Type 2 diabetes (Spracklen, 2020) – Is Type 2 Diabetes Genetic?

person using glucose meter

Nebula Genomics DNA Report for Type 2 Diabetes

Is type 2 diabetes genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Is type 2 diabetes genetic? Sample report from Nebula Genomics
Is type 2 diabetes genetic? Sample variants from Nebula Genomics

Additional Information

What is type 2 diabetes? (Part 1 of Is type 2 diabetes genetic?)

Type 2 diabetes is a disorder in which insulin is present but cannot act properly. This is commonly known as insulin resistance. In the early years of the disease, the pancreas can compensate by producing high levels of insulin. At some point, however, the pancreas can no longer maintain the excessive insulin production. The amount of insulin produced is then no longer sufficient to control blood glucose levels, and type 2 diabetes mellitus manifests.

Cellular mechanism of type 2 diabetes
Type 2 diabetes occurs when the pancreas no longer makes enough insulin to control blood sugar levels. Wikipedia. CC-Attribution 3.0 Unported.

Type 2 diabetes usually develops in adults, although more and more children, teens, and young adults are being diagnosed. 

A type 2 diabetic produces much more endogenous insulin than the metabolically healthy person (hyperinsulinism), but due to high insulin resistance, blood glucose still rises; later, via a relative deficiency, absolute insulin deficiency occurs in some cases. The selfish-brain theory provides a possible explanation of the complex regulation of blood glucose and lipid metabolism by the hypothalamus, with the goal of always providing sufficient glucose to the brain.

Type 2 diabetes is often diagnosed late, not taken seriously, or inadequately treated, and physicians are sometimes uncertain about treatment. Patients, too, often tend to suppress it despite education and training, since noticeable health limitations often do not occur until acute, sometimes irreversible, damage manifests itself. 

Epidemiology (Part 2 of Is type 2 diabetes genetic?)

According to the Centers for Disease Control and Prevention (CDC), 34.2 million people (10.5% of the US population) had diabetes in 2020. 21.4% of those people are undiagnosed. They also estimate that 88 million people aged 18 years or older (34.5% of the adult US population) and 24.2 million people aged 65 years or older have prediabetes.

Causes (Part 3 of Is type 2 diabetes genetic?)

Two interrelated problems contribute to the onset of the disorder. They are that cells in muscle, fat, and liver become resistant to insulin and that the pancreas fails to supply enough insulin to control high blood sugar levels. A combination of genetics and lifestyle factors contribute to increased risk of developing the disease. 

Is type 2 diabetes genetic?

Children who have a single parent with type 2 diabetes have around 40 percent chance of developing the disease, while children who have two parents with the disorder have a higher risk of about 80 percent to also develop the disorder as adults. Studies have identified at least 150 DNA variations that are associated with the genetic risk of developing type 2 diabetes. A combination of these genetic mutations is most likely necessary for a change in risk to be present as opposed to a single variant. 

Mutations in any gene associated with mechanisms of controlling glucose levels and insulin processing have the risk of contributing to risk. These factors include genes associated with the development and function of beta cells in the pancreas, the release and processing of insulin, and cells’ sensitivity to the effects of insulin.

Some specific genes identified are:

  • TCF7L2, which affects insulin secretion and glucose production
  • ABCC8, which helps regulate insulin
  • CAPN10, which is associated with type 2 diabetes risk in Mexican-Americans
  • GLUT2, which helps move glucose into the pancreas
  • GCGR, a glucagon hormone involved in glucose regulation

Obesity

Being overweight or obese is considered one of the main causes of type 2 diabetes. In particular, excessive abdominal fat around internal organs such as the liver or pancreas, caused by a fat- and sugar-heavy diet, is considered a risk factor for those who develop diabetes. In addition to congenital insulin insensitivity, obesity results in additional insulin resistance of the insulin-dependent cells of the body. 

When such a cell is stimulated with insulin in healthy individuals, more type 4 glucose transport proteins (GLUT-4) are inserted into the cell membrane. In type 2 diabetics, this mechanism, among others, is disturbed. In their muscle and adipose tissue, GLUT-4 is downregulated. 

There is a correlation between the concentration of the messenger retinol binding protein 4 (RBP-4) and the extent of insulin resistance. RBP-4 is produced in excessive amounts in the adipose tissue of overweight individuals. This messenger appears to cause muscle and liver cells to respond poorly to the blood glucose-regulating hormone insulin. If insulin resistance improves after physical training, lower RBP-4 plasma levels can also be measured.

Other factors

Correlation studies have suggested that other factors are associated with increased risk of acquiring the disorder:

  • Fat distribution. Storing fat mainly in your abdomen — rather than your hips and thighs — indicates a greater risk. 
  • Inactivity. The less active you are, the greater your risk. Physical activity helps control your weight, uses up glucose as energy and makes your cells more sensitive to insulin
  • Blood lipid levels. An increased risk is associated with low levels of high-density lipoprotein (HDL) cholesterol and high levels of triglycerides.
  • People of certain races and ethnicities — including Black, Hispanic, Native American and Asian people, and Pacific Islanders — are more likely to develop type 2 diabetes 
  • Age. The risk of type 2 diabetes increases as you get older, especially after age 45.
  • A history of prediabetes or gestational diabetes (diabetes that developed during pregnancy)
  • Women with a condition called polycystic ovary syndrome

Symptoms of type 2 diabetes (Part 4 of Is type 2 diabetes genetic?)

