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Genetics &
Diabetes
Genetics may play a role in the development of
diabetes for many patients, along with environment
and behavior. Scientists have linked several
specific genes to the various forms of diabetes.
The risks of developing type 1
diabetes, an autoimmune disease, are greater when a
parent also has the disease. This factor indicates a
probable genetic factor. A single gene that is
responsible for type 1 diabetes has not been
identified. However, 19 sections of the human genome
(complete genetic material) are believed to be
involved.
Type 2 diabetes is also highly
complex developmentally. It is the most common type
of the disease and has the clearest association with
genetic inheritance. It may involve multiple genes
that cause insulin resistance or that result in loss
of insulin being produced by the pancreas.
Researchers have found that exercise and weight loss
may often prevent type 2 diabetes in people with
genetic risk factors.
For other types of diabetes, such
as maturity-onset diabetes of the young (MODY), a
genetic link is clearly established. There are six
types of MODY, each associated with a single genetic
defect inherited from a parent. Other diabetic
conditions with identified genetic causes include
Wolfram syndrome, type A insulin resistance and
Rabson-Mendenhall syndrome, which also causes
insulin resistance.
About
Genetics
It is easier to understand genetics and the link to
diabetes by learning some of the basic terms used to
study the inheritance of biological characteristics.
These include:
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Chromosomes.
Rod-shaped
element in the nucleus (center) of each cell.
Chromosomes contain the hereditary information
that guides all cell actions. A person typically
has 46 chromosomes, and one set of 23 chromosomes
is inherited from each parent. The sex-determining
chromosomes X and Y are two of the 46 chromosomes.
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Genes.
The basic unit of hereditary. Each gene is located
in a specific site on a chromosome. Each human
cell has about 20,000 to 25,000 genes. A person
inherits two copies of each gene, one from each
parent. They help determine physical
characteristics such as eye color and skin color.
Genes also contribute to other characteristics in
which environment and behavior play a role, such
as body weight, intelligence and the risk of
diabetes and other diseases. How genes are
involved in diabetes is not clearly understood.
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Genome.
All of the genetic material in an organism’s
chromosomes.
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DNA (deoxyribonucleic acid). A complex
substance in genes that contains genetic information
needed to make the body’s proteins. These proteins
allow the body to function and grow.
Genetics
and Type 1 Diabetes
Type 1 diabetes is an autoimmune disease, in which
the immune system destroys the body’s capacity to
produce insulin. Insulin is a hormone that helps
cells use glucose (blood sugar) for energy.
Researchers have found many factors that appear to
be linked to type 1 diabetes, but there does not
seem to be any single cause. Some of the factors
include viruses, certain diets, chemicals and other
environmental factors. Genetics is also believed to
play a role, which is indicated by the disease
occurring multiple times in a family.
A
family history of type 1 diabetes is a major
indicator that a person may also develop the
disorder. The risk of a child developing type 1
diabetes in association with a parent with the
disease is the following:
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1 in 17 when the
father has diabetes
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1 in 25 when the
mother has diabetes and gave birth to the child
before age 25
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1 in 100 when
the mother has diabetes and gave birth to the
child after age 25
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1 in 4 to 1 in
10 when both parents have diabetes
For each of these figures, the risk of diabetes
doubles if the parent developed the disease before
age 11.
The high rate of occurrence of diabetes within
families helped encourage research into genetic
links to the disease. Scientists are trying to
determine which genes are involved in individuals
with type 1 diabetes and how genetic mutations
interfere with the production of insulin. To date,
they have not found a single gene responsible for
type 1 diabetes. However, there are about 19
sections of the human genome that appear to be
related to a susceptibility to type 1 diabetes.
One section of the genome contains several genes
involved in building human leukocyte antigens (HLA).
The proteins formed by these genes help the immune
system recognize the body’s own cells. When HLA
genes malfunction, an autoimmune disorder may occur.
There are many types (alleles) of HLA genes.
According to the American Diabetes Association, 95
percent of people with type 1 diabetes have HLA-DR3,
HLA-DR4 or both alleles. The HLA genes involved in
diabetes also vary by ethnicity and race. HLA-DR3
and HLA-DR4 are most common in white diabetic
patients, but HLA-DR7 is common in patients of
African descent and HLA-DR9 is common in patients of
Japanese descent.
