What can genetics tell me about my Type 2 Diabetes risk?

What can genetics tell me about my Type 2 Diabetes risk?
Type 2 diabetes is a chronic disease where the body cannot utilize insulin properly. Cells throughout the body become less responsive to insulin signals, or the pancreas produces too little insulin, or both, causing high levels of sugar to stay in the bloodstream. Whether you have a family member with Type 2 diabetes or you’re curious about what the latest science has to offer, let’s understand let’s understand what’s currently possible to detect through genetic testing.
Written by Dave Gennert, PhD candidate
Orchid offers advanced genetic testing for couples who want their child to have the best shot of a healthy life. “Genetics for Humans” is where we unpack how genetics impacts our everyday lives and the latest tools to help you build a healthier family.

What is Type 2 diabetes, and how does it impact individuals?

Diabetes, in general, is characterized by high levels of glucose, or sugar, in the blood. The cells throughout the body use the blood’s glucose to function properly, but they need the help of the hormone insulin to actually absorb it. Sustained elevated blood glucose levels can lead to a variety of serious complications, such as eye disease, foot problems, and kidney disease. These are primarily caused by blood vessel and nerve damage.

As opposed to Type 1 diabetes, Type 2 diabetes (T2D) can largely be managed and prevented through medication and lifestyle changes. Maintaining a healthy diet, weight, and increased physical activity level are some of the most effective ways to prevent diabetes.

How common is Type 2 diabetes?

Globally, the number of people with diabetes has been dramatically rising over the past several decades, growing from 108 million in 1980 to 422 million in 2014. T2D has been estimated to cause 1.6 million deaths annually, making it the seventh leading cause of death in the world. In America alone, roughly 34 million people, or 1 in 10, have diabetes. Between 90-95% of those cases are Type 2 diabetes. Rates of diabetes also vary by ethnic group, with higher rates in Hispanic Americans (12.5%), Black Americans (11.7%), and Native Americans/Alaska Natives (14.7%), due to both socioeconomic and genetic predisposition.

Does diabetes run in families?

A family history of T2D is a strong indicator for assessing the risk of developing the condition. Studies have shown that individuals with a first-degree relative (parent, full-sibling) with diabetes are 2.3 times more likely to develop it themselves, too. Having multiple first-degree relatives with diabetes increases risk by 5.5-fold. Through these risk criteria, about 1 in 4 individuals have a moderately increased familial risk and 1 in 13 have a high familial risk of diabetes.

In twin studies, researchers found a high correlation between twins that either both have T2D or both did not. For a twin with T2D, their twin sibling also developed T2D 20-53% of the time. Sometimes, correlation does not always imply causation though, and lifestyle habits greatly impact overall risk. One study found that if only one twin was affected by T2D, the affected twin was 3 times more likely to live a sedentary lifestyle than the other twin.

These studies demonstrate that genetics plays a significant role in a person’s risk for type 2 diabetes, but lifestyle factors, such as diet and exercise, can modulate that risk.

Is there a single genetic cause for Type 2 diabetes?

For the vast majority of people that develop diabetes, no, a single gene or mutation is not the ultimate cause.

However, roughly 5% of diabetes cases are due to single-gene disorders, collectively called Maturity-Onset Diabetes of the Young, or MODY. Mutations that cause MODY can appear in over a dozen different genes, with the physiological effects, severity, and treatment options dependent on which gene is affected.

But most people who experience T2D do not have any single gene mutations. Like many other polygenic (or “many-gene”) diseases, the genetic basis of diabetes is a combination of many genes and genetic markers that together add up to a significant level of genetic risk.

Scientists have only recently developed the technology and capability to analyze the genomes of enough people to assess these risk-elevating genetic variants across the genome and determine the amount of increased risk they confer.

Is there a genetic test for Type 2 diabetes?

Yes, there is now a way to measure your genetic predisposition to T2D. This is different from a diagnosis, however. Genetic screening can tell you if you are more or less likely to develop T2D than the average person based on your genetic background.

This is done by factoring in all the variants across the genome that we know increase risk. These genetic variants were found by comparing the genetic makeup of tens of thousands of individuals diagnosed with T2D (“cases”) with individuals who have not (“controls”).A recent study using data from over 400,000 individuals found that 3.5% of people have a three-fold higher risk of T2D than the general population.

Other studies have found that combining genetic screening with established clinical risk factors for T2D, such as family history and blood glucose levels, increases the predictive ability to assess overall risk for T2D.

With Orchid’s advanced genetic testing, you can get a sense of your genetic predisposition to T2D and remove some of the guesswork on what you can pass on to your future children.

What actions can I take based on the information from a genetic test for Type 2 diabetes?

If you or your future child has an elevated genetic risk for Type 2 diabetes, the risk of developing T2D at some point in life can be over three times higher than in the general population.

The useful thing about your results is that if you identify certain genetic vulnerabilities that can impact you or your future children, you can potentially do something about it and mitigate these risks. Ways you can act on your results include:

  • Offset genetic risks with healthy lifestyle choices.  Lifestyle interventions are the most powerful tool we have to prevent T2D. This has been well studied and established — researchers found that increased physical activity and weight loss led to a 58% reduction in the incidence of T2D compared to no lifestyle change.  This was an even greater decrease in risk than taking preventative medication.  Diet and exercise can go a long way in preventing T2D, especially for those with elevated genetic risk.
  • Consider regularly screening for your glucose levels.  Diabetes is often preceded by prediabetes, characterized by a moderate increase in blood glucose, detectable by several types of blood tests — from hemoglobin A1c levels, fasting glucose levels, to continuous blood glucose monitoring.  Monitoring for prediabetes can help detect an abnormal insulin response before serious complications arise.  Starting lifestyle and medication interventions early will help prevent progression into T2D.
  • Embryo screening to reduce your child’s potential genetic risks. Embryo screening allows you to assess each embryo’s genetic risk for T2D and other common conditions. This allows you to prioritize the transfer of embryos with the lowest genetic risk and thus reduce your future child’s genetic risks.

Key takeaways

  • T2D is a common metabolic disease, representing the seventh leading cause of death worldwide, affecting an increasing number of people both worldwide and in the US.
  • Genetics and lifestyle can predispose a person to developing T2D, while diet, weight management, and exercise interventions significantly reduce that risk.
  • Advanced genetic testing can now quantify the genetic component to T2D for you and your family.
Resources 
Orchid offers advanced genetic testing for couples planning on building their family. We use advanced tools and smart, caring humans to help you give your future children the best shot of a healthy life. Conceive with greater confidence and peace of mind
2/2/2021
Genetics
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