Many people with type 2 diabetes may not realize it for several years as the symptoms occur gradually. Type 1 and type 2 diabetes have many symptoms in common. However, in contrast to type 1 diabetes, type 2 diabetes is rarely associated with weight loss and only with massively elevated blood glucose levels with increased urination and thirst. Early symptoms may include fatigue, weakness, visual disturbances, and tendency to infections (bacterial infections and fungal infections) such as frequent bladder infections.

According to Mayo Clinic, there are other symptoms of type 2 diabetes including:

  • Increased thirst
  • Frequent urination
  • Increased hunger
  • Unintended weight loss
  • Fatigue
  • Blurred vision
  • Slow-healing sores
  • Frequent infections
  • Numbness or tingling in the hands or feet
  • Areas of darkened skin, usually in the armpits and neck
Epidemiology and risk factors for type 2 diabetes
Type 2 diabetes and health information. The estimated number of Americans with diabetes has risen to 34.2 million. Credit: NHLBI. Flickr

Additionally, a rare symptom is hyperosmolar syndrome up to hyperosmolar coma can occur. This symptom appears when an extremely high blood glucose level causes the kidneys to excrete so much water that the loss of fluid can no longer be compensated for by drinking.

Comorbid disease

Potential complications arise in patients with type 2 diabetes, some of them serious. Diabetes is associated with an increased risk of heart disease, stroke, high blood pressure and narrowing of blood vessels (atherosclerosis) as well as nerve damage (neuropathy) in limbs and other nerve damage. Nerve damage in the digestive system can cause problems with nausea, vomiting, diarrhea or constipation. For men, nerve damage may cause erectile dysfunction.

Diabetics may experience kidney disease, eye damage such as cataracts and glaucoma, skin conditions including bacterial and fungal infections, slow healing, hearing impairment, sleep apnea, Alzheimer’s disease and other disorders that cause dementia. 

Diagnosis (Part 5 of Is type 2 diabetes genetic?)

Most diabetes testing focuses on A1C measurements. A1C is measured through a blood test and informs doctors and patients of their average blood sugar level over two to three months. This measurement is useful not only in diagnosing the disease, but also in monitoring it. A1C levels below 5.7% are considered normal, between 5.7%-6.5% are prediabetic levels, and anything over 6.5% indicates diabetes range. 

Other tests used to assess blood sugar levels include the fasting plasma glucose test, which tests the amount of glucose in plasma or the oral glucose tolerance test which measures how your body responds to added glucose.

Some at-home testing kits may help diagnose the condition through easy to use measurements. Day Two is a gut microbiome test designed to help patients with Type 2 diabetes target their diet. Some lab testing companies like LetsGetChecked and Everlywell offer a finger prick test that measures A1C and other contributing factors, which can be done from your home without going to a doctor’s office. You can also sequence your entire genome to see if you have a combination of the genetic predispositions through whole genome sequencing companies like Nebula Genomics!

Prevention (Part 6 of Is type 2 diabetes genetic?)

Diet, exercise, and losing weight are the key ways to delay or prevent the disease. You can proactively help to prevent type 2 diabetes, even if you have a family history of the disease. These prevention strategies are based on modified healthy lifestyle factors that help keep weight and blood sugar under control. Eating healthy foods that are low in fat and calories and high in fiber is one of the most important factors. Staying active and losing excess body weight are also  incredibly effective prevention strategies.

A recommended diet for people with diabetes. Pixy.
A recommended diet for people with diabetes. Pixy.

Treatment (Part 7 of Is type 2 diabetes genetic?)

In type 2 diabetes, increased insulin resistance can be reduced by healthy eating, weight loss, and increased exercise. The first options for managing diabetes usually include lifestyle changes that help the patient maintain a healthy body weight. Many of these diabetes treatments are the same lifestyle factors as prevention, including eating foods high in fiber, increased aerobic activity, and eating in regular intervals. 

In most cases, lifestyle changes are enough to treat type 2 diabetes. Regular self-monitoring of blood glucose levels using different types of diabetic monitoring systems is an important part to most diabetes care. 

A glucose monitor for those with type 2 diabetes
A finger prick glucose monitor. Wikipedia. CC-Attribution 2.0 Generic.

However, if the pancreas is not making enough insulin, doctors will instruct patients to take insulin therapy, which involves insulin injections once to several times a day and/or other prescription medications. 

Healthline describes some of the most common diabetes medicines:

  • Metformin lowers blood glucose levels and improves how your body responds to insulin 
  • Sulfonylureas (oral medications) help your body make more insulin
  • Meglitinides quickly stimulate your pancreas to release more insulin
  • Thiazolidinediones make your body more sensitive to insulin
  • Dipeptidyl peptidase-4 inhibitors are milder medications that help reduce blood glucose levels
  • Glucagon-like peptide-1 (GLP-1) receptor agonists slow digestion and improve blood glucose levels
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors help prevent the kidneys from reabsorbing glucose into the blood and sending it out in urine

Since type 2 diabetes is often associated with high blood pressure as part of the metabolic syndrome, and high blood pressure further accelerates late complications, especially in the eyes, kidneys, and large blood vessels, high blood pressure must be detected and treated early. 

Especially with regard to macrovascular risks such as myocardial infarction or stroke, optimal blood pressure control is even more important than optimizing sugar metabolism. However, for the microvascular risks of the eyes and nerves, optimization of blood glucose is considered more important.

More resources and support are available from the American Diabetes Association or the National Institute of Diabetes and Digestive and Kidney Diseases, a part of the National Institutes of Health. This resource is especially useful to learn about the risk of diabetes and digestive and kidney diseases as well as the symptoms of diabetes and digestive and kidney diseases. You can also find some interesting information on reversing diabetes here.

You can find more diabetes reports on our website. If you liked this article, you should check out our other posts in the Nebula Research Library!