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The causes of type 1 diabetes

Author: Dr Sorin Ioacara, MD, PhD
A woman with arms raised suggesting the question why?

Discover here: Causes during pregnancy | Causes after birth | Acceleration factors

Environmental factors play a significantly higher role among the causes of type 1 diabetes compared to genetic factors. This is also the reason why the incidence of type 1 diabetes has increased, primarily based on cases at low genetic risk. In other words, more and more people with low genetic risk end up with type 1 diabetes.

Environmental factors are initially involved in the development of type 1 diabetes-specific autoimmunity. They can act either in the intrauterine period or after birth. Some of them may also be risk factors, while others work as protective factors.

Causes of type 1 diabetes during pregnancy

A pregnant woman with a big belly, dressed in a red robe holds her belly with a hand.

During pregnancy, a lot of environmental factors act. They may increase or decrease the risk of type 1 diabetes in the future child. Ecological factors change the risk for type 1 diabetes specific autoimmunity. Most of them are related to the diet of the pregnant mother. The main risk factors for the development of autoimmunity specific to type 1 diabetes in children (after birth), which act during pregnancy are the following:

  1. Enterovirus infection
  2. Maternal obesity before becoming pregnant (pre-conception)
  3. Pre-conception father’s obesity
  4. Maternal obesity during pregnancy
  5. A higher baby weight at birth
  6. Cesarean birth
  7. The amount of gluten in the mother’s diet
  8. The mother’s older age

However, during pregnancy, there are also protective factors for the appearance of autoimmunity, among which the most important would be:

  1. Higher vitamin D levels in the mother
  2. Mild respiratory infections of the mother

Weight in utero

Pre-conception maternal obesity increases the risk of developing type 1 diabetes-specific autoimmunity by about 40%. This risk increases further with the persistence of excess weight during pregnancy.

Surprisingly, it appears that the father’s obesity at the time of conception increases the risk of autoimmunity by 50%. Excess baby weight in utero is a risk factor for autoimmunity if birth weight is higher than 3.5 kg.

Gluten-rich diet in pregnancy

A higher amount of gluten in the mother’s diet may be responsible for a significantly increased risk of developing autoimmunity specific to type 1 diabetes in the child. The risk is double for an intake of 20g of gluten per day compared to 7g per day. Among the gluten-rich foods we mention here:

  • bread
  • pasta
  • pastry
  • bagels
  • biscuits

Vitamin D in pregnancy

A diet rich in vitamin D during pregnancy is associated with a higher level of vitamin D in pregnant women. This higher level of vitamin D obtained through diet reduces by half the risk of developing autoimmunity specific for type 1 diabetes in the future child.

Trying to increase the level of vitamin D in the mother using vitamin D supplements to reduce the risk of type 1 diabetes, unfortunately, does not work. Studies have shown that although there was a significant increase in vitamin D levels in the mother, the subsequent risk of type 1 diabetes in the child did not change.

Respiratory infections in pregnancy

Respiratory infections of viral origin during pregnancy do not increase the risk of developing autoimmunity specific for type 1 diabetes. On the contrary, in the presence of unique genetic variants, this risk may even decrease. In reality, these infections double the risk of developing type 1 diabetes, but the appearance of autoimmunity less often precedes it.

Stimulating the immune system naturally, by contacting some infections by the mother, can prevent the development of autoimmune diseases in children. In addition to the formation of antibodies, viruses induce essential changes in the immune system.

Viruses release some particular molecules in the body, called cytokines. Their effects are multiple and not completely known in terms of preventing the occurrence of autoimmunity specific to type 1 diabetes.

Another hypothesis described is “antigenic competition”. The immune system is trying to fight the virus. The response of the immune system to other antigens, such as those in the pancreas, is thus diminished. In other words, the immune system is “busy” eradicating the virus and forgetting about pancreatic beta cells.

