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 asmutations. 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:
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!
Some of the problems include:
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.
References
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 asmutations. 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 inseveral 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 largerrole 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.
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.
References
- Genetic Services Policy Project. (2008) Type 2 Diabetes and Genetic Technology: A Policy Brief. Available at http://depts.washington.edu/genpol/docs/PolicyBriefT2D.pdf. Accessed November 20, 2008.
- Doria A, Patti M-E, and Khan CR. (2008) The Emerging Genetic Architecture of Type 2 Diabetes. Cell Metabolism 8, 186-200.
- ^ a b Pearson H (2006). "Genetics: what is a gene?". Nature 441 (7092): 398–401.doi:10.1038/441398a. PMID 16724031.
- ^ a b c Elizabeth Pennisi (2007). "DNA Study Forces Rethink of What It Means to Be a Gene".Science 316 (5831): 1556–1557. doi:10.1126/science.316.5831.1556. PMID 17569836.
- ^ a b Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (2006). "RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse". Nature 441(7092): 469–74. doi:10.1038/nature04674. PMID 16724059.
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- Walston, J., et al. (1995). Time of onset of non-insulin dependent diabetes mellitus and genetic variation in the B(3)-adrenergic receptor gene. N Engl J Med, 333, 343-347.
- Silver, K., et al. (1997). TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans. Hum Genet, 101, 306-311.
- Kadowaki, H., et al. (1995). A mutation in the beta 3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects. Biochem Biophys Res Commun, 215, 555-560.
- Widen, E., et al. (1995). Association of a polymorphism in the B(3)-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med, 333, 348-351.
- Clement, K., et al. (1995). Genetic variation in the B(3)-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med, 333, 352-354.
- Michael L. Stitzel, Praveen Sethupathy, Daniel S. Pearson, Peter S. Chines, Lingyun Song, Michael R. Erdos, Ryan Welch, Stephen C.J. Parker, Alan P. Boyle, Laura J. Scott, Elliott H. Margulies, Michael Boehnke, Terrence S. Furey, Gregory E. Crawford, Francis S. Collins. Global Epigenomic Analysis of Primary Human Pancreatic Islets Provides Insights into Type 2 Diabetes Susceptibility Loci. Cell Metabolism, 2010; 12 (5): 443-455 DOI:10.1016/j.cmet.2010.09.012
- Defronzo RA: Lilly Lecture 1987: the triumvirate: β-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes37 :667 –687,1988
- Permutt MA, Wasson JC, Suarez BK, Lin J, Thomas J, Meyer J, Lewitzky S, Rennich JS, Parker A, Duprat L, Maruti S, Chayen S, Glaser B: A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population. Diabetes50 :681 –685,2001
- Risch N, de Leon D, Ozelius L, Kramer P, Almasy L, Singer B, Fahn S, Breakefield X, Bressman S: Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nat Genet9 :152 –159,1995
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- Ghosh S, Watanabe RM, Hauser ER, Valle T, Magnuson VL, Erdos MR, Langefeld CD, Balow J, Ally DS, Kohtamaki K, Chines P, Birznieks G, Kaleta HS, Musick A, Te C, Tannenbaum J, Eldridge W, Shapiro S, Martin C, Witt A, So A, Chang J, Shurtleff B, Porter R, Kudelko K: Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs. Proc Natl Acad Sci U S A96 :2198 –2203,1999
Sickle Cell Anemia
Sickle-cell disease (SCD), or sickle-cell anaemia (SCA) or drepanocytosis, is a hereditary blood disorder, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various complications. The sickling occurs because of a mutation in the hemoglobin gene. Individuals with one copy of the defunct gene display both normal and abnormal hemoglobin. This is an example of codominance.
Life expectancy is shortened. In 1994, in the US, the average life expectancy of persons with this condition was estimated to be 42 years in males and 48 years in females, but today, thanks to better management of the disease, patients can live into their 70s or beyond.
Sickle-cell disease occurs more commonly among people whose ancestors lived in tropical and sub-tropical sub-saharan regions where malaria is or was common. Where malaria is common, carrying a single sickle-cell gene (sickle cell trait) confers a fitness. Specifically, humans with one of the two alleles of sickle-cell disease show less severe symptoms when infected with malaria.
