When I was diabetic, I was told by my endocrinologist that Type 2 diabetes was genetic, implying that there was nothing I could have done to prevent it.

When I told my endocrinologist that I planned to reverse my diabetes, he just smiled and said: "Mr. McCulley, the diabetes is in your genes --  it's  hereditary so it's passed down from generation to generation -- and, you can't reverse a genetic disease."

But, that didn't make sense to me. Because of my background in biochemistry, I felt that I could re-program my cells and their DNA to function better -- as they did before I became diabetic.

During my research and during the past several years, I have met a lot of diabetics who had parents, uncles, aunts, brothers and sisters who were also diabetic. Consequently, it appeared that diabetes was truly genetic.

But, this sends a negative message of hopelessness to many diabetics because if they believe it's in their genes, then, they give up because they believe it's out of their control and that there's nothing that they can do.

But, that's not true! Could it be that we are told that diabetes is genetic so  that we'll give up and give in to the drugs being pushed on us by the medical doctors and pharmaceutical companies?

And, how do you explain me being able to reverse my diabetes? And, how do you explain the thousands of other diabetics who have reversinged their diabetes?

Before we go any further, let's look at some definitions for genes, DNA, and chromosomes.

Your body is made up of tiny units called cells – as many as 100 trillion of them. Within the nucleus of every cell is a set of instructions which tell the cell what role it will play in your body. These instructions, essentially a blueprint or recipe for building different parts of the cell, come in the form of a molecule called DNA, which consists of two thread-like strands that are linked together in the shape of a double helix.



DNA (deoxyribonucleic acid) is a long molecule that carries the genetic information within our cells in a compartment called the nucleus.

Each DNA molecule is composed of individual units called bases. There are four types of bases, designated A (adenine), T (thymine), G (guanine), and C (cytosine) that are repeated over and over in pairs.

Each DNA molecule is made of two individual strands paired together. Each strand consists of a series of the four bases. When the two strands pair up, an A on one strand is always across from a T on the other strand, and a C always pairs with a G -- to make up the "rungs" of the DNA ladder. The double-stranded molecule then twists like a coiled ribbon into a shape called a double helix. A piece of DNA millions of base pairs long — in conjunction with some proteins — is a chromosome.

Each “rung,” more accurately called a base pair, is one of three billion such pairs which work together to provide the instructions for building and maintaining a human being – the human genome. The exact order in which these base pairs are combined is called the DNA sequence. Much in the way letters of the alphabet are combined to form words and sentences, the sequence of these bases are the “letters” which spell out the genetic code.

A gene is a distinct portion of a cell’s DNA. Genes are coded instructions for making everything the body needs, especially proteins. Human beings have about 25,000 genes. Researchers have discovered what some of our genes do, and have found some that are associated with disorders (such as cystic fibrosis or Huntington’s disease). There are, though, many genes whose functions are still unknown.

Genes are sections or segments of DNA that form the individual units of heredity. They are carried on the chromosomes and contain instructions for making molecules called proteins. Each protein enables a cell to perform its own special function. The hemoglobin in red blood cells, for example, is responsible for transporting oxygen throughout your body. Another protein, insulin, helps you metabolize your food. The keratin protein is what helps your hair and nails to grow. Other examples: enzymes help us digest food, structural elements give our cells shape, and signaling molecules help the cells communicate with each other.

If you look at DNA as a recipe for creating a living thing, then genes and proteins are the ingredients which work together to build, repair, and run your body.

The traits which make us each unique are also inherited from our ancestors. Physical characteristics such as curly hair, blue eyes, and a tendency for acne are all determined by our genes. Scientists also believe that many emotional and behavioral traits, at least in part, are influenced by an individual’s genetic makeup. Eating habits, intelligence, a penchant for aggressiveness, and even sleeping patterns all have their roots in our DNA.

Because genes are carried on the chromosomes, humans have two copies of each gene, one inherited from the mother and one from the father. The two copies aren’t necessarily the same, however. Just like snowflakes, genes come in variant forms. These variations are known as alleles. Different alleles are what produce variations in inherited traits. This is why your individual traits such as hair color or blood type may not match those traits in either of your parents.

