Genomics 101

Genomic101 Deep Dives - Type 1 Diabetes (T1D)

Want to learn more about some of the conditions on our panels? Look no further than our 'deep dives' series!

Shari
Dec 21, 2023

Series Overview:  GenomicMD’s Deep Dive blog series is designed as a casual guide on the journey to better understanding the many details associated with medical conditions on our test panels. Our hope is that this knowledge empowers our readers to start conversations with their healthcare teams about taking proactive measures which can lead to longer and healthier lives. If this sounds interesting to you, please read along as we dive deeper into the subject of diabetes (Type 1 in particular) and learn more about its biology, symptoms, genetic links, and impact on the human body.

**Please note that our Deep Dives blog series is not intended to be an exhaustive resource, but rather a small window into the knowledge available on the diseases we cover on our test panels. Our goal is to assist patients in learning more about these conditions in order to establish a conversation with their healthcare providers, and as such these blogs should not be taken as medical advice. Please discuss any concerns or personal risks associated with the diseases found in this series with your healthcare team.


A Genetic Deep Dive: Type 1 Diabetes (T1D)

37 million. 1 in 10. These numbers represent the US population currently diagnosed with diabetes. Beyond these statistics, studies suggest that there may be approximately 28.7 million more people who remain undiagnosed - so chances are you know somebody who is currently living with this condition. Most people know that diabetes has something to do with ‘blood sugar,’ but beyond that, understanding can get a little fuzzy–especially when it’s time to break it down into ‘types’. Our last Deep Dive was focused on explaining the cause and effect of Type 2 Diabetes, so today we will seek to round out our diabetes education with a thorough review of Type 1, which is a highly impactful condition that affects an estimated 5-10% of the total diabetic population in the United States. Though these two diseases are similar in that they both involve issues with insulin production, they are also quite different–so let’s get started!

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Diabetes is a ‘blood sugar’ disease - but what does that mean, exactly? To start, let’s review some basics that we learned from our previous review of T2D. Glucose is a type of sugar that our bodies use as a source of energy. The human body carefully maintains very specific levels of glucose in the bloodstream to ensure it is functioning well at all times. Any time an organ is in need of an energy boost, it uses a hormone created in the pancreas called insulin to transfer this glucose from the bloodstream into its individual cells. When this happens, the bloodstream’s glucose levels naturally dip, so another pancreatic hormone-glucagon-jumps in to help the body raise those blood glucose levels back up. It does this using fancy tricks like telling the liver to convert its stored glucose into a usable form that can be released into the bloodstream. This delicate dance between insulin and glucagon is essential for healthy metabolic function in our bodies, and it ensures that we are able to maintain enough glucose in the bloodstream to be prepared for any sudden demands for energy. 

So, how does all of this information relate to diabetes, why are there multiple types, and what actually causes it? (I’m glad you asked!) Diabetes can be caused by a number of breakdowns in a step in this ‘insulin to energy’ process, including:

    1. The pancreas being unable to create ENOUGH insulin to properly support the body’s processes (T2D)

    2. The pancreas is able to make insulin, but the body becomes resistant to it and is thus unable to use it (also T2D)

    3. The pancreas being unable to make any insulin at all (This is Type 1 Diabetes, and is what we will be discussing today!)

Type 1 Diabetes is considered an autoimmune disease. This means it is caused by the affected person’s immune system becoming confused and attacking healthy insulin-producing cells in the pancreas instead of the pathogens (micro-organisms like bacteria and viruses which can cause disease) it is meant to attack. To put it simply, for people with Type 1 Diabetes the body’s immune system causes it to be unable to produce ANY insulin at all, which means that glucose is unable to be removed from the bloodstream without medical intervention. The precise reasons or triggers for this autoimmune response are still unknown, which means that risk factors for Type 1 Diabetes are much less clear than those for Type 2 Diabetes--but, there is research being done into whether there are any underlying genetic or environmental triggers.

Actionability Factors (why is knowing your risk important?): 

All of the issues listed above lead to an improper amount of glucose in the bloodstream. This can cause damage to blood vessels, resulting in: 

  • Short term complications such as:
    • Diabetic Ketoacidosis.
      • This is caused by the body not producing enough insulin to allow glucose (blood sugar) into its cells for use as energy. When this happens, cells are deprived of nutrition they need to function, so the body must instead break down muscle and fat for the energy it needs. This process produces acids in the blood called “ketones,” which can build up to dangerous levels in the body. Diabetic Ketoacidosis is a serious condition which requires immediate medical intervention and can result in long-term damage to the body or even death, if left untreated. 
  • Long term complications such as:
    • Gum Disease
    • Heart disease
    • Stroke
    • Blindness (caused by blood vessel damage in a part of the eye called the retina), cataracts, and/or glaucoma.
    • Chronic kidney disease and kidney failure requiring dialysis if not treated in early stages
    • Nerve damage (neuropathy) - this causes numbness and pain, usually in the legs and feet
    • Amputation-if blood vessels are damaged from diabetes, it can lead to infections severe enough to require the amputation of limbs

Because of the damage high levels of blood sugar can have on different body systems as listed above, it is incredibly important to take action under the guidance of a healthcare team to maintain proper treatment of T1D to prevent both its acute (immediate) and chronic (long-term) complications.