Sickle-cell anemia is a form of sickle-cell disease in which there is homozygosity for the mutation that causes HbS. Sickle-cell anemia is also referred to as "HbSS", "SS disease", "hemoglobin S" or permutations of those names. In heterozygous people, that is, those who have only one sickle gene and one normal adult hemoglobin gene, the condition is referred to as "HbAS" or "sickle cell trait". Other, rarer forms of sickle-cell disease are compound heterozygous states in which the person has only one copy of the mutation that causes HbS and one copy of another abnormal hemoglobin allele. They include sickle-hemoglobin C disease (HbSC), sickle beta-plus-thalassaemia (HbS/β+) and sickle beta-zero-thalassaemia (HbS/β0).
The term disease is applied because the inherited abnormality causes a pathological condition that can lead to death and severe complications. Not all inherited variants of hemoglobin are detrimental, a concept known as genetic polymorphism.
Genetics
Normally, humans have Hemoglobin A, which consists of two alpha and two beta chains, Hemoglobin A2, which consists of two alpha and two delta chains and Hemoglobin F, consisting of two alpha and two gamma chains in their bodies. Of these, Hemoglobin A makes up around 96-97% of the normal hemoglobin in humans.Sickle-cell gene mutation probably arose spontaneously in different geographic areas, as suggested by restriction endonuclease analysis. These variants are known as Cameroon, Senegal, Benin, Bantu and Saudi-Asian. Their clinical importance springs from the fact that some of them are associated with higher HbF levels, e.g., Senegal and Saudi-Asian variants, and tend to have milder disease.
In people heterozygous for HgbS (carriers of sickling hemoglobin), the polymerisation problems are minor, because the normal allele is able to produce over 50% of the hemoglobin. In people homozygous for HgbS, the presence of long-chain polymers of HbS distort the shape of the red blood cell from a smooth doughnut-like shape to ragged and full of spikes, making it fragile and susceptible to breaking within capillaries. Carriers have symptoms only if they are deprived of oxygen (for example, while climbing a mountain) or while severely dehydrated.
The sickle-cell disease occurs when the sixth amino acid, glutamic acid, is replaced by valine to change its structure and function; as such, sickle cell anemia is also known as E6V. Valine is hydrophobic, causing the hemoglobin to collapse in on itself occasionally. The structure is not changed otherwise. When enough hemoglobin collapses in on itself the red blood cells become sickle-shaped.
The gene defect is a known mutation of a single nucleotide (see single-nucleotide polymorphism - SNP) (A to T) of the β-globin gene, which results in glutamic acid being substituted by valine at position 6. Hemoglobin S with this mutation is referred to as HbS, as opposed to the normal adult HbA. The genetic disorder is due to the mutation of a single nucleotide, from a GAG to GTG codon on the coding strand, which is transcribed from the template strand into a GUG codon. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or quaternary structure of hemoglobin in conditions of normal oxygen concentration. What it does allow for, under conditions of low oxygen concentration, is the polymerization of the HbS itself. The deoxy form of hemoglobin exposes a hydrophobic patch on the protein between the E and F helices. The hydrophobic residues of the valine at position 6 of the beta chain in hemoglobin are able to associate with the hydrophobic patch, causing hemoglobin S molecules to aggregate and form fibrous precipitates.
The allele responsible for sickle-cell anemia can be found on the short arm of chromosome 11. A person that receives the defective gene from both father and mother develops the disease; a person that receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the disease and a 1-in-2 chance of their child being just a carrier. Heterozygotes are still able to contract malaria, but their symptoms are generally less severe.
Due to the adaptive advantage of the heterozygote, the disease is still prevalent, especially among people with recent ancestry in malaria-stricken areas, such as Africa, the Mediterranean, India and the Middle East. Malaria was historically endemic to southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases.
The malaria parasite has a complex life cycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cells with defective hemoglobin to rupture prematurely, making the plasmodium unable to reproduce. Further, the polymerization of Hb affects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people's chances of survival actually increase if they carry sickle-cell trait (selection for the heterozygote).
In the USA, where there is no endemic malaria, the prevalence of sickle-cell anemia among blacks is lower (about 0.25%) than in West Africa (about 4.0%) and is falling. Without endemic malaria, the sickle cell mutation is purely disadvantageous and will tend to be selected out of the affected population via natural selection.
