place people at risk for pre-diabetes into a diabetic state.
Long term studies will be essential to better understand the multiple potential mechanisms involved. Stay tuned!
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