Type 1 Diabetes Risk Factors:

This series typically breaks down disease risk factors into the categories of “modifiable,” or things you can control, and “non-modifiable,” or things you cannot control. However, beyond understanding that T1D is an autoimmune condition. there is a high level of scientific uncertainty regarding its exact cause. As you can imagine, this really limits our understanding of what to look out for when determining one’s own risks. Though much is still unknown about T1D, we do know the following things can factor into the risk of developing of this condition:

  • Age: T1D can develop at any age, but it is most commonly diagnosed in children, teens, and young adults
    • Children between the ages of 4 and 7, as well as those between the ages of 10 and 14 years old are at higher risk to develop this condition.
  • Family history of diabetes (especially Type 1) or other autoimmune conditions
    • There is around a 15-fold increased risk for relatives of patients with T1D, or more specifically:
    • 1-4% increased risk for children of mothers with T1D
    • 6-9% increased risk for children of fathers with T1D
    • 6-7% increased risk for siblings of those with T1D
  • Ancestry: those of European ancestry are more likely to develop T1D

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The precise causes and triggers of T1D are still unknown. However, current research suggests that certain genetic variants might make people more prone to develop this condition. Though there are no directly proven environmental or genetic triggers, researchers continue to look for specific molecules, viral infections and other environmental and/or behavioral factors that may contribute to Type 1 Diabetes risk.. Because of the uncertainty of the root causes of T1D and its risk factors. prevention tactics are much more difficult than when compared to T2D.

Family History Considerations:

One of the main known risk factors for T1D is having a family history of the disease.  If a person’s biological siblings or parents have been diagnosed with T1D, they are more likely to develop the disease as well. This is believed to be due to two main causes: inherited genetic variants or risk (which we have explained in past blogs) and shared environmental & behavioral factors, which may ‘trigger’ the disease to develop.

Polygenic Risk Assessment (PRA) Considerations:

As discussed in previous Gen101 blogs, a polygenic risk assessment is a numerical score that is calculated based on your personal genetic information, and it can estimate your specific genetic risk of developing certain diseases. In regards to T1D, recent studies have pointed towards the utility of PRS as both an independent and collaborative source of information on diabetes risk. Studies have shown that its use alongside integrative methodologies (such as serum metabolites) and other clinical variables can help predict future risk and improve already existing models of conventional Diabetes care. There are even studies that suggest PRS may be able to help clinical teams differentiate between T1D and T2D for individuals presenting with overlapping symptoms of both, when used alongside current diagnostic methods.

Other Notable Genetic Variants:

Some people may inherit certain genetic changes (variants), in genes such as HNF1A, GCK, HNF4A, or HNF1B, which can cause a condition called “MODY” (Maturity-onset diabetes of the young). MODY is characterized by abnormally high blood sugar levels and earlier onset (typically before age 30), and it is estimated to account for 1-3% of all cases of diabetes. Patients found to be at high risk for MODY should speak with their healthcare team about whether additional genetic testing may be appropriate for them.

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Here are some things to consider when examining the prevention, symptoms, and diagnosis of Type 2 Diabetes.

Prevention:

  • Because of the previously-stated uncertainty of the root causes of T1D, there are no known methods of prevention for this condition.

Symptoms:

In broad terms, the symptoms of T1D are incredibly similar to those of T2D. The main difference between the two is that these issues typically develop slowly over time for Type 2, but can emerge quickly (in a matter of days or weeks) with Type 1. These symptoms include:

  • Excessive thirst or hunger
  • Excessive urination
  • Increased fatigue
  • Unexplained weight loss
  • Blurred vision 
  • Slow healing of cuts/sores or frequent infections
  • Frequent penile or vaginal thrush

Diagnosis:

For years, T1D was considered mainly a childhood onset condition. Because of this and its many overlapping symptoms to Type 2 Diabetes, misdiagnosis in adult cases was not uncommon in the past. In recent years, however, it has become more well-known that adults can also be newly diagnosed, leading to less cases of both misdiagnosis and improper treatment of adult-onset T1D. The diagnostic process for T1D may include:

  • A Glycated Hemoglobin test, also called an “A1C” test.
    • This test can provide an estimate of a person’s blood sugar levels for the previous 2-3 months. 
    • A level over 6.5% is considered diabetes.
  • A Fasting Plasma Glucose (FPG) blood level test. 
    • A level over 126 mg/dL is considered diabetes.
  • An Oral Glucose Tolerance Test (OGTT)
    • This test checks blood glucose levels before and after drinking a sugary drink. 
    • A result of 200 mg/dL or higher is considered diabetes.
  • An Autoantibodies test
    • This tests for Insulin Autoantibodies (IAA) in the blood. Autoantibodies are what erroneously attack healthy tissues and cells, and these are a sign of autoimmunity found exclusively in T1D

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Living With T1D

The primary goal of any diabetes management technique is to keep blood sugar levels within the appropriate range for any given person. This can be done using a combination of methods, including but not limited to dietary modifications, lifestyle changes (e.g. exercising regularly), monitoring, and medications.

