Is Type 1 Diabetes Genetic?

Type 1 diabetes¹ is an autoimmune condition in which the immune cells attack insulin-producing cells in the pancreas. It accounts for 5-10%² of all diabetes cases and is increasing worldwide, with over 30,000 Americans³ diagnosed yearly.

People diagnosed with type 1 diabetes cannot produce sufficient amounts of insulin, a hormone responsible for maintaining normal blood sugar (glucose) levels. If left untreated, this leads to insulin deficiency and can result in hyperglycemia⁴ (high blood glucose levels).

What is type 1 diabetes?

When you eat, your digestive system breaks down the food into glucose, which is absorbed into the bloodstream. This raises your blood glucose levels and prompts the pancreas to release insulin.

The insulin release helps absorb glucose in the blood by transporting it to cells throughout the body to use or store.

In type 1 diabetes, the pancreas cannot produce insulin. As a result, the body cannot regulate blood glucose levels, and glucose isn’t moved into cells. Over time, glucose builds up in the blood, and if left untreated, it can lead to two potential events:

• Hyperglycemia - This refers to high blood glucose levels that can rise due to insufficient insulin.

• Diabetic ketoacidosis - This occurs when the body can’t use glucose for energy and burns fat as an alternative energy source, causing ketones to build up in the blood. This complication is potentially life-threatening.

Signs and symptoms

The onset of type 1 diabetes occurs quickly, so it’s important to know the early warning signs and symptoms of type 1 diabetes. Symptoms vary between individuals, with the most common symptoms being:

• polyuria (increased urination)

• polydipsia (increased thirst)

• polyphagia (increased hunger) 

• severe weight loss

• Hyperglycemia

• diabetic ketoacidosis

How is type 1 diabetes diagnosed?

The main diagnostic tests used to diagnose type 1 diabetes are the glycated hemoglobin (HbA1c) test and the random blood sugar test.

Glycated hemoglobin (HbA1c) test

The HbA1c blood test⁵ is widely used to diagnose and monitor diabetes. The test measures your average blood glucose levels over the past two to three months. It’s reported as a percentage, where a higher percentage shows that increased glucose is attached to red blood cells.

A diagnosis of diabetes can be made if two repeat HbA1c tests produce a value of exactly or more than 6.5%.

Your doctor may opt for a random blood sugar test depending on your symptoms and known medical conditions.

Random blood sugar test

A random blood sugar test⁶ measures your blood glucose levels when the test is taken and does not require overnight fasting. A plasma glucose measurement equal to or greater than 200 milligrams per deciliter (mg/dL) suggests that you have diabetes.

This test needs to be repeated on a separate day or followed up with another test, such as:

• fasting plasma glucose test

• oral glucose tolerance test

Is type 1 diabetes genetic?

The causes of type 1 diabetes are unclear. However, researchers believe a strong genetic component is involved, which may also be accelerated by environmental factors. 

Some evidence⁷ suggests a family history of type 1 diabetes increases the risk of type 1 diabetes. Certain genes are also believed to affect your risk, with particular gene types accounting for 30-50%⁸ of the genetic risk for type 1 diabetes. 

Genetic risk factors for type 1 diabetes

Family history

In the general population, the overall risk of developing type 1 diabetes is 0.4%⁹. However, people with a family history of type 1 diabetes have a higher risk of developing the condition. 

The odds of developing type 1 diabetes change depending on the family member, as seen in the table below:

Gene families

Type 1 diabetes occurs due to the autoimmune destruction of insulin-producing pancreatic cells. Researchers¹⁰ believe this may result from genetic mutations, which can cause genes to be expressed abnormally or not work correctly. 

This can impair the immune system’s ability to recognize its own activity and leads to autoimmune attacks. Over 60 genetic regions are associated with the genetic risk of type 1 diabetes.

Major histocompatibility complex 

The major histocompatibility complex¹¹ (MHC) is a group of genetically-coded molecules ​​that helps the immune system recognize foreign cells. In humans, the MHC system is known as the human leukocyte antigen¹² (HLA) complex. 

Human leukocyte antigen complex

The HLA complex is a group of genes that helps the immune system recognize the body’s own proteins and foreign cells, such as bacteria and viruses. The HLA complex is vital to the immune response and accounts for 50% of the familial risk for type 1 diabetes. 

Two cell surface receptors, HLA-DR and HLA-DQ, are believed to be strongly associated with type 1 diabetes. These receptors help present foreign cells to white blood cells. However, certain variants may alter the function of these genes. 

Approximately 90% of type 1 diabetes patients are believed to carry at least one variation of the HLA-DR or HLA-DQ cell receptor gene compared to 40% of the general population that do not carry either.

Research is ongoing to understand how these genes may affect the immune response in type 1 diabetes. 

Insulin gene

The insulin (INS) gene¹³ accounts for 10% of genetic risk in type 1 diabetes. This gene is found in the insulin-producing pancreatic cells and instructs the body to make insulin to maintain blood glucose levels. 

Research⁸ has shown that children with a family history of type 1 diabetes and HLA-risk genotypes were associated with a 1 in 5 chance of diabetes development compared to children with no family history of diabetes with the same gene (1 in 20 risk). 

Cytotoxic T-lymphocyte antigen 4

Cytotoxic T-lymphocyte antigen 4 (CTLA-4)¹⁴ is a protein found on T cells (immune cells) that acts as an immune checkpoint to prevent T cells from killing noninvasive cells. Changes to how CTLA-4 is modified after it has been made may influence the risk of type 1 diabetes onset. 

