Researchers have been searching for decades for the cause(s) of type 1 diabetes, and some recent evidence might point to an enterovirus. If this research holds up over time, we might be able to develop a vaccine for the enterovirus that could prevent type 1 diabetes.
This is very interesting data that might unlock one of the great puzzles of type 1 diabetes. The etiology of type 1 diabetes has eluded researchers for years, and this new data, which links it to an enterovirus, is game-changing.
This article will tell you all about diabetes and the new research.
What is diabetes?
Type 1 diabetes is an autoimmune disease that is characterized by autoreactive T lymphocytes (T-cells) that destroy pancreatic islet beta cells, which produce insulin. Essentially, these lymphocytes mistakenly attack the islet cells as if they were a foreign body, as they are supposed to do with a viral or bacterial infection.
In addition, regulatory T-cells (which are often called Tregs) modulate the immune system and would normally reduce the effect of an autoimmune attack. Tregs act like brakes that normally prevent mistaken attacks, like on the pancreatic islet cells, without affecting the whole immune system. A branch of diabetes research has suggested that abnormal Tregs could be the key to finding treatments to reverse type 1 diabetes.
Once the pancreatic islet cells are damaged, the body can no longer produce insulin, which is critical to regulating the levels of blood glucose. Without insulin, the blood glucose levels increase rapidly leading to long-term damage to eyesight, kidneys, limbs, heart, and other organs.
In fact, type 1 diabetes can be deadly if uncontrolled blood sugar leads to a life-threatening condition called diabetic ketoacidosis. Without regular insulin injections, a patient has little chance of living beyond a short period of time, and even then it could lead to a horrifically painful demise.
It is not known what causes this autoimmune disease, although there is strong evidence that genetics is the most important factor. However, there has been speculation that a trigger is necessary, possibly an infection. Just to be clear, vaccines are not linked to type 1 diabetes.
Currently, there are no known cures for type 1 diabetes. The only treatment for the disease is regular injections of human insulin, manufactured from genetically engineered E. coli cultures. In addition, careful diet and lifestyle management help regulate blood glucose levels, although they cannot replace insulin injections.
A little bit about enteroviruses
Enteroviruses are a genus of several RNA viruses that are associated with numerous diseases that afflict humans and other mammals. As of today, researchers have identified 84 different serotypes of human enteroviruses, although there is some variability in antigens within each of the different serotypes.
Early in the research on these viruses, they were given separate names, such as polioviruses, Coxsackie A viruses, Coxsackie B viruses, and echoviruses. Today, the viruses, as they are identified, are given names in a system of consecutive numbers. Enterovirus 68 (known as EV68, EV-D68, or HEV68) is the 68th on the list of these viruses.
Although many people claim that enteroviruses are only transmitted from the stool of an infected person (hence the “entero” portion of the name of the virus), they also can be found in respiratory secretions.
Probably, the most famous enterovirus is the poliovirus which is responsible for poliomyelitis. Poliovirus is an enterovirus, but not all enteroviruses cause polio.
There are 81 non-polio and 3 polio enteroviruses that can cause disease in humans. Of the 81 non-polio types, there are 22 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, and 25 other enteroviruses. Several of these viruses, such as poliovirus, are transmitted through the oral-fecal route, but others can be transmitted through oral-oral routes like simple sneezing.
According to the CDC, there have been many non-polio enterovirus outbreaks across the world recently:
- Coxsackievirus A16 is the most common cause of hand, foot, and mouth disease (HFMD) in the United States.
- Coxsackievirus A6 was the most commonly reported type of enterovirus in this country from 2009 to 2013, mostly due to a large outbreak in 2012 of severe hand, foot, and mouth disease. Some of the infected people developed symptoms that were more severe than usual.
- Coxsackievirus A24 and enterovirus 70 have been associated with outbreaks of conjunctivitis.
- Echoviruses 13, 18, and 30 have caused outbreaks of viral meningitis in the United States.
- Enterovirus 71 has caused large outbreaks of HFMD worldwide, especially in children in Asia. Some infections from this virus have been associated with severe neurologic diseases, such as brainstem encephalitis.
- Enterovirus D68 outbreaks have been documented in 2014, 2016, and 2018, causing respiratory illness in the United States
So, enteroviruses are quite common and have been associated with numerous outbreaks across the world.
Enterovirus and type 1 diabetes research
In a presentation at the European Association for the Study of Diabetes (EASD) meeting on 30 September 2022, Sonia Isaacs, Ph.D. candidate at the University of New South Wales, reviewed 48 studies on the topic of an enterovirus link to type 1 diabetes.
The researchers found the following:
- People with type 1 diabetes were nearly eight times more likely to have an enterovirus infection than those with normal pancreatic function, with an odds ratio (OR) = 7.99.
- Individuals with islet autoimmunity were two times more likely to have had an enterovirus infection, OR = 2.07.
- A subgroup analysis of individuals who were diagnosed with an enterovirus infection within the past 30 days was found to have to 16 times higher risk of recent-onset type 1 diabetes, OR=16.22.
- Individuals who carry one of the high-risk HLA genes and familial risk of type 1 diabetes had 141.1-times higher odds of prior enterovirus infection.
- A previous enterovirus A infection was linked to a nearly 4X greater risk of type 1 diabetes, with an OR = 3.7.
- A previous enterovirus B infection, OR = 12.7.
- A previous enterovirus C infection, OR = 13.8.
Enteroviruses A, B, and C include most of the Coxsackieviruses, and they are some of the most common enteroviruses that infect humans.
This is fascinating data that supports the hypothesis that some sort of infection, in this case, an enterovirus, might be the trigger for type 1 diabetes.
This research was presented at a meeting, so the data has not been peer-reviewed and published in a medical journal. However, this same research group has published previous systematic reviews and meta-analyses on enteroviruses and type 1 diabetes. I feel confident that I’ll be reading the peer-reviewed article soon enough.
But what do we do with this information? At the top of the list would be a vaccine that could prevent the enterovirus infections most closely linked to diabetes. If the vaccine worked, we could slash the risk of type 1 diabetes by huge amounts.
I’m going to give this study 5 out of 5 stars. It is a systematic review and meta-analysis which, as I’ve said numerous times, is at the top of the hierarchy of medical research. It provides clear data that shows a correlation between enteroviruses and type 1 diabetes.
However, I need to deduct a star because it hasn’t been published in a peer-reviewed journal as of this time.
So, the final number is 4 out of 5 stars.
- Yeung WC, Rawlinson WD, Craig ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ. 2011 Feb 3;342:d35. doi: 10.1136/bmj.d35. PMID: 21292721; PMCID: PMC3033438.