Type 1 Diabetes and Genetics: Who Is Predisposed?

Genetics plays a strong role in the development of type 1 diabetes. As an increasingly common chronic condition throughout the UK, the risk of developing diabetes tends to increase with certain genetic factors. For many that ask what causes type 1 diabetes, genetics doesn’t entirely determine who gets type 1 diabetes. Still, many studies have determined that it’s a strong component due to how type 1 diabetes affects the immune system, how it develops with other environmental factors and other reasons. Today, we’ll be exploring the relationship between genetics and diabetes type 1, is type 1 diabetes hereditary, and who’s the most predisposed towards getting this condition.


What Causes Type 1 Diabetes?

Unlike type 2 diabetes, which is usually caused by factors such as weight, age, and inactivity, the causes for type 1 diabetes are more obscure. While there is much greater awareness for type 2 diabetes, type 1 diabetes is not caused by a poor diet or an unhealthy lifestyle. It is an autoimmune condition where the immune system attacks itself and destroys the insulin-producing beta cells in the body. Because of this, there is no clear cause to what causes type 1 diabetes, but according to studies, certain genes put people at a greater risk for developing type 1 diabetes alongside other factors.


Before we dive into the genetic factors that play into diabetes type 1, researchers have also looked into other environmental factors that play a role in gene expression and other possible risk factors, including:


Viruses: Several researchers have put forth several viruses as a potential trigger for type 1 diabetes, with Human Enteroviruses having the strongest body of evidence. HEVs are a family of viruses that affect the digestive system, often appearing as a flu-like infection that the immune system fights off on its own. Some studies have found that traces of HEVs within the pancreas for both those newly diagnosed and those currently with diabetes type 1. The immune system may ultimately attack these cells mistakenly because of the similarities between the viruses and insulin cells.


Gut Microbiome: Alongside virus infections, the microbiome of individuals with type 1 diabetes has different strains of bacteria than those without type 1 diabetes. This link between the gut microbiome and this condition could be ultimately causing an impact on the immune system, impacting the body’s homeostasis and leading to type 1 diabetes.


Other factors: Hygiene, diet, pollutants, vaccines, ageing, and even psychological stress have all been put forth as environmental factors that could play a role in the development of type 1 diabetes. However, due to the inconclusiveness of these links and the lack of causality for type 1 diabetes, researchers continue to investigate type 1 diabetes through projects such as TEDDY and Diabetes UK.

The genetic factors behind this condition are complex because to determine how genetics plays a role in predisposing diabetes type 1, we need to understand the number of genes involved. The study of genetics isn’t simple, but we’re here to dive into the specifics of these genes to point out further why they’re connected.


The Connection Between Diabetes and Genetics

Diabetes and genetics have been a place of ongoing research, going as far back as the 1990s. Through study methods that include candidate gene association studies and genome-wide linkage analysis studies, these approaches have helped researchers gain knowledge about these specific genes. To try and narrow down the list; the genes most commonly looked at through research are defined by two categories:


HLA Genes: The HLA genes, also known as the HLA complex, are a family of genes that help the immune system distinguish the body’s proteins from proteins made by invaders such as viruses and bacteria. Certain members of the HLA complex are inherited by all individuals, while some gene expressions have more unique expressions identified by certain individuals. Within this complex, three general groups exist; HLA-A, HLA-B, and HLA-DR. These three groups have specific proteins with their own designations, designed to help the body distinguish between different proteins.

Non-HLA Genes: Other genes not within the HLA complex have also been identified by certain studies. This includes gene expressions such as the IDDM2, known as the insulin gene responsible for creating insulin-secreting beta cells, and CTLA4, a protein found on T cells within the immune system that’s responsible for regulating the destruction of other cells.

HLA genes are responsible for finding chains of viruses, bacteria, and tumour cells, assisting the immune cells in attacking and destroying foreign invaders. However, this collection of genes also brings the possibility of some versions (called alleles) directing the immune cells to attack the body’s healthy cells instead.


According to studies, the amino acids that assist in analyzing protein chains, called antigens, work both within and outside the immune cells and works to bind to other chains to determine if it’s an infectious organism or tumour cell. In healthy bodies, this means that the T cells within the immune system effectively remove these foreign chains and work to keep the body healthy in the process. However, certain alleles of the HPV genes, specifically the HLA-DR, HLA-DQ, and HLA-DP variations, have been strongly linked to the development of type 1 diabetes.


As for non-HLA genes, the IDDM2 gene in its variations within the DNA sequence has been connected to an increased risk for type 1 diabetes. Due to the gene’s connection with the insulin gene (INS), certain variations of the insulin gene can cause a decreased immune system response to insulin, causing the onset of diabetes type 1. However, many of these mutations with the insulin gene are considered rare. Within these variations, though, the IDDM2 gene can contribute towards a 10% increase in diabetes susceptibility due to the differences in gene repeatability and other alterations to the protein sequence.


