DNA, or deoxyribonucleic acid, is a nucleic acid found in the body.
DNA forms from the repetition of the simple “building blocks of life” called nucleotides.
These nucleotides are made of a phosphate, sugar (deoxyribose), and a nitrogen base.
There are five types of bases, called adenine (A), thymine (T), guanine (G), cytosine (C), and uracil (U).
In a DNA molecule, this basic unit is repeated in a double-helix structure made from two chains of nucleotides linked between the bases.
These are linked either between A and T or between G and C. (There are no other links because these particular base structures do not allow any other combinations.) DNA molecules in a single human cell are extremely long.
In fact, if one were stretched out and laid end to end, it would measure approximately 6.5 feet (2 meters) in length.
The average human body contains 10 billion to 20 billion miles (16 billion to 32 billion kilometers) of DNA distributed among trillions of its cells.
In fact, if the total DNA in all the cells from one human were unraveled, it would stretch to the sun and back more than 500 times.
RNA, or ribonucleic acid, is also a nucleic acid found in the body.
But unlike DNA, it consists of a single chain instead of a double, and the sugar is ribose rather than deoxyribose.
The bases are the same as in DNA, except that the thymine (T) is replaced by another base, uracil (U), which, like the thymine in DNA, links to adenine (A).
All RNA exists in three different forms and depending on the cell is formed either in the central nucleus or in the nucleoid region (an irregularly shaped region within certain types of cells).
What is a mutation?
A mutation is a change (or alteration) in the DNA sequence of a gene.
Although people often use the term “mutant” in a disparaging manner, mutations are important because of the variation they contribute to a population’s gene pool.
Without mutations, there would be no variations and no natural selection within the population, human or otherwise.
But mutations can also create harmful effects that cause diseases and disorders.
One example of a mutation and resulting disease is sickle-cell disease (also called sickle-cell disorder or anemia).
It occurs when a person inherits two abnormal copies of the hemoglobin (the oxygen-carrying protein) gene, one from each parent.
The disease causes red blood cells to become rigid and sickle-like in shape and, thus, unable to carry as much oxygen throughout the body.
Have any genes been found in connection with type 1 diabetes?
To date, researchers have identified several different genes that are believed to make a person more likely to develop type 1 diabetes. But they have not found any one single gene that makes all people who inherit it develop the disease (which is why some family members never develop type 1 diabetes, whereas other siblings do develop the disease). Overall, scientists call the genes they have found “diabetes susceptibility” genes.
What is polygenic diabetes?
Polygenic diabetes is actually what doctors most often refer to when discussing type 1 and type 2 diabetes. This means that there are multiple genes, more than one and often several, that can increase the risk of developing type 1 and type 2 diabetes.
What is monogenic diabetes?
Monogenic diabetes is when a person has one gene mutation that causes diabetes.
It is estimated that of the human body’s 25,000 genes, more than 20 are associated with monogenic diabetes.
An error in one of these single genes can cause an adult or child to develop monogenic diabetes.
It accounts for an estimated 1 to 5 percent of all cases of diabetes, depending on the study.
According to the American Diabetes Association, it is most common in infants, children, and young adults.
Monogenic diabetes includes maturity-onset diabetes in the young (MODY) and neonatal diabetes mellitus (NDM).
Not everyone knows that he or she has this single gene and diabetes, with estimates as high as 80 percent of all cases of monogenic diabetes going undiagnosed.
In fact, if this form of diabetes is not treated correctly, goes undiagnosed, or is confused with type 1 diabetes, it can lead to problems. (See also MODY and NDM, below.)
Is there genetic testing for monogenic diabetes?
Yes, genetic testing can be used to detect monogenic diabetes, but as of this writing, it is often expensive, and some insurance companies do not pay for the screening.
Many health care specialists will test babies who seem to have routine high blood glucose levels.
But not all children who have any type of monogenic diabetes will be diagnosed unless they show classic symptoms that lead the health care professional to test for diabetes.
This is why it is estimated that almost half of all infants who have or will develop a form of monogenic diabetes go undiagnosed.
Who gets neonatal diabetes mellitus (NDM)?
A rare condition called neonatal diabetes mellitus (NDM) appears in neonates, or babies in the first six months of their life. It is caused by a mutation in a single gene and is considered a form of monogenic diabetes. The number of infants born with neonatal diabetes is not precisely known, but it is thought that one in every 100,000 to 500,000 live births, and about one in 400,000 infants, are diagnosed with neonatal diabetes in the first six months of life.
What is polyglandular autoimmune syndrome, type II?
P olyglandular autoimmune syndrome, type II (it is sometimes used interchangeably with Schmidt syndrome) is a rare autoimmune disorder. It most often occurs when there is an extreme lowering of the levels of several hormones from the glands that secrete the hormones. It usually refers to a combination of many diseases, such as Addison’s disease (an autoimmune adrenal [kidney] insufficiency), autoimmune hypothyroidism or hyperthyroidism, type 1 diabetes mellitus, and/or others.
