Does Diabetes Always Have a Genetic Cause?

Before choosing the right kind of treatment for diabetes, experts need to discover the main issues that have led to it.

 Although Diabetes is a common disorder among people, factors like genetics, diet, lifestyle, and environment have been identified as the main reasons so far. It's important to note that the role genetics plays is highly depends on the type of Diabetes. World Diabetes Day is for raising awareness about this disorder, its causes, and encouraging regular check-ups. As nowadays, there is much research about the origins of this problem and its different types; in the following, we will explain how genetics might have an impact on each type of this disease.


Type 1 Diabetes

 This type of Diabetes happens when the immune system strikes and demolishes insulin. Insulin is a hormone that helps carry glucose into your cells to be used for energy. It is made by the cells in the pancreas. It can result in hyperglycemia when the level of glucose in the blood is too high. 

 Individuals who have type 1 diabetes must take injections to make up the insulin their body doesn't produce. Their blood glucose levels should be monitored daily.

 Despite the fact that this form of Diabetes can occur at any age, it typically appears in early adulthood or childhood (previously known as juvenile Diabetes). Autoantibodies that attack the insulin-producing beta cells might be in the blood for years before a diagnosis is made. 

 Yet, the existence of these autoantibodies does not necessarily lead to such disorders in a person. "We know some of the autoantibodies involved in attacking the pancreas. We can screen for them, but there are patients who have positive autoantibodies and never develop type 1 diabetes," explains Joshua D. Miller, MD, the medical director of diabetes care at Stony Brook Medicine in Stony Brook, New York.

 Studies show that among all races, white people have higher rates of type 1 diabetes than other racial and ethnic groups in the United States. Additionally, type 1 diabetes is more likely to occur in the winter. It is mostly triggered by viral infections, such as German measles, mumps, and Coxsackievirus, which are related to the wintertime. Moreover, researches have depicted a link between being breastfed as a baby and having a lower risk of type 1 diabetes. 

 Therefore, individuals with type 1 diabetes (Autoimmune disorder) are at a higher risk of having other autoimmune diseases, such as celiac disease, Hashimoto's thyroiditis, pernicious anemia, and Graves' disease. 

 The last point to mention is that while people with a family history of type 1 diabetes might be predisposed for developing it, in most cases, the inheritance pattern is unclear.


Type 2 Diabetes

 When your body doesn't use insulin correctly, type 2 diabetes occurs (insulin resistance). At first, the pancreas makes more insulin for compensation, but in time, it isn't enough to maintain blood glucose at normal levels. Between 90% and 95% of individuals have type 2 diabetes, which typically develops in people who are older than 45.

 Being obese or overweight is also the leading risk factor for type 2 diabetes. If your body mass index (BMI) is 25 or higher, you are at risk for type 2 diabetes. For Asian Americans and Pacific Islanders, the high-risk BMI are 23 and higher and 26 or higher in turn.


 Researches show that African Americans, American Indians, Alaska Natives, Hispanics/Latinos, Asian Americans, Pacific Islanders, or Native Hawaiians are at higher risk for type 2 diabetes even if they are not overweight. 


 Cardiovascular health conditions, like having a high level of triglycerides in your blood, high blood pressure, a low level of HDL cholesterol, or a history of heart stroke or disease, are also related to type 2 diabetes. 


 "The impact of family history on developing Diabetes is better established with type 2 than type 1. If you look at people who have type 2 diabetes, they are more likely to have people in their family that also deal with Diabetes, obesity, or other risk factors. However, it's hard to know if that influence is due to genes alone or a shared lifestyle and environment. It could also be that what they are sharing is not a genetic variation. Maybe they are sharing their diet or a lack of access to opportunities for exercise, depending on where they live. The genetic test is only going to reveal an association or a probability that someone might get type 1 or type 2 diabetes because the disease is not only caused by genetic variation," says Mónica Alvarado, a certified and licensed genetic counselor and the regional administrator for Genetic Services at Kaiser Permanente in Pasadena, California.


Gestational Diabetes

 Pregnant women usually develop a certain amount of insulin resistance to ensure that there's enough glucose available for providing energy for the growth of the fetus. Most pregnant females do not go on to develop gestational Diabetes, although some do. A combination of genes, lifestyle factors, and the environment are likely to cause type 2 diabetes. Many females who develop the condition have at least one close family member, such as a sibling or parent, who has had type 2 diabetes or gestational Diabetes.


