Does DNA Affect Diabetes? What to Know About Diabetes and Genetics

Is diabetes genetic? If you or a loved one have recently been diagnosed, this question may have crossed your mind. Diabetes is a complex condition that does not have one single cause. However, it is true that some people inherently have a higher risk of developing diabetes.

What increases this risk? Is there a link between diabetes and genetics? If you have diabetes, you might wonder whether your child could get it too. Or perhaps someone else in your family has it, and you wonder what that means for you.

Discovering whether diabetes is genetic or not is a good place to start, and we’re going to take you there so that you know the healthiest decisions to make in the future.

Although you will discover that a relationship exists between diabetes and genetics, there is no such thing as a “diabetes gene” that some people have and others simply don’t.

There is a distinct difference, however, between a so-called “diabetes gene” and genes that can contribute to diabetes. Some genes do contribute to factors that can ultimately result in diabetes, and these genes can be passed down.

Let’s examine the types of diabetes and some genes you should know about so you can better understand your body and make healthy choices.

Over 1 million Americans have type 1 diabetes, and many of those 1 million are children. Let’s take a look at type 1 diabetes and how genes play a role.

To start, let’s define type 1 diabetes. Type 1 diabetes is when the body’s own immune system attacks the cells in the pancreas that make insulin—a hormone we need in order to help blood sugar get into our cells for energy purposes.

When our pancreas produces little or no insulin, there is nowhere for the sugar to go. This results in sugar building up in the bloodstream, which is why people who have type 1 diabetes need injections of insulin to bring their blood sugar levels down. It is crucial the balance is maintained so that there is not too much or too little glucose or insulin.

HLA (human leukocyte antigens) genes encode molecules that are critical to our immune systems. These molecules hold tiny chains of amino acids on the cell’s surface, and immune cells analyze the chains. When the immune cells find a suspicious chain, they begin attacking it with the intent of protecting us. Without these HLA genes, our immune cells wouldn’t be able to find or fight off the appropriate chains of bacteria, viruses, or even tumor cells.

On the other hand, inheriting certain variants of HLA genes increases the chances that these immune cells will attack the body's healthy cells instead of just the harmful ones. This is how a region called IDDM1—a part of the human genome that influences type 1 diabetes risk—contributes to the immune attack of our crucial pancreatic beta cells—the cells responsible for producing insulin.

An autoimmune disease is when the immune system mistakenly sets out to destroy the body's own tissues, causing more harm than good. The risk of developing this condition is linked with the specific variants of HLA genes present in the body. Type 1 diabetes is unique among these types of diseases in that certain HLA variants may increase the risk of Type 1 diabetes. Researchers are using this information and other analyses about the connection between diabetes and genetics to learn how to predict someone’s odds of getting diabetes during their lifetime.

For instance, most caucasian individuals with type 1 diabetes have the HLA-DR3 or HLA-DR4 genes. If both a person and their child are white and share these genes, that child's risk is even higher. Alternatively, the HLA-DR7 gene may put African Americans at a higher risk, whereas the HLA-DR9 gene may put Japanese people at a higher risk.¹ More studies are being done to further explore this phenomenal pattern.

For a deeper dive, let’s revisit those HLA genes that encode major histocompatibility complex (MHC) proteins.² There are two main classes of MHC proteins. Both classes display chains of amino acids. These chains are called antigens, and they are analyzed by T cells. T cells may have the most critical role of lymphocytes in our immune systems, as they activate other immune cells such as killer T cells (which do just as the word implies: kill anything the body deems necessary to protect itself).²

If T cells bind to the chain found on an MHC, the T cell will immediately launch a powerful attack by tricking our other immune cells into thinking it is helping the body. The body ideally only contains T cells that bind to chains from viruses, bacteria, other infectious organisms, and tumor cells. While this ideal is typically achieved through a child’s healthy development, the alternative is found in autoimmune diseases like diabetes. In these cases, T cells do the exact opposite of what they should and bind to chains from the body's healthy cells.

HLA genes have many different variants, which leads to many different variants of MHC proteins and allows a large variety of chains to be presented to cells. When someone inherits particular HLA variants, this can account for more than half of their genetic risk of developing type 1 diabetes.³

Some individuals do have certain genes that make them more likely to develop type 1 diabetes in their lifetime. Luckily, many of these predisposed individuals won’t end up actually getting diabetes. Although there are still many unknowns about type 1 diabetes, it is thought that being exposed to a trigger in the environment—such as an infection or virus—can play a part in developing the condition.

It’s important to note that diet and lifestyle habits do not cause type 1 diabetes. The risk factors for type 1 diabetes are not quite as clear to experts as they are when it comes to prediabetes or type 2 diabetes—but the undeniable relationship between diabetes and genetics remains.

At this point in time, healthcare professionals and scientists are sure of certain risk factors, including immediate family history—such as having a parent or sibling with type 1 diabetes. Although you can develop type 1 diabetes at any age, it’s more likely to get it as a child, teen, or young adult.