However, congenital rubella or cytomegalovirus infection leads to diseases that include several organs and systems of the newborn and infant. Diabetes is present in about 10% of these cases.

Environmental factors involved after birth in the emergence of autoimmunity

An infant with a toy in his mouth.

After birth, there is an extremely important period for shaping the immune system. The baby has to adapt to new environmental conditions, including the presence of pathogens. During this period, the immune system learns to better distinguish the body’s own structures from foreign ones, which can harm it (pathogens). The main risk factors for the onset of autoimmunity specific to type 1 diabetes that act after birth are:

  1. Enterovirus infection
  2. Rotavirus infection
  3. Other viral infections
  4. Respiratory infections
  5. A higher rate of weight gain in the infant
  6. Premature exposure to cereals and root vegetables
  7. Cow’s milk
  8. Major mental stress

The protective factors for the appearance of autoimmunity that act after birth are the following:

  1. Breastfeeding
  2. Early exposure to gluten or egg
  3. Omega 3 fatty acids
  4. Probiotics
  5. The rotavirus vaccine

Enterovirus infection

Enterovirus infection in children can increase the risk of later-onset autoimmunity specific to type 1 diabetes by more than ten times. Enteroviruses are transmitted by the faecal-oral route. They can even colonize the digestive tract asymptomatically. The large group of enteroviruses includes:

  • poliovirus
  • coxsackieviruses
  • echovirus
  • other enteroviruses

The poliovirus can be considered eradicated and is not discussed here. Among coxsackieviruses, variant B1 is associated with a significantly increased risk for type 1 diabetes-specific autoimmunity. Infection with other coxsackievirus subtypes (e.g. B3 or B6) does not increase the risk of subsequent autoimmunity.

The reduction in this way of the risk of subsequent B1 infection decreases the risk of type 1 diabetes-specific autoimmunity.

Rotavirus infection

Rotavirus is an orally transmitted virus that infects cells inside the small intestine. It can cause diarrhoea in infants and young children. By the age of 5, almost any child has already been infected with this virus at least once.

It seems that infection with this virus can trigger the autoimmune process in the pancreas. Recent studies have shown that rotavirus vaccination is associated with a significant reduction in the risk of developing type 1 diabetes-specific autoimmunity.

Other viral infections

In addition to enterovirus and rotavirus, there are other types of viruses involved in the development of autoimmunity specific to type 1 diabetes. Their contribution is still incompletely elucidated. Of these viruses, some more consistent evidence exists for:

  • herpes viruses, including cytomegalovirus and Epstein-Barr virus
  • rubivirus (rubella)
  • rubulavirus (mumps)
  • parechovirus
  • picobirnavirus
  • tobamovirus
  • bacteriophage viruses

Bacteriophage viruses represent most of the viruses normally present in the intestine. Their role is to infect and destroy bacteria. They thus contribute to the regulation of the composition of the intestinal bacterial flora.

There are species of bacteriophage viruses that significantly increase the risk of autoimmunity in type 1 diabetes. At the same time, there are species of bacteriophages that decrease this risk.

The rubella virus has an interhuman transmission through the air. It produces an eruptive disease in young children and adolescents. Infection during pregnancy can lead to congenital rubella syndrome.

About 10-20% of children born with this syndrome also have an atypical form of diabetes. The rubella vaccine is included in the national compulsory vaccination program.

The protection offered by this vaccine is effective for the rest of your life. Therefore, the introduction of rubella vaccines into practice currently excludes this virus from the list of risk factors for type 1 diabetes.

Mumps virus causes epidemic mumps. The infection is common in children, where it evolves with an inflammation of the salivary glands. The parotids are most commonly affected. There is also sore throat or earache, fever, headache and lack of appetite.

Most of the time, mumps does not pose special problems. Immunization by widespread vaccination of children with attenuated mumps virus, currently excludes this candidate from the list of risk factors for type 1 diabetes.