However, the African American community of the USA is known to be the result of significant admixture between several African and non-African ethnic groups, and also represents the descendants of survivors of the slavery and the slave trade. Thus, a lower degree of endogamy and, particularly, abnormally high health-selective pressure through slavery may be the most plausible explanations for the lower prevalence of sickle-cell anemia (and, possibly, other genetic diseases) among African-Americans compared to Sub-Saharan Africans. Another factor limiting the spread of sickle-cell genes in North America is the absence of cultural proclivities to polygamy, which allows affected males to continue to seek unaffected children with multiple partners.
Inheritance Probability
Sickle-cell conditions are inherited from parents in much the same way as blood type, hair color and texture, eye color, and other physical traits. The types of hemoglobin a person makes in the red blood cells depend on what hemoglobin genes are inherited from his parents. If one parent has sickle-cell anemia (SS) and the other has sickle-cell trait then there is a 50% chance of a child's having sickle-cell disease and a 50% chance of a child's having sickle-cell trait. When both parents have sickle-cell trait a child has a 25% chance of sickle-cell disease, as shown in the diagram.
Medical Treatment Strategies
Folic acid and penicillin: Children born with sickle-cell disease will undergo close observation by the pediatrician and will require management by a hematologist to assure they remain healthy. These patients will take a 1 mg dose of folic acid daily for life. From birth to five years of age, they will also have to take penicillin daily due to the immature immune system that makes them more prone to early childhood illnesses.
Folic acid, which is one of the B-complex vitamins, is important for allowing the body to make new cells. It is especially important in situations in which the body is rapidly making new cells as it is needed for the formation of DNA and RNA, which are two important types of genetic molecules which are needed to make new cells. Deficiencies in folic acid can impair the manufacture of new red blood cells, the Office of Dietary Supplements explains.
People who have sickle cell anemia typically have increased needs for folic acid, "US News and World Report" explains. One of the consequences of sickle cell anemia is that the abnormally shaped red blood cells are broken down more quickly, which forces the body to make new red blood cells more frequently. In order to do this, larger amounts of folic acid are needed, so people with sickle cell anemia may need to increase their folic acid intake.
Folic Acid Sources and Dosage: Many foods contain folic acid. Many breakfast cereals are fortified with folic acid, the Office of Dietary Supplements notes. Folic acid can also be found in beef liver, beans, legumes and green leafy vegetables such as spinach, broccoli and asparagus. If you are having trouble getting enough folic acid in your diet, you may need to take folic acid supplements. Folic acid is not considered to be toxic, but taking more than 1,000 mcg per day is not usually recommended because it can mask a vitamin B-12 deficiency.
Malaria chemoprophylaxis: The protective effect of sickle cell trait does not apply to people with sickle cell disease; in fact, they are uniquely vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. It has therefore been recommended that people with sickle cell disease living in malarial countries should receive anti-malarial chemoprophylaxis for life.
Vaso-occlusive crises: Most people with sickle-cell disease have intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises, however, vary tremendously. Painful crises are treated symptomatically with analgesics; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) devices are commonly used in this setting. Diphenhydramine is also an effective agent that is frequently prescribed by doctors in order to help control any itching associated with the use of opioids.
Acute chest crisis: Management is similar to vaso-occlusive crisis, with the addition of antibiotics (usually a quinolone or macrolide, since cell wall-deficient ["atypical"] bacteria are thought to contribute to the syndrome), oxygen supplementation for hypoxia, and close observation. Should the pulmonary infiltrate worsen or the oxygen requirements increase, simple blood transfusion or exchange transfusion is indicated. The latter involves the exchange of a significant portion of the patients red cell mass for normal red cells, which decreases the percent of hemoglobin S in the patient's blood.
Hydroxyurea: The first approved drug for the causative treatment of sickle-cell anemia, hydroxyurea, was shown to decrease the number and severity of attacks in a study in 1995 (Charache et al.) and shown to possibly increase survival time in a study in 2003 (Steinberg et al.). This is achieved, in part, by reactivating fetal hemoglobin production in place of the hemoglobin S that causes sickle-cell anemia. Hydroxyurea had previously been used as a chemotherapy agent, and there is some concern that long-term use may be harmful, but this risk has been shown to be either absent or very small and it is likely that the benefits outweigh the risks.