Another reference made towards the connection between genes and type 1 diabetes is the CTLA4 gene, a gene that may be primarily involved with disease pathogenesis; however, while some studies have attempted to find variations of the gene linked to immune-related diseases, the direct relationship between the CTLA4 gene and type 1 diabetes isn’t clearly known due to the various environmental factors that impact genetic data. As researchers continue to attempt to narrow down the genetic variations and pathways associated with type 1 diabetes, the likelihood of developing diabetes also depends on its hereditary factors. Genetics and hereditary factors are similar but ultimately tackle different aspects of the same topic. For patients wondering about their risks of getting diabetes type 1, we will need to look into how type 1 diabetes impacts families from a hereditary point of view.


Is Type 1 Diabetes Hereditary?

While genetic factors can predispose people with type 1 diabetes, whether or not type 1 diabetes is hereditary is an entirely separate topic. Genetics plays a role in the development of the body’s basic systems and ultimately determines how DNA sequences form and vary when passed on through generations. But the inheritance of those genes depends on how those differ from person to person within families. For families, some members can have an increased risk of type 1 diabetes, while others may not present any of the usual factors that predispose people to type 1 diabetes.


Despite this difficulty, many organizations and research associations have attempted to narrow down how family genes can influence these risks, especially for children who are considered members with the highest risk of developing type 1 diabetes. To narrow down these risks, organizations such as Diabetes.co.uk and the American Diabetes Association work to define the risks through measures of probability, including:


Mothers with Type 1 Diabetes: Women with type 1 diabetes with children born before the age of 25 have a 1 in 25 risk, while those with children born after they turned 25 have a 1 in 100 risk. Overall, the risk for mothers passing on type 1 diabetes to their children ranges between 1% and 4%.


Fathers with Type 1 Diabetes: Men with type 1 diabetes with children have a 1 in 17 risks of passing on type 1 diabetes to their children, or 6%.


Both Parents: If both parents have type 1 diabetes, the risk of type 1 diabetes passing to those children increases, ranging between 1 in 10 and 1 in 4, or 10% to 25%. The risk also doubles if both parents developed diabetes before the age of 11.


Children: For children with parents who don’t have type 1 diabetes, brothers or sisters who have type 1 diabetes present an increased risk of 1 in 10, or 10%. Nonidentical twins with type 1 diabetes present a risk of 1 in 15 or 6.6%, and identical twins with type 1 diabetes have an increased risk of 1 in 2 ½ or 40%.

When it comes to the genetic components, these risk factors can also be affected by ethnicity. The HLA genes, including HLA DR3 and HLA DR4, have been shown to be more prominent in caucasian people, the HLA DR7 gene places African Americans at risk, and the HLA DR9 putting Japanese people at risk. These gene markers can make it more prominent for those to become predisposed to type 1 diabetes, increasing their risk overall and causing it to develop in certain individuals.


These statistics show that the closer the genetic variations are identical with one another, the higher the risk becomes. Nevertheless, there are certain cases where even families with those higher risk gene variations don’t develop type 1 diabetes. Certain syndromes, such as type 2 polyglandular autoimmune syndrome, thyroid disease, and poor adrenal glands, can also increase the risk. These statistics also vary according to the person’s ethical background, age, body weight, and other health factors.


Can Diabetes Type 1 Treatment Help?

As the rules of inheritance narrow down and predispose people to type 1 diabetes, diabetes type 1 treatment can be used to help raise awareness for this disease and help family members gain more insight into their risks. As an excellent prevention method, diabetic screening methods can help detect the early signs of this condition and help those predisposed to this condition seek further medical advice.


If you intend on getting tested for type 1 diabetes, your GP will perform various tests to measure blood glucose levels, kidney function, liver function, and cholesterol, all of which are important for narrowing down symptoms. These tests include:


C-Peptide Test: The c-peptide test measures if you have insulin resistance. This measurement for insulin resistance is often used for symptoms of hypoglycemia and other issues related to the pancreas. This is usually taken through a fasting blood test and measured.


Plasma Glucose Test: Also known as the fasting blood test, the plasma glucose test measures how much glucose is present in the blood. If the results are above 7.0 mmol/l, then the results are considered diabetic.


Oral Glucose Tolerance: An oral glucose tolerance test determines whether or not the body has difficulty metabolizing sugar and carbohydrates. Through this test, blood is taken, and sweet glucose drinks are given to measure the overall progression of glucose through the bloodstream.


HbA1c Test: Known widely, the HbA1c test measures haemoglobin in the blood but usually isn’t used for type 1 diabetes testing.


GAD Antibodies Test: A GAD antibodies test measures if the body is producing antibodies that destroy GAD cells or glutamic acid decarboxylase cells, which are considered essential for glucose conversion to energy. This is a widely used test for those with type 1 diabetes.


These tests should be used for those with family members with type 1 diabetes or are presenting symptoms that indicate signs of this condition. For those with those risks, these tests should be used at least once a year, and for children, they should have these treatments once every four months. Overall, it’s essential to speak with your GP or diabetic team for more information about this condition and help learn more about your risks for type 1 diabetes.


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