Up-to-date evidence! "Intestinal coxsackievirus infection" is an important cause of type 1 diabetes! Vaccines are already in development

Introduction: Type 1 diabetes is an endocrine metabolic disease caused by the destruction of pancreatic islet β cells and the inability to secrete insulin, resulting in disorders of sugar, fat and protein metabolism, which seriously endangers people's health, but the cause is unknown
.
The latest study has found that "intestinal coxsackievirus infection" may be an important factor in the onset of type 1 diabetes, and the "type 1 diabetes vaccine" for this mechanism has entered the clinical research stage
.

Coxsackie virus (Source: Visual China)

Type 1 diabetes is influenced by both genetics and environment

Type 1 diabetes mellitus (T1D) has an unknown etiology, which is an endocrine metabolic disease that causes disorders of sugar, fat and protein metabolism due to the destruction of pancreatic islet β cells and the inability to secrete insulin, which seriously endangers people's health
.

In the past 60 years, the incidence of T1D in the world has increased by 3%~5% per year, about 1 times
every 20 years.
The incidence of T1D in children is also increasing worldwide, with the fastest increasing rates of 10%
per year in the region.
Genetic factors influence the occurrence and progression of T1D, but less than 50% of T1D cases are due to genetics as an independent causative factor, suggesting that environmental factors also play an important role
in the development of T1D.
Numerous studies have shown that human enteroviruses, such as coxsackie group B virus infection, are strongly associated
with the development of T1D.

What is the Coxsackie virus?

Coxsackievirus (Coxsackievirus) is an enterovirus, divided into A and B categories, is a common type of viruses that infect the human body through the respiratory tract and digestive tract, can cause a variety of diseases, including acute and chronic myocardial diseases, respiratory diseases, hand-foot-mouth syndrome, conjunctivitis, meningitis, etc.
, after infection, people will have fever, sneezing, cough and other cold symptoms
.

Coxsackievirus was first obtained in stool samples by Dr.
Gillbert Dalldorf and his colleagues in 1948 in the search for a cure for polio disease, and is named
after its discovery in the small town of Coxsackie, New York.
Like other types of enteroviruses, coxsackievirus can be transmitted
through the "fecal-oral route" and "oral-oral route".

There have been reports
of pancreatic damage leading to diabetes mellitus caused by Xcoxsackie's virus infection.
Experiments have shown that coxsackievirus infection of β cells cultured in vitro can cause lysis, solidification and death
of β cells.
In the coxsackievirus CVB 4 type is most closely related to T1DM, other strains such as CVB 5 do not seem to induce diabetes in mice, but after repeated passage, the genotype can be changed, and infected mice can also cause diabetes-like syndrome (chronic pancreatitis, blood sugar imbalance, acinar tissue destruction and mild isletitis).

Episode 1 diabetes? Latest evidence points to "intestinal coxsackievirus infection"

The onset of type 1 diabetes is influenced by both genetic and environmental factors, and the latest research has found that "intestinal coxsackievirus infection" may be the "detonator" for the onset of type 1 diabetes!

Enteroviral infections and type 1 diabetes date back more than 50 years
.
A 1969 study raised concerns about the association between new-onset diabetes and coxsackie-B enterovirus infection; In 2011, foreign research groups published a retrospective study to attract people's attention to enterovirus infection and type 1 diabetes, and the latest academic results published at the annual meeting of the European Association for the Study of Diabetes in 2022 are an important cause
of type 1 diabetes.

The systematic analysis included data from 60 studies covering approximately 12,000 participants and found that:

➤ Within the first month of diagnosis of type 1 diabetes, patients are 16 times more likely to develop enterovirus infection than the general population;

This association was stronger in people with a genetic predisposition to type 1 diabetes or a first-degree relative of the disease (29 times more likely to have enterovirus infection).

➤ An in-depth analysis of virus types found that coxsackie B virus infection was most closely associated with type 1 diabetes
.

The researchers note that the number, timing, duration and even site of infection of enteroviral infections may also be important
.
The "leaky gut" hypothesis suggests that viruses originating in the gut can travel to the pancreas along with activated immune cells, and that low levels of persistent infection and resulting inflammation lead to an autoimmune response
.

But this does not mean that enterovirus infections are the only cause
of the onset of type 1 diabetes.
Viruses that cause diabetes seem to involve other factors such as diet, an imbalance in the gut microbiome, the uterus (during pregnancy) or chemical exposure in early
childhood.
But there is no doubt that these findings provide further support
for the development of vaccines to prevent the development of islet autoimmune diseases and reduce the incidence of T1D.
”

A "vaccine for type 1 diabetes" is under development

Type 1 diabetes is a highly heterogeneous disease, and if it is proven that an enteroviral infection plays a key role in certain populations, preventing such viral infections could significantly reduce the incidence
of new cases.

A team of researchers in Europe has developed a vaccine against coxsackie-B enterovirus, which is currently being tested in humans to reduce the risk of developing type 1 diabetes in high-risk
children.

Resources:

[1] Rich Haridy.
Increasing evidence a common virus triggers type 1 diabetes.
2022-10-2.
https://newatlas.
com/health-wellbeing/ enterovirus-evidence-common-virus-triggers-type-1-diabetes/

[2] K.
-P.
Knoch,A.
Kosok,Z.
Marinicova,et al.
Coxsackie virus protease 2A alters the sorting of insulin secretory granule cargoes and induces the premature activation of cathepsins.
https://link.
springer.
com/article/10.
1007/ s00125-022-05755-w

[3] https://clinicaltrials.
gov/ct2/show/NCT04690426

[4] CHEN Sisi, ZHENG Yu.
Research progress on the relationship between coxsackievirus and the pathogenesis of type 1 diabetes.
International Journal of Pediatrics.
2011,38(3): 310-312,Cover 3.

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[5] SUN Chunrong, CUI Xiaodai.
Research progress on the relationship between coxsackievirus and the pathogenesis of type 1 diabetes.
International Journal of Pediatrics.
2006,33(3): 159-161.

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