Transfusion therapy: Blood transfusions are often used in the management of sickle cell disease in acute cases and to prevent complications by decreasing the number of red blood cells (RBC) that can sickle by adding normal red blood cells. In children prophylactic chronic red blood cell (RBC) transfusion therapy has been shown to be efficacious to a certain extent in reducing the risk of first stroke or silent stroke when transcranial Doppler (TCD) ultrasonography shows abnormal increased cerebral blood flow velocities. In those who have sustained a prior stroke event it also reduces the risk of recurrent stroke and additional silent strokes.
Bone marrow transplants: Bone marrow transplants have proven to be effective in children. Bone marrow transplants are the only known cure for SCD.
Life expectancy is shortened. In 1994, in the US, the average life expectancy of persons with this condition was estimated to be 42 years in males and 48 years in females, but today, thanks to better management of the disease, patients can live into their 70s or beyond.
Sickle-cell disease occurs more commonly among people whose ancestors lived in tropical and sub-tropical sub-saharan regions where malaria is or was common. Where malaria is common, carrying a single sickle-cell gene (sickle cell trait) confers a fitness. Specifically, humans with one of the two alleles of sickle-cell disease show less severe symptoms when infected with malaria.
Sickle-cell anemia is a form of sickle-cell disease in which there is homozygosity for the mutation that causes HbS. Sickle-cell anemia is also referred to as "HbSS", "SS disease", "hemoglobin S" or permutations of those names. In heterozygous people, that is, those who have only one sickle gene and one normal adult hemoglobin gene, the condition is referred to as "HbAS" or "sickle cell trait". Other, rarer forms of sickle-cell disease are compound heterozygous states in which the person has only one copy of the mutation that causes HbS and one copy of another abnormal hemoglobin allele. They include sickle-hemoglobin C disease (HbSC), sickle beta-plus-thalassaemia (HbS/β+) and sickle beta-zero-thalassaemia (HbS/β0).
The term disease is applied because the inherited abnormality causes a pathological condition that can lead to death and severe complications. Not all inherited variants of hemoglobin are detrimental, a concept known as genetic polymorphism.
Genetics
Normally, humans have Hemoglobin A, which consists of two alpha and two beta chains, Hemoglobin A2, which consists of two alpha and two delta chains and Hemoglobin F, consisting of two alpha and two gamma chains in their bodies. Of these, Hemoglobin A makes up around 96-97% of the normal hemoglobin in humans.Sickle-cell gene mutation probably arose spontaneously in different geographic areas, as suggested by restriction endonuclease analysis. These variants are known as Cameroon, Senegal, Benin, Bantu and Saudi-Asian. Their clinical importance springs from the fact that some of them are associated with higher HbF levels, e.g., Senegal and Saudi-Asian variants, and tend to have milder disease.
In people heterozygous for HgbS (carriers of sickling hemoglobin), the polymerisation problems are minor, because the normal allele is able to produce over 50% of the hemoglobin. In people homozygous for HgbS, the presence of long-chain polymers of HbS distort the shape of the red blood cell from a smooth doughnut-like shape to ragged and full of spikes, making it fragile and susceptible to breaking within capillaries. Carriers have symptoms only if they are deprived of oxygen (for example, while climbing a mountain) or while severely dehydrated.
The sickle-cell disease occurs when the sixth amino acid, glutamic acid, is replaced by valine to change its structure and function; as such, sickle cell anemia is also known as E6V. Valine is hydrophobic, causing the hemoglobin to collapse in on itself occasionally. The structure is not changed otherwise. When enough hemoglobin collapses in on itself the red blood cells become sickle-shaped.
The gene defect is a known mutation of a single nucleotide (see single-nucleotide polymorphism - SNP) (A to T) of the β-globin gene, which results in glutamic acid being substituted by valine at position 6. Hemoglobin S with this mutation is referred to as HbS, as opposed to the normal adult HbA. The genetic disorder is due to the mutation of a single nucleotide, from a GAG to GTG codon on the coding strand, which is transcribed from the template strand into a GUG codon. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or quaternary structure of hemoglobin in conditions of normal oxygen concentration. What it does allow for, under conditions of low oxygen concentration, is the polymerization of the HbS itself. The deoxy form of hemoglobin exposes a hydrophobic patch on the protein between the E and F helices. The hydrophobic residues of the valine at position 6 of the beta chain in hemoglobin are able to associate with the hydrophobic patch, causing hemoglobin S molecules to aggregate and form fibrous precipitates.