Additional bases that come before the genes on a chromosome tell cells when each gene should be used. For example, these sequences might contain instructions that a protein for making hair should only be made in certain skin cells, and not by other cells of the body.

How do we inherit our genes?
Humans inherit 23 chromosomes from each of their parents for a total of 46 chromosomes. Of these, 44 are identical in men and women — these are called autosomes. The remaining two chromosomes are called sex chromosomes, which are designated X and Y. Women inherit two X chromosomes, whereas men inherit one X chromosome from their mother and one Y chromosome from their father.

Because of the way we inherit our chromosomes, we all have two copies of every gene that is contained on the autosomes. Depending on the combination of the genes we inherit, we end up with some traits that resemble our mother and others that resemble our father. Women have two copies of each gene on the X chromosome, while men have only the genes that they inherit from their mother on the X chromosome and only genes that they inherit from their father on the Y chromosome.

Proteins are chains of chemical building blocks called amino acids. A protein could contain just a few amino acids in its chain or it could have several thousands. Proteins form the basis for most of what the body does, such as digestion, making energy and growing.

A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. Chromosomes are "bundles" of genes that determine your body's makeup. Humans have 23 pairs of chromosomes (for a total of 46). Of those, 1 pair is the sex chromosomes (determining whether you are male or female, plus some other body characteristics), and the other 22 pairs are autosomal chromosomes (determining the rest of your body’s makeup).

A marker is a segment of DNA with known genetic characteristics. These markers, which can be found at specific locations, or loci, on the chromosome, are essentially places where the same pattern repeats a number of times – sort of a "stutter" in the DNA. The number of repeats in a marker is known as an allele, basically a variant form of a specific gene. Since the number of repeats within these sequences is inherited, they make useful mileposts for genetic testing.

A special type of marker known as a Short Tandem Repeat (STR) is the one most often used for hereditary and forensic testing. STRs are short sequences of DNA (usually 2-5 base pairs) that are repeated as many as 100 times along the DNA strand. For example, the four-base pattern CAGT might be repeated four times: CAGTCAGTCAGTCAGT. STRs are chosen for their tendencies to display variations, caused by mutations, among different people, allowing scientists to differentiate between individuals.

To determine a connection between two individuals, specific markers on the DNA strand are analyzed for the number of repetitions at each marker. Because mutations happen randomly, however, a mutation which appears at a specific marker may have begun with the current generation, or it may have been handed down through five generations. This is why a number of different markers are tested and compared. The number of markers examined varies from test to test and company to company, but most ancestry DNA tests are typically in the 12-40 marker range. The DNA test results provide you with the number of repetitions at each of the specific markers tested. The more locations that match, the more likely it is that the two individuals are related.

In all organisms, there are two major steps separating a protein-coding gene from its protein: First, the DNA on which the gene resides must be transcribed from DNA to messenger RNA (mRNA); and, second, it must be translated from mRNA to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule itself is called a gene product.

The genetic code is the set of rules by which a gene is translated into a functional protein. Each gene consists of a specific sequence of nucleotides encoded in a DNA (or sometimes RNA) strand; a correspondence between nucleotides, the basic building blocks of genetic material, and amino acids, the basic building blocks of proteins, must be established for genes to be successfully translated into functional proteins.

The human genome is a complete copy of the entire set of human gene instructions.

A mutation occurs when one or more of the pairs of As, Ts, Cs, and Gs is out of order. This changes the coding for one or more genes, and is called genetic mutation. A mutation may be disease-causing or harmless.

As DNA passes from one generation to the next, it acquires small changes, known as mutations. The most common is a change to a single base, for example a change from a T to a C. Other possible changes include the loss or addition of one or more bases. The effect of a mutation depends upon the type of changes and their location in the sequence. Just like one single letter can change a word or even a sentence, a mutation can change the instructions in a gene. Most mutations are considered to be neutral, having little to no impact. Serious mutations can actually cause a protein to stop functioning properly.

