Genetic Tests & Diabetes

Summary

Genetic tests are laboratory tests used to detect potential problems in a person’s genes that may show a risk for or the presence of certain medical conditions.

Scientists are working on genetic testing for diabetes. It has already been developed for some forms of diabetes, diabetic complications and risk factors, including:

Maturity-onset diabetes of the young (MODY)
Some variations of diabetes in infants
Wolfram syndrome
Diabetic heart disease
Diabetic retinopathy and glaucoma
Several forms of insulin resistance
Cystic fibrosis
Celiac disease (gluten intolerance)
Hereditary pancreatitis
Hemochromatosis (“bronze diabetes”)

It is important to note that most genetic tests can show only an increased risk for a disease and with rare exceptions do not indicate that it will develop. Genetic counseling is advised for people considering or undergoing such tests to help them understand the implications.

Many genetic tests are blood tests. Others are based on samples of urine, cells from inside the cheek, skin cells, hair, bone marrow, or the amniotic fluid or placenta tissue of pregnant women.

Some of the tests can be analyzed at a general medical laboratory, but others must be sent to a specialized genetics lab. There are also kits available for use at home, but their reliability is unknown, and the U.S. Food and Drug Administration does not recommend them.

About genetic tests

Genetic tests examine genetic material for abnormalities that may indicate a person’s risk for developing a disease. This material may be one or more of the following:

Genes. The basic unit of hereditary. The human body has about 20,000 to 25,000.
Chromosomes. Strands in the nucleus (center) of a cell that contain genes.
DNA (deoxyribonucleic acid). A substance in genes that contains the blueprint for the body’s growth.
RNA (ribonucleic acid). A nucleic acid that controls protein synthesis in cells.
Proteins and certain metabolites (products of metabolism, such as amino acids).

Most newborns in the United States undergo routine genetic testing for conditions such as sickle cell anemia, cystic fibrosis, congenital hypothyroidism, congenital adrenal hyperplasia and enzyme deficiencies (e.g., phenyiketonuria). Other cases in which genetic testing is used include screening people who have inherited risks for certain forms of cancer, such as patients with familial adenomatous polyposis, who are prone to developing colon cancer. With diabetes, genetic testing is still in its early stages.

Diabetes is a complex disorder, with most forms caused by multiple factors, often including genetics, environment and behavior. It is more difficult for scientists to develop genetic tests for type 1 diabetes, type 2 diabetes and other multifactorial diseases than for monogenic diseases caused by one defective gene, such as cystic fibrosis, maturity-onset diabetes of the young or Wolfram syndrome.

Research indicates that most cases of type 2 diabetes involve more than one gene, and the gene combinations may differ between families. In addition, the genes associated with diabetes may have only slight variations from unaffected genes, and it is possible that the variations are common in the human population. These factors make interpreting the results of genetic research on type 2 diabetes difficult, though scientists have linked several genes to increased risk, including a gene variant called TCF7L2 that could predispose more than a third of Northern Europeans and many black Americans to type 2 diabetes.

Most people with type 1 diabetes have variations of a gene called HLA, but other factors such as viruses are also believed to play a role in development of this autoimmune disease.

Genetic tests are already available for several disorders related to diabetes. These may benefit individuals who:

Have a relative with the disease
Show signs of the disease
Are concerned about passing a hereditary disease to children
Want pregnancy testing

Genetic disorders can be recessive, meaning an individual must inherit the gene from both parents, or dominant, meaning a disease passed down from one parent. Furthermore, genetic disorders can be autosomal, meaning they affect females and males equally, or can involve the X or Y sex chromosomes (the egg contributes an X, the sperm an X or Y; a female embryo is XX, a male XY). MODY is an example of an autosomal dominant disease. Wolfram syndrome is an autosomal recessive disease.

Genetic testing and gene therapy were significantly advanced in 2003 when scientists with the Human Genome Project mapped the human genome (all human DNA). That year there were about 400 genetic tests available in the United States. This number has topped 1,000 and is growing.

Genetic tests usually cost from several hundred dollars to several thousand dollars. Some insurance plans may cover them if the tests are necessary and are prescribed by a physician.

A growing number of Internet companies offer home kits for genetic testing. These often involve a swabbing of the inside of the cheek to collect cells rather than a blood test. After the consumer sends the sample back to the company, the results can be made available online.