Respiratory infections

Respiratory infections significantly increase the risk of developing autoimmunity specific for type 1 diabetes. Their onset in the first month of life doubles this risk. Infections can increase the risk of autoimmunity through the following possible mechanisms:

  • antibiotics used to treat them alter the intestinal flora. This has negative effects on the immune system, especially in infants.
  • activation of the interferon pathway in the immune response leads to local inflammation of pancreatic beta cells. This mechanism activates some special lymphocytes (CD8 +), which can destroy the pancreatic beta cells.
  • •the immune system has a genetically coded defect, which makes it respond aberrantly to a certain type of infection. The aberrant response is to confuse pancreatic beta cells with a real infection.

Weight in infants

Excess weight during infancy may double the risk of later-onset autoimmunity specific to type 1 diabetes. In addition, rapid weight gain carries an additional risk for autoimmunity.

The mechanism by which overweight leads to autoimmunity appears to involve increased resistance to insulin.

Cow’s milk

Cow’s milk may be responsible for the increased risk of autoimmunity specific to type 1 diabetes in children. However, this only happens in children with a low genetic risk for type 1 diabetes. In the presence of a high genetic risk for type 1 diabetes, exposure to cow’s milk does not change the risk of developing autoimmunity.

However, the use of a hydrolyzed formula, in which the cow’s milk-specific protein has been removed, does not alter the risk of type 1 diabetes compared to “whole” cow’s milk.

Regardless of the genetic risk, exposure to cow’s milk in the first three months of life may increase the risk of developing autoimmunity in the event of an enterovirus infection. This increase in the risk of autoimmunity is in addition to the increase brought about by the enterovirus infection itself.

Breastfeeding and gluten exposure

Breastfeeding is associated with multiple benefits for the infant. They are present both in the short and long term. One of the long-term benefits is the reduction by about 25% of the risk of developing autoimmunity specific to type 1 diabetes.

Celiac disease is an autoimmune condition commonly associated with type 1 diabetes. Responsible for the onset of autoimmunity in celiac disease is gliadin, a protein in gluten. Consequently, doctors suspected gluten exposure to be involved in type 1 diabetes development.

Studies that have tried to delay the baby’s gluten exposure until after the age of 9 months have not been able to show any benefit from this intervention. Attempting to delay gluten exposure beyond 12 months showed the same result. There was no influence on the risk of developing autoimmunity specific to type 1 diabetes.

Studies that have looked at whether premature gluten exposure before the age of 4 months influences the risk of developing type 1 diabetes have had a surprising result. This early exposure to gluten has reduced the risk of developing autoimmunity in type 1 diabetes by 30%.

Exposure to eggs

Studies have shown that the introduction of eggs in the infant’s diet before the age of 9 months is associated with a reduction in the risk of subsequent onset of autoimmunity specific to type 1 diabetes. The decrease in risk is about 20%. Except for gluten exposure before the age of 4 months, no other dietary option in infants significantly influences the risk of autoimmunity.

Some smaller studies have suggested a significantly increased risk associated with exposure to root legumes or fruits before the age of 4 months. An ample confirmatory research has shown that this is not true.

However, some populations may have particular risk factors for type 1 diabetes. Therefore, their risk factors might not be among those found in other communities in different geographical areas.

Environmental factors accelerating the progression of autoimmunity

Many arrows flying.

Stage 1 of type 1 diabetes diagnosis means that you have persistent autoimmunity against pancreatic beta cells. What follows is a period in which the progressive destruction of pancreatic beta cells takes place. This period can last for several months, several years or even several decades.

Environmental factors may accelerate the transition from autoimmunity to full-blown disease. This symptomatic onset of high blood sugar is the stage 3 in the development of type 1 diabetes.

The main environmental factors that can accelerate the transition to stage 3 of type 1 diabetes are:

  1. Enterovirus infection
  2. Insulin resistance (e.g. puberty, overweight)
  3. Hyperglycemic diet
  4. Changes in the intestinal bacterial flora
  5. Major psychological stress

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