Mutations in the DNA can be inherited or acquired. When a mutation is inherited from a parent it is present in almost all of the body’s cells. Acquired mutations are changes in the DNA that develop throughout a person’s life. They arise in the DNA of individual cells, either spontaneously, or in response to environmental factors such as radiation or viruses. Spontaneous mutations are the most common, caused by copying mistakes in the DNA code as cells form and divide. Most of the time the cell recognizes the mistake and repairs it, but sometimes it passes the mutation on as it divides and creates new cells.

DNA doesn’t have long-term memory, so any mutations which develop in a gene are reproduced and passed down to future generations. By comparing the mutations of two individuals, it is possible to calculate how closely they’re related. By calculating the mutation rate, researchers can deduce how far back in time different groups split apart.

Some mutations result in proteins that do not function normally, and may end up causing disease. There are several ways that gene mutation can change the way a protein functions, including:

• Altered function: Some mutations result in a protein that cannot carry out its normal function in the cell, or cannot carry out that function very well. One example of this type of mutation is sickle cell anemia. In this disorder, an altered protein in red blood cells alters the shape of the red blood cell, which causes the cell to become stuck in blood vessels. This prevents cells from carrying sufficient oxygen to the rest of the body.
• Lack of protein: Some mutations prevent the protein from being made. One example of this type of mutation is hemophilia. In this condition, a mutation results in the absence of a protein that causes blood to clot. The result is uncontrolled bleeding in response to injury.
• Change in how much protein is made: Some mutations cause too much or too little of a normal protein to be made. Although the protein itself functions properly, it is not present in quantities that are appropriate. One example of this is in the development of some cancers. In this case, a protein that prevents additional mutations from building up can become turned off. Without this protein, the cell accumulates mutations and becomes increasingly cancerous.

Genetic and Diabetes

Type 2 diabetes (T2D) is a multi-factorial disease, i.e. it is influenced by both genetic and environmental factors. People with a family history of  diabetes are at higher risk of developing it themselves since they share genetic background, but, more importantly, they share similar environments, similar behaviors, similar lifestyles, similar eating habits, and similar cooking habits. Consequently, if you change the environment and behaviors, you can prevent the development of the disease!

It has been estimated that 70%-80% of  T2D risk is environmentally and behaviorally controlled, and 20-30% genetic, with multiple genes involved and different combinations of genes playing roles in different subsets of individuals. It is not yet known how many genes are involved or how much control each exerts over the development of the disease, but recent research has identified a number of promising candidates.

The gene showing the strongest association so far with T2D is TCF7L2. Variations in TCF7L2 are associated with impaired insulin secretion and increased hepatic glucose production, which may partially explain the development of T2D in people carrying TCF7L2 variations. People who carry one copy of a variant TCF7L2 have an approximately 1.5 times increased risk of T2D, while people who carry two copies of a variant have an approximately 2.4 times increase risk. About 7% of the U..population carries two copies of the variant.  TCF7L2 is a transcription factor involved in cell proliferation and in adipogenesis, myogenesis, and pancreatic islet development.  It activates the genes encoding intestinal proglucagon and glucagon-like peptides-1 and -2.2 Its effect on the expression of these genes likely explains its association with T2D.

Genome-wide association studies have uncovered a number of other promising candidate genes. Among them are SLC30A8, a zinc transporter that makes zinc available for cocrystallization with and subsequent secretion of insulin; and PPARγ, a receptor that controls the expression of several genes and affects insulin sensitivity.  Variations in each of the candidate genes alone increase the risk for T2D modestly.  However, there is a stepwise increase in T2D risk as the number of variations carried by a single person increases. People who carry more than 12 variants are at greatest risk.  But,  even with this higher risk profile, they don't develop the disease if they eat and live a healthy lifestyle!

Identifying Type 2 Diabetes Genes

Although researchers know from studying family histories that you can inherit a risk for Type 2 diabetes, they have had difficulty identifying specific gene mutations that cause the disease.