However, the U.S. Food and Drug Administration has not evaluated the reliability of home genetic tests. It is possible that the sample could become contaminated and generate inaccurate results. In addition, significant privacy issues are associated with sensitive medical information being available on the Internet. Concerns include employment discrimination and refusal by insurance companies to cover costs of a medical condition. Also, genetic tests need to be interpreted by specialists, and people who have undergone testing benefit from genetic counseling to understand the results.

Genetic tests and diabetic conditions

Scientists are trying to develop genetic tests for type 1 diabetes, type 2 diabetes and other forms of the disease. Researchers have already developed genetic blood tests for several diabetic conditions:

Maturity-onset diabetes of the young (MODY). An uncommon form of diabetes caused by a genetic defect inherited from either parent. Genetic testing involves examining a blood sample to determine if the patient’s DNA contains a genetic mutation consistent with MODY, especially if it is the same mutation found in a diagnosed relative. Scientists have so far identified eight variations of MODY, each one linked to a different gene mutation.

Children of parents with MODY are most often diagnosed through genetic testing before symptoms occur. Early intervention can help physicians offer guidance to manage the disease, delay its onset or possibly prevent it. With a positive result, periodic glucose tests are highly recommended to screen for diabetes.

Wolfram syndrome. A rare genetic disorder that destroys the nervous system and causes insulin-dependent diabetes, blindness, hearing loss, diabetes insipidus and other problems. Genetic testing can confirm the presence of Wolfram syndrome’s usual cause: mutations to a gene called WFS1.
Rare forms of diabetes diagnosed in newborns. Some cases of neonatal diabetes that involve defects in certain genes (ABCC8 or Kir6.2) can be treated with sulfonylureas rather than insulin, scientists have recently found. These researchers have recommended that people who were diagnosed with diabetes before 6 months of age undergo genetic testing to see if their condition might respond to treatment with oral medication rather than a lifetime of injections.
Maternally inherited diabetes mellitus and deafness (MIDD). An uncommon form of diabetes that involves deafness and impaired secretion of insulin. MIDD involves a mutation in an RNA gene that is transmitted from the mother.
Some conditions involving insulin resistance. Several diabetic disorders involve defects in the insulin receptor gene:
- Type A insulin resistance. A condition in which the body’s cells lose their ability to use insulin. Insulin resistance and hyperinsulinemia may cause a skin condition called acanthosis nigricans and can cause an increase in the level of male hormones in girls, leading to polycystic ovarian syndrome.
- Lipoatrophic diabetes. A disorder, sometimes considered a variation of type 2 diabetes, that is marked by a lack of body fat.
- Leprechaunism (also called Donohue syndrome). A rare, fatal form of mental and physical retardation present at birth that often causes death within the first year of life.
- Rabson-Mendenhall syndrome. Another rare congenital disorder involving severe insulin resistance and a poor prognosis.

Scientists are also using genetic tests with several diabetic complications and risk factors:

Heart disease. The primary cause of death in people with diabetes. Researchers have found three forms of a blood protein called haptoglobin, variously linked to a high, intermediate or lower risk of heart disease in diabetic patients.
Diabetic retinopathy. A leading cause of blindness, caused by damage to tiny blood vessels in the back of the eye. DNA tests that reveal a variant of a protein called vascular endothelial growth factor (VEGF) indicate a higher risk of the disease.
Glaucoma. Another leading cause of blindness, involving damage to the optic nerves. A genetic test has been developed to detect mutations of a gene called TIGR that have been linked to increased risk of developing this eye disease, which is more common in people with diabetes than in nondiabetics.
Hemochromatosis (also called bronze diabetes). A condition in which the body absorbs and stores too much iron. Excess iron can damage the pancreas, heart, liver and other organs and tissues. Such damage to the pancreas can lead to secondary diabetes. Most cases of hemochromatosis are a hereditary condition affecting people of Northern European ancestry. The gene connected to the condition is called HFE. Hemochromatosis is more common than most genetic diseases and often goes undiagnosed. Genetic testing may be recommended to determine if a patient has the HFE gene mutation.
Celiac disease. A digestive disease in which the body cannot tolerate gluten, a protein found in wheat, rye, barley and other grains. Celiac disease, the most common genetic disease in Europe, is linked to increased risk of type 1 diabetes and other autoimmune diseases. Americans are not routinely screened for it, but family members of people who have been diagnosed may need to be tested for antibodies, according to the U.S. National Institutes of Health. About 10 percent of an affected person's parents, siblings or children will also have the disease. The longer a person with the disease goes undiagnosed and untreated, the higher the risk of malnutrition and other complications. Symptoms include abdominal pain, chronic diarrhea and unexplained weight loss as well as decreased bone density.
Cystic fibrosis. A disease in which the body produces thick mucus that affects the lungs, pancreas and other organs. Diabetes is a common complication. Genetic screening of newborns for cystic fibrosis is common in the United States.
Hereditary pancreatitis. A rare genetic condition characterized by repeated episodes of acute inflammation of the pancreas. A special blood test can show mutations in the cationic trypsinogen gene. The majority of people with these mutations develop hereditary pancreatitis. The remaining people with the mutation can still pass the gene to their children. Pancreatitis, most cases of which are nonhereditary, is a risk factor for secondary diabetes.