Is there a difference between neonatal diabetes mellitus and type 1 diabetes?
There is a definite difference between neonatal diabetes mellitus (NDM) and type 1 diabetes (the type most associated with children, although it can occur later in life, too). In particular, type 1 diabetes normally appears after the infant’s first six months of life, whereas NDM can affect the health and development of a child beginning at conception.
Why does neonatal diabetes mellitus occur?
The reason for neonatal diabetes mellitus (NDM) has to do with genes.
In fact, to date, more than a dozen different genes (some research suggests more than 20) have been found to cause neonatal diabetes, with some causing both temporary and permanent NDM.
For example, according to the American Diabetes Association, if an infant is born with such a defective gene, he or she may have neonatal diabetes throughout adult life.
Two of the most common single mutated genes are labeled KCNJ11, which represents 30 percent of all cases of permanent neonatal diabetes, and ABCC8, representing about 20 percent.
How are some children affected by neonatal diabetes mellitus (NDM)?
According to the National Institutes of Health, a child’s health can be affected from birth onward if he or she has neonatal diabetes mellitus. For example, some fetuses with NDM may show signs of slow growth, high blood sugar, dehydration, and even difficulty growing after they are born. Children with NDM may also continue to grow more slowly than other children their age, and if the NDM is severe enough, the child may also experience developmental problems.
Can infants outgrow neonatal diabetes mellitus (NDM)?
Yes, some infants will eventually outgrow neonatal diabetes (in that case it’s called transient neonatal diabetes mellitus), while others will have it all their lives (permanent neonatal diabetes mellitus). Nearly 50 percent of the babies born with neonatal diabetes will see the disease disappear by age 18, but the rest will have permanent neonatal diabetes.
What is autoimmunity?
A utoimmunity occurs when the immune system of a person’s body attacks cells that are considered good for the body, mistaking them for foreign cells. This is one reason that scientists believe type 1 diabetes occurs as the autoimmune system attacks the beta cells (the insulin-producing cells) in the pancreas, and the body can no longer make insulin. (For more about beta cells and the pancreas, see the chapter “How Diabetes Affects the Endocrine System”; for more about autoimmunity and the immune system, see the chapter “Diabetes and Body Connections.”)
What are HLAs?
HLAs, or a set of proteins known as human leukocyte antigens, may predispose a person to diabetes.
The HLAs are actually a set of proteins formed by a set of genes.
These genes code for certain proteins called antigens that usually identify a person’s cells as their own cells, in other words, they tell the immune cells not to destroy the cells that are part of the person’s body.
Researchers suggest that some of the HLAs incorrectly tag a person’s own beta cells as “unfriendly,” causing the immune-system cells to attack the beta cells in a form of autoimmunity that can easily affect blood glucose levels.
What is the MODY form of diabetes?
A genetic form of diabetes, caused by a single gene mutation, is called maturity-onset monogenic diabetes of the young, or MODY.
It most often occurs as a child approaches puberty or young adulthood, with most people diagnosed by age 25.
It is thought that 3 to 5 percent of all patients with diabetes have MODY (the numbers vary depending on the study).
It is also estimated that every child born to a parent with MODY has a 50 percent chance of developing the condition.
As for symptoms, the child may or may not show any at all.
Genetically speaking, at least 11 different genes are responsible for the different forms of MODY, and each appears to have different symptoms attached, thus demanding different treatments. For example, according to the Diabetes Genes group in the United Kingdom, people who have a defect in the GCK gene may have hyperglycemia, with an A1c ranging from 5 to 7 percent, with little effect by diet and exercise modification on their blood glucose levels.
Is there a difference between MODY and MODY1?
Yes.
In particular, MODY is “maturity-onset diabetes of the young” and due to mutations in the HNF1A gene, while MODY1 is “maturity-onset diabetes of the young, type 1,” caused by mutations in the gene HNF4A on chromosome 20.
There are also other MODYs, such as MODY2, due to mutations in the GCK gene on chromosome 7, and depending on the mutation, MODY3, MODY4, and so on.
A person with a certain type of MODY will have complications based on the mutation, and in general, these conditions disrupt insulin production.
The most common forms are MODY2 and MODY3.
Why are some treatments given to people with MODY1 often questioned?
M ODY1 occurs when the beta cells in a person’s pancreas, the cells that secrete insulin, are under stress.
Most health care professionals provide the standard therapies given to people with type 2 diabetes in order to make the beta cells secrete more insulin, but a study in 2016 questioned this practice.
Most health care professionals treat MODY1 patients with the standard type 2 diabetes drug therapies, including oral medications that make the pancreas’s insulin-secreting beta cells more active.
But the researchers believe that the type 2 medications given to a person with MODY1 to increase the activity of the beta cells actually increases stress on those cells.
This, in turn, may cause the destruction of the cells, causing even more problems with blood glucose levels.
Thus, many researchers caution professionals who diagnose diabetes in patients to determine whether or not the patient has type 2 or MODY1 diabetes before initiating treatments.