The allele responsible for sickle-cell anemia can be found on the short arm of chromosome 11. A person that receives the defective gene from both father and mother develops the disease; a person that receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the disease and a 1-in-2 chance of their child being just a carrier. Heterozygotes are still able to contract malaria, but their symptoms are generally less severe.
Due to the adaptive advantage of the heterozygote, the disease is still prevalent, especially among people with recent ancestry in malaria-stricken areas, such as Africa, the Mediterranean, India and the Middle East. Malaria was historically endemic to southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases.
The malaria parasite has a complex life cycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cells with defective hemoglobin to rupture prematurely, making the plasmodium unable to reproduce. Further, the polymerization of Hb affects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people's chances of survival actually increase if they carry sickle-cell trait (selection for the heterozygote).
In the USA, where there is no endemic malaria, the prevalence of sickle-cell anemia among blacks is lower (about 0.25%) than in West Africa (about 4.0%) and is falling. Without endemic malaria, the sickle cell mutation is purely disadvantageous and will tend to be selected out of the affected population via natural selection.
However, the African American community of the USA is known to be the result of significant admixture between several African and non-African ethnic groups, and also represents the descendants of survivors of the slavery and the slave trade. Thus, a lower degree of endogamy and, particularly, abnormally high health-selective pressure through slavery may be the most plausible explanations for the lower prevalence of sickle-cell anemia (and, possibly, other genetic diseases) among African-Americans compared to Sub-Saharan Africans. Another factor limiting the spread of sickle-cell genes in North America is the absence of cultural proclivities to polygamy, which allows affected males to continue to seek unaffected children with multiple partners.
Inheritance Probability
Sickle-cell conditions are inherited from parents in much the same way as blood type, hair color and texture, eye color, and other physical traits. The types of hemoglobin a person makes in the red blood cells depend on what hemoglobin genes are inherited from his parents. If one parent has sickle-cell anemia (SS) and the other has sickle-cell trait then there is a 50% chance of a child's having sickle-cell disease and a 50% chance of a child's having sickle-cell trait. When both parents have sickle-cell trait a child has a 25% chance of sickle-cell disease, as shown in the diagram.
Medical Treatment Strategies
Folic acid and penicillin: Children born with sickle-cell disease will undergo close observation by the pediatrician and will require management by a hematologist to assure they remain healthy. These patients will take a 1 mg dose of folic acid daily for life. From birth to five years of age, they will also have to take penicillin daily due to the immature immune system that makes them more prone to early childhood illnesses.
Folic acid, which is one of the B-complex vitamins, is important for allowing the body to make new cells. It is especially important in situations in which the body is rapidly making new cells as it is needed for the formation of DNA and RNA, which are two important types of genetic molecules which are needed to make new cells. Deficiencies in folic acid can impair the manufacture of new red blood cells, the Office of Dietary Supplements explains.
People who have sickle cell anemia typically have increased needs for folic acid, "US News and World Report" explains. One of the consequences of sickle cell anemia is that the abnormally shaped red blood cells are broken down more quickly, which forces the body to make new red blood cells more frequently. In order to do this, larger amounts of folic acid are needed, so people with sickle cell anemia may need to increase their folic acid intake.
Folic Acid Sources and Dosage: Many foods contain folic acid. Many breakfast cereals are fortified with folic acid, the Office of Dietary Supplements notes. Folic acid can also be found in beef liver, beans, legumes and green leafy vegetables such as spinach, broccoli and asparagus. If you are having trouble getting enough folic acid in your diet, you may need to take folic acid supplements. Folic acid is not considered to be toxic, but taking more than 1,000 mcg per day is not usually recommended because it can mask a vitamin B-12 deficiency.
Malaria chemoprophylaxis: The protective effect of sickle cell trait does not apply to people with sickle cell disease; in fact, they are uniquely vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. It has therefore been recommended that people with sickle cell disease living in malarial countries should receive anti-malarial chemoprophylaxis for life.
Vaso-occlusive crises: Most people with sickle-cell disease have intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises, however, vary tremendously. Painful crises are treated symptomatically with analgesics; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) devices are commonly used in this setting. Diphenhydramine is also an effective agent that is frequently prescribed by doctors in order to help control any itching associated with the use of opioids.