The inherited HLA-DR gene makes individuals more
susceptible to type 1 diabetes, but it is not the
only factor. Other genes, including other HLA genes
(HLA-DQ) and IDDM2 (the insulin gene), are also
likely to be involved. Researchers are continuing to
study additional gene clusters and chromosomes to
determine their role in type 1 diabetes.
The genetic factor is a complicated issue in the
development of type 1 diabetes. Most people with the
disease do not have a parent or sibling with it.
Also, identical twins have identical genes, but
there is only a 50 percent chance of both twins
developing the disease. This means that factors in
addition to genetics play a role in the development
of the disease.
A
form of type 1 diabetes that can develop in adults
is known as latent autoimmune diabetes of adulthood
(LADA). It is not known how the genetic risk factors
for LADA may differ from those of standard type 1
diabetes.
Genetics and
Type 2 Diabetes
Type 2 diabetes is a condition in which the body
resists the insulin produced by the pancreas and may
fail to make enough insulin to maintain normal
glucose (blood sugar) levels. It is by far the most
common form of diabetes.
A
genetic link to type 2 diabetes appears much
stronger than for type 1. Identical twins share the
same genetic code, but should one identical twin
develop type 2 diabetes, the risk for the other twin
is 60 to 75 percent, according to the American
Diabetes Association.
Evidence for the genetic basis of the disease is
also provided by its frequency among racial and
ethnic groups. In the United States, type 2 diabetes
occurs most frequently among African Americans,
Hispanics/Latinos, Native Americans, Alaska Natives,
Asian Americans and Pacific Islanders.
Some researchers believe that this prevalence is due
to the presence of a “thrifty” gene or set of genes
inherited amongst these ethnic groups. In theory,
the thrifty gene originally altered the use of
insulin to enable people to store energy in the body
more efficiently to survive periods of food
scarcity. Surviving food scarcity periods is
generally no longer an issue in modern Western
societies, and the thrifty gene has shifted from
being a survival mechanism to being a risk factor
for diabetes.
Research indicates that in most cases of type 2
diabetes there is more than one gene involved and
that the gene combinations may differ between
families. In addition, the genes may have only
slight variations, and it is possible that the
variations are common in the human population. These
factors make research into the genetics of type 2
diabetes difficult.
These genes appear to affect the way insulin acts on
tissues, creating insulin resistance. This condition
impairs the ability of cells to use the insulin that
is present, and it accumulates in the bloodstream,
causing hyperinsulinemia. In addition, other genes
may affect the insulin-making beta cells of the
pancreas, limiting their ability to produce enough
insulin to overcome the resistance.
Scientists in recent years have linked several genes
to development of type 2 diabetes. For example:
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A gene variant
called TCF7L2 could predispose close to 38 percent
of Northern European populations and many black
Americans to type 2 diabetes. It might increase
their risk of diabetes by 80 percent. However,
these researchers found that moderate exercise and
weight loss the same preventive treatments
touted in the landmark Diabetes Prevention Program
could virtually erase the additional risk in
people with this genetic makeup.
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A gene called ARNT
(aryl hydrocarbon receptor nuclear translocator)
has been found to be expressed abnormally in the
beta cells of people with type 2 diabetes. The
discovery provides new insight into the
development of the disease, and potentially a
treatment.
The identification of some genes involved in type 2
diabetes has led to the development of genetic tests
for the disease. These tests examine samples of
blood or cells from the inside of the cheek for the
responsible gene. Interpreting the results is
complicated, and genetic counseling is recommended
to patients interested in undergoing genetic
screening.
Genetics can also contribute to factors that may
lead to type 2 diabetes. Obesity, which is caused by
both genetic and environmental factors, increases
insulin resistance and the risk of type 2. Other
risk factors for type 2 diabetes that may involve a
genetic component include:
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Unhealthy levels of
cholesterol and triglycerides (hyperlipidemia)
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Metabolic syndrome
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High blood pressure
Though a family history of type 2 diabetes is one of
the strongest risk factors for developing the
disease, this genetic predisposition is far more
significant for those who consume an unhealthy,
high-calorie diet and get little exercise.
Gestational diabetes, the form that affects some
women during pregnancy, is also a metabolic disorder
and may have a similar genetic composition to type 2
diabetes.
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