In the U.S., white people are more likely to develop this type of diabetes than Latinos and African Americans. We also know that the disease is less common in people who—during infanthood—began eating solid foods at later ages.

More than 100 million Americans currently have diabetes or prediabetes. Because so many are at risk of developing this condition, let’s look at what it is and how your genetic makeup affects your predisposition.

With type 2 diabetes, your body doesn’t use insulin properly. In this case, the pancreas will try to produce more and more insulin in hopes that it will take hold—but the cells, unfortunately, do not respond to it. This insulin resistance results in higher-than-normal blood sugar levels.

Some known risk factors in developing type 2 diabetes are:

• Having a poor diet and being overweight
• Not exercising enough (for instance, exercising less than three times per week)
• Having an immediate member of the family who’s been diagnosed with type 2 diabetes
• Being over the age of 45
• Having prediabetes
• Having gestational diabetes or having a baby that is over 9 pounds
• Your race or ethnicity (for example, being Hispanic or Latino American, African American, Alaska Native, or American Indian makes you a higher risk)

These indicate that there is, indeed, a correlation between diabetes and genetics.

TCF7L2 is involved in Wnt signaling—a group of signal transduction pathways beginning with proteins that pass signals to cells through receptors on the cell surface—and is the most important type 2 diabetes susceptibility gene that has been identified thus far.⁴ The TCF7L2 gene has common intronic variants (variants that can alter the splicing of a gene and disrupt the gene sequence) strongly associated with diabetes in every major racial group.

This gene mediates the effect of free fatty acids, which affects how well pancreatic beta cells function. Research suggests that genetic variants within the TCF7L2 gene impair insulin and glucagon metabolism.⁵ This results in impaired glucose sensitivity, which is further hindered by a high intake of fats.

Several clinical trials have identified even more genes and gene variants associated with a person's risk of developing type 2 diabetes—including KCNJ11, CDKAL1, WFS1, PPARG, FTO, and T2DM.⁶ This information helps us understand the link between diabetes and genetics even further. While some genes have a direct association with the development of diabetes, some contribute to a person’s risk by influencing other physiological processes in our bodies.

Take the fat mass and obesity-associated (FTO) gene, for instance. Common variations in the FTO gene have been linked to a higher BMI, obesity, and even the regulation of eating patterns and expenditure of energy. Research also tells us that certain variations in the FTO gene are associated with an increased risk of type 2 diabetes. However, this effect can depend on differences in BMI.⁷

Type 2 diabetes has a stronger connection to family history than type 1 does. Studies of twins, in fact, have shown that genetics play a significant role in the development of type 2 diabetes. However, your individual risk also depends on environmental and lifestyle factors. Obesity, for example, tends to run in families—and more often than not, families develop similar eating and exercise habits. Therefore, if you have a family history of type 2 diabetes, it could be difficult to figure out whether your diabetes is actually due to genetic susceptibility or to lifestyle factors.

Diabetes is likely the result of a combination of factors. Genetic variants alone don’t determine whether you will develop diabetes, but they do play a role. For example, identical twins have identical genes—yet if one of the twins has type 1 diabetes, the other also has about a 50 percent chance of also being diagnosed. On the other hand, when one twin has type 2 diabetes, it is about 75 percent likely that the other twin will also be diagnosed.⁸

While we now know that there is a correlation between diabetes and genetics, studies show that certain lifestyle changes can lead to delaying or preventing the disease.⁹ Diabetes is a serious health condition, but knowing what your DNA says about your risk can help you make informed health decisions.

GenoPalate cannot specifically diagnose or give information on your predisposition to diabetes. We are here to tell you that, even with an increased risk, you can still make lifestyle changes that can improve health outcomes. If making healthy modifications seems overwhelming, not to fear—we can help guide you in how to do that.

If you’re ready to take control of your health, read our article “Can a DNA Test Really Tell You How to Eat?” to learn more about how your DNA can help you navigate making smarter eating choices. This guide can help you understand the connection between diabetes and genetics as well as how DNA ties into many other aspects of health so you can ultimately be guided toward the healthiest path.

References

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3. Todd JA, Bell JI, Mcdevitt HO. HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987;329(6140):599-604. doi:10.1038/329599a0.

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7. Freathy RM, Timpson NJ, Lawlor DA, et al. Common Variation in the FTO Gene Alters Diabetes-Related Metabolic Traits to the Extent Expected Given Its Effect on BMI. Diabetes. 2008;57(5):1419-1426. doi:10.2337/db07-1466.

8. Poulsen P, Grunnet LG, Pilgaard K, et al. Increased Risk of Type 2 Diabetes in Elderly Twins. Diabetes. 2009;58(6):1350-1355. doi:10.2337/db08-1714.

9. Shubrook JH, Chen W, Lim A. Evidence for the Prevention of Type 2 Diabetes Mellitus. The Journal of the American Osteopathic Association. 2018;118(11):730. doi:10.7556/jaoa.2018.158.