Acute chest crisis: Management is similar to vaso-occlusive crisis, with the addition of antibiotics (usually a quinolone or macrolide, since cell wall-deficient ["atypical"] bacteria are thought to contribute to the syndrome), oxygen supplementation for hypoxia, and close observation. Should the pulmonary infiltrate worsen or the oxygen requirements increase, simple blood transfusion or exchange transfusion is indicated. The latter involves the exchange of a significant portion of the patients red cell mass for normal red cells, which decreases the percent of hemoglobin S in the patient's blood.
Hydroxyurea: The first approved drug for the causative treatment of sickle-cell anemia, hydroxyurea, was shown to decrease the number and severity of attacks in a study in 1995 (Charache et al.) and shown to possibly increase survival time in a study in 2003 (Steinberg et al.). This is achieved, in part, by reactivating fetal hemoglobin production in place of the hemoglobin S that causes sickle-cell anemia. Hydroxyurea had previously been used as a chemotherapy agent, and there is some concern that long-term use may be harmful, but this risk has been shown to be either absent or very small and it is likely that the benefits outweigh the risks.
Transfusion therapy: Blood transfusions are often used in the management of sickle cell disease in acute cases and to prevent complications by decreasing the number of red blood cells (RBC) that can sickle by adding normal red blood cells. In children prophylactic chronic red blood cell (RBC) transfusion therapy has been shown to be efficacious to a certain extent in reducing the risk of first stroke or silent stroke when transcranial Doppler (TCD) ultrasonography shows abnormal increased cerebral blood flow velocities. In those who have sustained a prior stroke event it also reduces the risk of recurrent stroke and additional silent strokes.
Bone marrow transplants: Bone marrow transplants have proven to be effective in children. Bone marrow transplants are the only known cure for SCD.
From the Death to Diabetes Office:
We are not experts when it comes to sickle cell anemia. But, what we have discovered is that following a plant-based diet not only works for diabetes, it also works for other diseases. Why? Because plants contain the missing nutrients that our bodies require to be healthy.
Sickle cell disease is an inherited blood disorder. Normally, red blood cells are disc-shaped and flexible. In sickle cell disease, however, hemoglobin (the chemical within red blood cells that carries oxygen around the body) is abnormal. This defect causes red blood cells to collapse into a crescent, or sickle, shape.
These abnormal blood cells are destroyed at an unusually high rate, causing a shortage of red blood cells (anemia). In addition, they can suddenly clump together and clog up small blood vessels throughout the body. This clumping causes what is called a sickle cell crisis.
When blood vessels are blocked by sickle-shaped red blood cells, parts of the body are deprived of oxygen. This can cause severe pain and damage to the organs and tissues that are deprived.
Common triggers of sickle cell crisis include smoking, exercise, exposure to high altitudes, fever, infection, dehydration, and the drop in oxygen or changes in air pressure that can occur during airplane travel.
Treatment involves managing the anemia, chronic pain, and organ damage caused by sickle cell disease. Of course, it is also important to minimize exposure to conditions or situations that can trigger sickle cell crisis.
Natural Healing Solutions for Sickle Cell Anemia
There is no cure for sickle cell anemia. However, there are things that one can do to live a better quality of life.
From a nutritional perspective, the best thing that you can do is to follow a plant-based macro-nutrient-dense and anti-inflammatory diet (such as the Death to Diabetes Diet), while avoiding processed foods, white rice, pasta, flour, wheat, gluten, most dairy, and, of course, soda, diet soda, and fast foods.
Importance of Folic Acid
One of the consequences of sickle cell anemia is that the abnormally shaped red blood cells are broken down more quickly, which forces the body to make new red blood cells more frequently.
The body needs folic acid, which is important for allowing the body to make new cells. Folic acid is especially important in situations in which the body is rapidly making new cells as it is needed for the formation of DNA and RNA, which are two important types of genetic molecules which are needed to make new cells.
Instead of taking a folic acid supplement, ensure that you eat lots of greens (collards, turnip, mustard), and green leafy vegetables such as spinach, broccoli, asparagus, Brussels sprouts, and Romaine lettuce. Other foods include okra, beans, legumes, avocado, cauliflower, and citrus fruits.