 Insulin resistance in gestational Diabetes may lead to preeclampsia (high blood pressure during pregnancy) and premature birth. Babies born of mothers with this condition tend to have higher than healthy birth weights, which can create complications during delivery. The infants of a female with Gestational Diabetes are more likely to develop low blood sugar levels soon after birth, which is so dangerous. The offspring has a high risk of developing obesity, type 2 diabetes, and heart disease later in life. 

 The chance of gestational Diabetes is on the rise, affecting up to 14% of all pregnancies in the U.S. Increasing maternal age may be a factor. In addition to that, half of all females with Gestational Diabetes will go on to develop type 2 diabetes.


Is Genetic Testing beneficial for Diabetes? 

 The genetic mutations that cause Diabetes involve the ability of the body to use insulin or the proteins responsible for insulin production. Mutations cause the proteins to malfunction. These kinds of tests can identify these mutations in certain cases, but the usefulness of the provided information varies. It actually depends on the form of Diabetes (monogenic or polygenic).


Monogenic Diabetes

 In 1% to 4% of all diabetes cases, the condition results from mutations in a single gene (monogenic): that means you can test and pinpoint for a single gene.

 Two of the most usual monogenic forms of Diabetes are maturity-onset Diabetes of the young (MODY), which typically appears during young adulthood or the teen years, and neonatal diabetes mellitus (NDM), which is most common in infants and newborn babies.


Maturity-Onset Diabetes of the Young (MODY)

 Some forms of MODY result in high levels of blood sugar that stay stable throughout life, resulting in no complications and no symptoms (or mild symptoms). Other forms might need treatment with a class of oral medications (sulfonylureas), which increases the release of insulin from beta cells.

 "There are at least ten genes that have been related to forms of MODY," says Scott Weissman, a certified genetic counselor on the faculty of Northwestern Medicine's Center for Genetic Medicine in Chicago and the founder of Chicago Genetic Consultants, LLC, in Northbrook, Illinois. The most common mutations are found in the GCK gene or the HNF1A gene.

 Weissman cites that GCK mutations, which he believes are responsible for 30 to 60% of MODY cases, are an answer for why genetic testing can be useful. "Although the individual's blood work looks like they have type 1 diabetes, with this type of mutation they actually don't need insulin because it doesn't make a difference in the treatment of the disorder". Testing will tell the doctor that there is no need to take insulin, avoiding unnecessary treatments. Moreover, their relatives can be tested for the gene and monitored for the development of MODY.


Neonatal Diabetes Mellitus (NDM)

 In general, NDM affects up to 1 in 400,000 infants during the first 6 to 12 months of life. The condition is frequently mistaken for type 1 diabetes because Infants with NDM do not produce enough insulin. They are born undersize and tend to grow less rapidly than their peers without NDM. For half of the babies with NDM, the condition is permanent, while for the other half, it might disappear but can reappear later.

Most forms of MODY and NDM are caused by autosomal dominant mutations (when only one parent carries the gene for the disease, they can be passed on to children). In these cases, the parent who carries the gene has a 50% chance of having an affected child.


Polygenic Diabetes

 Most kinds of type 1, type 2, and gestational Diabetes are polygenic. It means they involve multiple genes and lifestyle and/or a complex interaction with the environmental factors.

 "The usefulness of the genetic test in polygenic Diabetes is restricted because the disease is not only caused by genetic variation. In addition, it won't indicate with certainty if someone will or won't go on to develop the disease," says Alvarado. 



 In fact, traditional diagnostic testing, such as looking at hemoglobin A1C (a measure of blood glucose), are typically more helpful to find out about the type of Diabetes one has compared to genetic testing.

 In a study published by Diabetes Care in July 2018, experts looked at the relatives of individuals with type 1 diabetes who did not have the disease themselves but did have one or more positive autoantibodies. It was found that a higher genetic risk score helped to predict their progression to develop type 1 diabetes. 


 Long story short, even without genetic testing, it is wise to pay heed to your family history and risk parameters for Diabetes since sometimes a combination of factors may contribute to it.