Common Medications

The most common medication required by a Type 1 Diabetic would be insulin. There are different types of insulin that work at different speeds, and many people end up using a combination of fast-acting insulin and a slower, ‘long’-acting one, depending on current blood sugar levels. Insulin is administered subcutaneously (under the skin), either by needle and syringe, insulin pen, or an insulin pump. 

Besides insulin injections, other medications may be prescribed by healthcare providers to assist with health maintenance outside of direct diabetes care. These include, but are not limited to, high blood pressure medications, aspirin, cholesterol-lowering drugs, etc. While these are not directly considered “Diabetes medications,” they may be prescribed to help with related healthcare issues that can affect Diabetes management.

Technology and T1D Management

Recently, the use of Remote Patient Monitoring (RPM) technology has emerged as a way for healthcare providers to monitor a patient’s condition remotely, rather than needing frequent in-person clinic visits. Common RPM’s for T1D include glucose monitors and insulin pumps that can transmit blood sugar data to a healthcare team in real time.

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  • It is estimated that around 16% of the world’s diabetes cases are T1D
    • That is about 8.4 million individuals worldwide!
  • 5.7% of all US adults with diagnosed T1D report using insulin to maintain their blood sugar levels
  • Researchers estimate that those with diabetes have: 
    • A 9% higher risk of developing cancer 
    • A higher risk of developing circulatory and other heart conditions.
    • Medical expenditures up to 2.3-times higher than those without diabetes

conclusion

As we conclude our deep dive into the world of T1D, our hope is that this knowledge empowers you to engage with your healthcare team, ask informed questions, and make empowered choices when it comes to your health. Although the causes and triggers of T1D are still unknown, researchers continue to investigate the best ways for people to live full and healthy lives with this autoimmune condition. Stay tuned for more explorations into the conditions that make up our panels with our next installment of GenomicMD's Deep Dives.

glossary2

Diabetes - A chronic condition wherein the body is unable to regulate its insulin production properly, resulting in elevated glucose (blood sugar) levels which (when left untreated) can cause damage to other organ systems.

Insulin - A hormone produced in the pancreas which regulates the amount of glucose (blood sugar) in the blood. Lacking insulin in the body can cause a form of diabetes.

Glucagon - A hormone produced in the pancreas that works together with insulin to regulate glucose (blood sugar) in the body.

Glucose - a simple sugar that is an important energy source for living organisms.

Autoimmune disease:  Type of disease characterized by the immune system mistakenly attacking healthy cells in the body.

Pathogen - microorganisms like virus and bacteria that can cause harm to the body

Autoantibodies : Antibodies made by the body that targets the person’s own cells and tissues, the cause of some autoimmune diseases.

Diabetic Ketoacidosis (DKA): A serious condition caused by the body not producing enough insulin to allow glucose (blood sugar) into its cells for use as energy. When this happens, cells are deprived of nutrition they need to function, so the body must instead break down muscle and fat for the energy it needs. This process produces acids in the blood called “ketones,” which can build up to dangerous levels in the body.

Ketones: Chemical produced when the body breaks down fats for energy in the absence of glucose. Too high levels of ketones can lead to DKA and excess acid in the body. 

Maturity Onset Diabetes of the Young (MODY) - A diabetic condition characterized by abnormally high blood sugar levels and an earlier onset (typically before age 30). It is estimated to account for 1-3% of all cases of diabetes. 

Polygenic Risk Assessment (PRA) - This is a generic term that can be used to describe various methods of polygenic testing like GRS (Genetic Risk Scores), PGS (Polygenic Scoring or Screening - not to be confused with Preimplantation Genetic Screening for embryos), PRS (polygenic risk scores), PRI (Polygenic Risk Index), and PSPGS (Population Standard PGS); these types of genomic tests compile the risks of up to millions of small, mostly mild to moderate genetic variants called SNPs to quantify one’s individual lifetime risk of developing a particular disease or condition.

Glycated Hemoglobin (A1C) Test - A blood test that reveals the average blood sugar level over a period of two to three months. A normal level is below 5.7%.

Fasting Plasma Glucose (FPG) test - A blood level test used to diagnose diabetes. A level over 126 mg/dL is considered diabetic.

Oral Glucose Tolerance Test (OGTT) - This test checks blood glucose levels before and after drinking a sugary drink. A result of 200 mg/dL or higher is considered diabetic.

Remote Patient Monitoring (RPM) - a term encompassing the ability of healthcare providers and patients to monitor and manage their condition from their own homes, often enabled by the use of technology.

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Websites:

Journals:
Genomics 101 Deep Dives Polygenic Risk Assessments Diabetes

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