This gene has also been strongly linked to people with both thyroid autoimmunity problems and type 1 diabetes, suggesting that the thyroid also contributes to type 1 diabetes onset. 

Protein tyrosine phosphatase nonreceptor type 22

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22)¹⁵ is a gene that contains instructions to produce a protein that stops spontaneous T cell activation.

While PTPN22 is not a direct risk factor for type 1 diabetes onset, a mutation in this gene may promote the survival of autoreactive immune cells and reduce normal communication between T cells and their receptors.  

Testing

Autoantibody test

An autoantibody test can be used to confirm if the development of type 1 diabetes is autoimmune. Autoantibodies are proteins produced by the immune system in response to the body’s own tissues and cells. 

These are different from antibodies, which respond to foreign substances circulating in the blood. 

The test looks for four autoantibodies that indicate the body’s autoimmune response. These are: 

• ​​insulin autoantibodies (IAA)

• glutamic acid decarboxylase autoantibodies (GADA)

• islet cell cytoplasmic autoantibodies (ICA)

• insulinoma-associated-2 autoantibodies (IA-2A) 

A high amount of one or a combination of these autoantibodies suggests that you have type 1 diabetes or an increased risk of developing it. Test results vary depending on several factors, so it’s best to talk to your doctor about what these results could mean for you. 

C-peptide test

The C-peptide test¹⁶ measures C-peptide, a byproduct of insulin formation, to determine whether you are producing insulin or if you need to rely on an external source (i.e., an insulin pump or injections). 

This test can also be used to determine which type of diabetes you have. 

A C-peptide test may be given as a blood or urine test. For a C-peptide blood test, you may need to fast eight to 12 hours before your test. However, you don’t need to do this for a C-peptide urine test. Talk to your doctor in case they have specific instructions. 

A normal physiological C-peptide range in the fasted state is 0.9 to 1.8 ng/mL. Ranges lower than this may suggest your pancreas is producing little to no insulin. However, this may be normal if your blood sugar is low and you have fasted for the full 12 hours. 

If your blood sugar is high but your C-peptide result is low, this may indicate type 1 diabetes. Alternatively, if your blood sugar is low but your C-peptide result is high, this suggests that your pancreas is making too much insulin. 

Other causes of type 1 diabetes

Although genetics plays a part in type 1 diabetes development, evidence suggests that the environment also plays an essential role. Some factors believed to play a role include: 

• viral infections - Enteroviruses (a common virus group responsible for mild illnesses) are believed to contribute to type 1 diabetes development. One study showed that they’re strongly associated with the development of pancreatic islet autoantibodies in 140 American children. While it’s unknown how the viruses lead to type 1 diabetes onset, it could be related to the activation of autoreactive immune cells.

• hygiene - Inspired by the hygiene hypothesis¹⁷ proposed by David Strachan, research suggests that the increase in type 1 diabetes cases is related to a lack of exposure to certain bacteria and microbes. These microbes may strengthen our immune system against certain diseases.

• seasonal variation - Reports¹⁸ suggest that the birth month or the month of type 1 diabetes diagnosis may be related to type 1 diabetes onset. This might be due to a variation in the amount of vitamin D received by both mother and child during the change in seasons.

How to treat type 1 diabetes?

All people diagnosed with type 1 diabetes require insulin therapy¹⁹. This involves receiving injections several times daily or through a continuous insulin pump.

Different types of insulin therapies work differently and at various rates. Your doctor will discuss these options with you.

When discussing insulin therapy options, keep the following terms in mind:

• onset -  the time taken for insulin to reach your bloodstream and lower blood glucose

• peak - the time when the insulin is working at max effort

• duration - the time taken for insulin to lower your blood glucose

Management

Effectively managing your type 1 diabetes helps you minimize the risks of major diabetic complications. One of the most important management strategies is frequent blood glucose monitoring. 

Your doctor will likely give you a range of numbers to maintain your blood glucose levels, so it is important to record your results to adjust your insulin doses accordingly. 

To check your blood sugar levels, you need:

• a blood glucose meter - This provides a blood glucose level value.

• a lancet device with lancets - These prick skin for blood glucose monitoring.

• blood glucose strips - These are inserted into the blood glucose meter for a blood glucose reading. 

Make sure to record all the blood glucose values in a book, as this helps your doctor determine your next course of action. 

Other strategies to manage your type 1 diabetes include: 

• keeping a record of special events that may affect your blood glucose and insulin intake

• creating a well-balanced and nutritional food plan to suit your needs

• incorporating regular exercise into your routine

• getting all your vaccinations to reduce the risk of diabetic complications

• understanding how to balance insulin dosing, exercise, and food intake 

How to prevent type 1 diabetes

Currently, type 1 diabetes cannot be prevented. Furthermore, without understanding the causes of type 1 diabetes, it’s difficult to understand whether type 1 diabetes is preventable.

If you have type 1 diabetes, the best way to control complications is to monitor your blood glucose levels continuously and to receive insulin on time.

The lowdown

Type 1 diabetes is an autoimmune condition that occurs when immune cells destroy insulin-producing cells in the pancreas, leading to hyperglycemia or diabetic ketoacidosis. Although it’s not fully understood why type 1 diabetes occurs, researchers believe genes, family history, and the environment are potential risk factors.

Currently, type 1 diabetes is treated with insulin therapy. No prevention strategies exist for type 1 diabetes. However, if you have type 1 diabetes, maintaining a balanced lifestyle and frequently monitoring blood glucose levels will significantly reduce the risk of diabetic complications. It’s recommended to speak to your doctor to develop a personalized plan to help you manage type 1 diabetes.