Some of the problems include:

• Number of genes: Many genes are involved in controlling our fuel intake and regulation. A mutation in any one gene will not lead to diabetes, but mutations in several genes could add up to pose an increased risk. Any two people with Type 2 diabetes may have mutations in a different subset of genes, making it hard for researchers to pinpoint high-risk mutations.
• Environmental influence: A person's lifestyle and environment play a larger role in whether or not they develop Type 2 diabetes. Two people may have the same risk and the same gene mutations, but if one person controls their weight and exercises regularly, that person will not develop diabetes. If two people have the same mutation but different outcomes, researchers have a hard time distinguishing which genes are important in the disease.
• Inherited Lifestyle: We inherit more than just genes from our parents; we also inherit lifestyle. Poor eating habits and lack of exercise are learned behaviors that children pick up from their parents. This type of inheritance has nothing to do with genes, and makes it hard for researchers to identify a genetic risk for diabetes.

Despite these problems, researchers have found a few gene mutations that influence diabetes risk in some families. One well studied gene is the Beta3-adrenergic receptor gene.

The Beta3-Adrenergic Receptor Gene
The Beta3-adrenergic receptor gene makes a protein in fat cells that is involved in determining how much fuel your body burns when you are resting. A mutation in this gene slows down how quickly a person burns fat — increasing their tendency to be obese. One specific mutation in this gene, called TRP64ARG, is almost four times more common in Pima Indians than in people of European descent, and is one and a half times more common in people of African or Mexican descent. The prevalence of the TRP64ARG gene mutation in these populations probably accounts at least in part for why these ethnic groups have a higher rate of Type 2 diabetes. However, the environment they live in and the lack of access to fresh vegetables and fruits are more significant factors that drive them becoming diabetic.

People with two copies of the TRP64ARG mutation have a slower metabolism than people without the mutation. Therefore, they tend to be more obese — even in mutation carriers who do not go on to develop diabetes. They also have a harder time losing weight than the general population. In addition, people with the TRP64ARG mutation develop diabetes at an earlier age than Type 2 diabetics without the mutation. This mutation is not present in all Type 2 diabetics, but it appears to change the course of diabetes in those who carry it.

The TRP64ARG mutation causes the Beta3-adrenergic receptor gene to make a different protein sequence. The name is an abbreviation for the change in the protein caused by the mutation. The altered protein has the amino acid Arginine (ARG) at the 64th position, rather than the amino acid Tryptophan (TRP). This switch in amino acid building blocks prevents the protein from working properly.

The Beta3-adrenergic receptor gene is not the only gene that regulates how we metabolize fat. Researchers think that mutations in similar genes may also put a person at risk for diabetes. So far, they have not found common mutations in these genes that cause diabetes, but they continue to discover that lifestyle and eating habits have a more significant impact on people becoming diabetic than any other factor.

Genetic Testing
The genetics of Type 2 diabetes is complicated, with many different genes influencing a person's risk. Because of this array of genes, Type 2 diabetes is not inherited in a clearly dominant or recessive manner -- unlike a disease such as cystic fibrosis, which is carried as a recessive gene and passed down from the parent to the child.

A person may have one gene that increases their risk and other genes that decrease risk. Together, these genes, along with environmental factors, determine a person's overall risk for developing diabetes. With so many variables to consider, the medical community is a long way from a genetic test for Type 2 diabetes.

Please Note: Since there is no genetic test for Type 2 diabetes, it is imperative that you get specific annual physical exams and blood tests for fasting blood glucose, glucose tolerance, and hemoglobin A1C. In addition, try to  eat a plant-based diet and avoid the foods that fuel diseases such as diabetes, i.e. bread, pasta, potatoes, processed foods, fast foods, soda, etc.

Key Point: Our diet has some impact on our genetic code which is passed on to the next generation. The more nutritious our diet the stronger will be the genes which will get passed on. We are what we eat. But to some extent, our children and grandchildren are what we eat also.

For more information about how your diet affects the way genes are expressed, the effect of genes on how the body uses nutrients, and the effects of nutrients on molecular level processes in the body, refer to this web page.


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