Types and differences of genetic tests

Many genetic tests involve collecting a sample for a blood test. Other methods of collection may involve:

Inner cheek cells, skin cells or hair
Urine tests
Bone marrow
Prenatal sampling of amniotic fluid or placental tissue

There are three types of genetic tests:

Biochemical testing. Used when the physician suspects a disorder caused by a certain biochemical marker, such as an enzyme or other protein. Biochemical genetic tests usually involve samples of blood or urine that can be done in a general medical laboratory.
DNA testing. Used when the physician suspects a single-gene (monogenic) condition such as hemophilia (a blood clotting disorder) or Wolfram syndrome. The genetics lab compares the sample to known mutations of the specific gene. DNA tests may be performed on blood, skin scrapings or hair samples.
Chromosome analysis (also called cytogenic testing). Used when the physician suspects specific chromosomal abnormalities such as Down syndrome. The genetics lab examines the sample for structure, arrangement and any chromosomal defects. The sample may be from bone marrow, blood, skin, amniotic fluid or placental tissue.

Genetic tests can also be categorized according to purpose:

Genetic screening. Performed to test a population group in order to identify a subgroup at high risk of having or transmitting a genetic condition.
Carrier screening. Tests used in family planning to determine whether an unaffected individual carries a certain gene. Recessive-gene diseases such as Wolfram syndrome cannot appear in a child unless each biological parent has the gene. Dominant-gene diseases, such as maturity-onset diabetes of the young, can appear in a child if only one parent has the gene. These tests help determine whether a person could transmit the condition to any future biological children.
Predictive genetic testing. Testing of an individual who does not have signs of a disease but might inherit it from a biological parent.
Presymptomatic genetic testing. Tests that show an individual will develop a disease. This type of test is available for only a few genetic disorders, such as Huntington’s disease (a nervous system disease).
Diagnostic genetic testing. Tests that help confirm or help rule out diagnosis of an inherited disease in individuals who have signs of the disease.
Prenatal genetic testing. Testing of a fetus during pregnancy, or of fertilized eggs before uterine implantation, to reveal a mutation (abnormality) showing presence or risk of a disease.

Factors that may affect genetic test results

Many factors can influence results of genetic tests. For example, tests requiring blood samples can be affected by medications, supplements, use of alcohol, failure to fast as directed before the test, or recent illness. Those involving urine samples can be affected by overexertion, medication, vitamins and drinking too much or too little fluids.

Patients undergoing analysis of DNA or chromosomes may be advised to avoid a blood transfusion for a certain period before genetic testing.

Genetic tests are harder to perform and interpret than most other medical tests. Genetic blood and urine tests often can be done at general laboratories. DNA and chromosome tests may have to be performed at specially licensed labs.

Physicians and public health authorities have concerns about the accuracy of some genetic assessments and the lack of governmental regulation and standardization of laboratories and testing methods.

Understanding genetic test results

A positive result in a genetic test indicates the presence of a particular gene or a gene mutation. Presence of such a gene or mutation usually means only that the patient has increased risk of a disease, not a certainty of getting the disease. Additionally, a positive result does not indicate the potential severity of symptoms for a person with the disease.

