Genetics of Type 2 Diabetes

There are several factors that have to come together for a person to develop type 2 diabetes. While elements like nutrition and exercise have been shown to be important, it has also become clear that type 2 diabetes has a strong hereditary component.

If you have recently been diagnosed with type 2 diabetes, chances are that you’re not the first one in your family to live with the condition. For example, if one of your parents was diagnosed with diabetes before they were 50 years old, your risk of getting it is one in seven. It’s one in 13 if one of your parents became sick after age 50. If both your parents have diabetes, your risk is about one in two—in other words, there is a 50 percent chance you’ll develop type 2 diabetes sometime in your life.

You might be wondering why there still isn’t a cure, or at least a screening test to detect whether you will suffer from diabetes in the future, as there is for many other genetic diseases. Unfortunately, because type 2 diabetes is a “multi-factorial disease,” such a cure is not yet possible.

To understand the genetic component of type 2 diabetes, it is essential to understand where it fits in to the wide range of factors that contribute to the condition.

Genetic Mutation

Scientists have identified several small mutations in certain genes that have been linked to a higher diabetes risk. They are called single nucleotide polymorphisms (SNP), and even if one compares them with the already microscopically small DNA, they are tiny. They’re also very common, so not everyone who carries them will get diabetes—but many people who do have diabetes show one or more of these mutations.

Lifestyle & Family Inheritance

Lifestyle plays a huge role in developing, delaying, and preventing diabetes. Proper nutrition and regular exercise can significantly decrease your risk for diabetes. 

Lifestyle choices tend to run in the family: children learn from their parents, and if parents don’t lead active lives, the children are far more likely to adopt a sedentary lifestyle themselves.

Genetics & Weight

Genetics have been shown to play a big part in a person’s weight and their risk of becoming obese

This makes things very difficult for experts and scientists attempting to evaluate the importance of genetics on development of type 2 diabetes. For example, when looking at an overweight patient, they need to attempt to determine whether that patient became obese because of their genetics or their lifestyle. If they had lost weight, would that have prevented their diabetes or not? Would they be diabetic if they had the same lifestyle but none of the diabetes genes? These factors make it extremely complicated to come up with study designs that exclude all but one of those factors, and only study that one factor—for example, a certain gene.

Determining the Genetic Link

To begin with, scientists had to prove that there was a genetic link at all; that type 2 diabetes development isn’t just a matter of lifestyle. As families tend to have similar lifestyles, how could scientists determine whether genetics are involved at all? 

One sign that experts typically look for when attempting to isolate some genetic component to a disease is to investigate whether certain ethnic groups have a much higher incidence of developing that condition. For type 2 diabetes, one example is the Pima Indians. Members of that tribe have a high risk for obesity even with normal food intake. They have difficulties losing weight, and develop diabetes at a younger age than people of European descent. 

The TRP64ARG Mutation

The next step would be to try to isolate specific genetic mutations that occur in higher-risk populations. Geneticists studying diabetes found just such a gene mutation, which they called TRP64ARG. People who had two copies of this mutation, in particular, developed diabetes very early.

The strange name for this mutation actually tells a lot about the effects it can have. When you look at the mapped genome of the protein this gene sequence encodes, the normal protein would contain the amino acid tryptophan (TRP). In the mutated protein, the tryptophan is replaced by arginine (ARG). It is hard to imagine, but this tiny modification changes the function of the entire protein. This protein helps to burn fat when one is resting. In other words, people with the mutation have a much slower metabolism, which explains the symptoms mentioned above. 

This mutation is also more prevalent in people of Mexican and African descent, who have a higher risk for diabetes than Caucasians. 

Other Mutations

In the last few years, scientists have found more and more of these small mutations that might be linked to diabetes. In order to confirm the connection, researchers test a family with many diabetic members and attempt to map the entire genome of the family members with diabetes. These must then be studied over several generations. Sibling pairs are especially valuable in these studies, as they are exposed to the same environmental factors while growing up—if one of them contracts the disease and the other doesn’t, there is a higher chance that a genetic mutation is involved. Using these research methods, researchers have linked a few genes that are involved in glucose metabolization to an increased diabetes risk. It has also been shown that people carrying these mutations can avoid developing diabetes by adopting a healthy lifestyle.

Knowing all this, it’s easy to understand why there is no clear answer to why anyone develops diabetes. In light of the complicated genetics, there is only one safe thing to do: assume that you carry one or more of these mutations, and do everything you can to render it powerless by living an active, healthy life.