The point about increased risk is crucial. Most genetic tests merely show a predisposition to a disease that might never develop or might not strike until late in life. In only a few monogenic (one-gene) disorders, such as Huntington’s disease, can genetic tests show a person will develop the disease.

In some cases other testing will reveal more information. For example, prospective parents can take a blood test to show whether they carry the gene mutation for cystic fibrosis. If both are carriers, this means there is a 25 percent chance their child will have the disease. Prenatal testing (amniocentesis or chorionic villus sampling) can then reveal if the fetus has cystic fibrosis. Or, after birth, a test involving a sweat sample can reveal if the infant has the disease.

Geneticists worry that the growing availability of genetic tests will cause confusion in the general public about the meaning of results. They recommend that people undergoing such tests get expert advice from genetic counselors before seeking testing and afterward.

In addition, negative test results for conditions involving multiple genetic factors, such as type 2 diabetes, can be inconclusive or “non-informative.” These disorders may involve genes and mutations that the test does not cover or that are not yet be known to science. Multifactorial diseases also often involve complex environmental and behavioral triggers, such as diet, lack of exercise, exposure to toxins or exposure to viruses. Even with a genetic disorder such as maturity-onset diabetes of the young (MODY), scientists have only recently found the genetic defects linked to two previously unknown forms of the disease, and they believe there are still several more undiscovered gene mutations that can cause MODY.

It is also important to realize that a person with no evidence of a disease through genetic testing could in some cases still get the disease. For example, someone who tests negative for hereditary pancreatitis might later develop the more common nonhereditary type.

Frequency of genetic testing

Tests of DNA and chromosomes do not need to be repeated. People are born with a lifetime of genes. Biochemical tests can vary and might need to be repeated for confirmation.

Of course, if prenatal genetics tests are used, results apply only to the fetus being tested and would have to be repeated for additional pregnancies, if desired.

Genetic tests may indicate the need for regular testing of other types. For instance, if test results are positive for maturity-onset diabetes of the young (MODY), periodic glucose tests are advised.

Advantages and disadvantages of genetic tests

Genetic tests have benefits and risks. They can provide useful information, but some people who undergo them are not prepared for the implications. The results may be ambiguous and lead to unnecessary stress. Experts recommend undergoing genetic counseling to decide whether to proceed with genetic testing and to help understand the results.

Potential advantages of genetic tests include:

Getting potential help in diagnosing a condition
Identifying family members who may be or are at risk of developing a disease
Screening newborns so disorders might be treated earlier
Improving habits such as exercise and diet to reduce risk of a disorder
Making a decision about whether to have children
Reducing uncertainty and worry about risk of a disease
Helping physicians choose and predict response to treatments
Helping scientists develop diagnostic tools and treatments
Aiding in identity testing and criminal forensics

Possible disadvantages of genetic testing include:

Receiving false positives that inaccurately show a gene or mutation
Receiving false negatives that fail to show a gene or mutation
Assuming that risk of a disease means the disease will occur
Assuming that a negative result means a disease could never occur
Facing discrimination by employers, insurers, governments or others
Basing family-planning decisions on results that may be uncertain
Experiencing depression and fear over test results, especially for unpreventable or untreatable disorders

In addition, there are the usual minor, uncommon risks for genetic tests that involve blood samples (e.g., infection). Risks of bone marrow tests used in some genetic testing include bleeding, infection and, in rare cases, puncture of organs, blood vessels or other internal structures. Risks of amniocentesis and placenta testing (chorionic villus sampling) include spontaneous abortion or premature labor, injury to the fetus, maternal bleeding and infection.

Questions for your doctor about genetic tests

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about genetic testing:

What exactly do genetic tests reveal? Can they predict diabetes?
What conditions related to diabetes can be detected with genetic tests?
Do you recommend that I get genetic testing?
Where do you recommend that I have a genetic test?
What can I expect during the test?
How and when will results be explained to me? Will I have genetic counseling?
Are home testing kits useful, or do you recommend that I avoid them?
What are the risks and benefits of genetic tests for me?
If I get a positive test result, what does that mean? What does a negative result mean?
How accurate are genetic tests for my condition?
My partner and I are thinking about having a baby. Will genetic tests tell us whether our child would develop diabetes or other diseases? Do you recommend prenatal genetic testing for us?
What genetic screening tests should our newborn have?