From a nutritional perspective, the best thing that you can do is to follow a plant-based macro-nutrient-dense and anti-inflammatory diet (such as the Death to Diabetes Diet), while avoiding processed foods, white rice, pasta, flour, wheat, gluten, most dairy, and, of course, soda, diet soda, and fast foods.
Importance of Folic Acid
One of the consequences of sickle cell anemia is that the abnormally shaped red blood cells are broken down more quickly, which forces the body to make new red blood cells more frequently.
The body needs folic acid, which is important for allowing the body to make new cells. Folic acid is especially important in situations in which the body is rapidly making new cells as it is needed for the formation of DNA and RNA, which are two important types of genetic molecules which are needed to make new cells.
Instead of taking a folic acid supplement, ensure that you eat lots of greens (collards, turnip, mustard), and green leafy vegetables such as spinach, broccoli, asparagus, Brussels sprouts, and Romaine lettuce. Other foods include okra, beans, legumes, avocado, cauliflower, and citrus fruits.
Importance of Iron
The most important agent in managing sickle cell anemia is iron or Iron Phosphate (which is organic iron). Nature provides us with iron phosphate, which is needed for human hemoglobin.
One of the best ways to obtain optimal and maximum amounts of iron phosphate is via green vegetables and herbs.
Vegetables that are rich in iron include:
- Dark, leafy greens (i.e. spinach, arugula, kale, collard greens)
- Broccoli, Brussels sprouts
- Beans (esp. lima, black), lentils, chick peas, soybeans
- Artichokes
Other foods that are rich in iron include:
- Organic brown rice
- Organic eggs (specifically, the egg yolks)
- Pumpkin seeds, sunflower seeds
- Tahini (sesame butter)
- Tofu
- Dried fruit (prunes, raisins, peaches)
- Red meat
- Turkey or chicken giblets
- Liver
Note: If you eat iron-rich foods along with foods that provide plenty of vitamin C, your body can better absorb the iron.
Herbs that are rich in iron include:
- Thyme
- Yellow dock root
- Dandelion root
- Burdock root
- Nettle leaf
- Mullein leaf
- Devil's claw
- Iron weed
- Blue cohosh root
- Echinacea
- Red raspberry leaf
- Fenugreek
- White oak bark
You might also want to try these excellent blood purifiers:
- Red clover
- Strawberry leaf
- Chapparal
- Chickweed
- Manjistha
- Cayenne
- Elder berries
- Cerasee
- Oregon grape
Animal & Plant Sources of Iron
Animal sources of iron contain heme iron. Heme iron is absorbed better by your body than non-heme iron, the type of iron from plant foods.
Good sources of heme iron include beef, chicken, beef livers, turkey and fish. For example, a 3.5-oz. serving of cooked chicken liver provides 12.8 mg of iron and 3 oz. of beef tenderloin provides 3 mg of iron. A 3-oz. serving of tuna or chicken breast each contribute 1 mg of iron to your diet.
Fish such as sardines, anchovies, shellfish such as clams, mussels and oysters are high in iron.
Importance of Oxygen
Oxygen also plays a role in reversing iron deficiency disorders. Liquid oxygen drops products can prove most helpful in cases of sickle cell.
Taking daily alkaline baths (in sea salt) will help to alkalize the body. And if you have an oxygen or ozone machine, you can take an oxygen bath. If you add a whole box of sea salt to this bath, some serious healing will take place because now you're dealing with inundation of oxygen and alkalinity.
Minerals
Hematite cleanses the blood and stimulates the absorption of iron and the formation of healthy red blood cells, making it vital for persons battling sickle cell.
Malachite is ideal for sickle cell and iron deficiency anemia as it is an iron and also helps in absorbing copper. It consists of the blue-green dynamic (like blue-green algae) and therefore is a must for healing on all levels.
Dietary Intervention
Change your diet to one that's includes plenty of iron-rich foods. Natural sources of iron include:
- Parsley
- Spinach
- Greens (collards and mustard)
- Watercress
- Burdock
- Chard
- Kale
It is best to juice the above green foods (vegetables) or to eat them steamed (for seven minutes or less).
Seaweed
Seaweeds are also great sources of natural iron:
- Irish Moss
- Dulse
- Kelp
- Spirulina
- Chlorella
- Blue Green Algae
Seaweeds are the greatest food you can eat and are the most oxygenating plants on the planet and greatly increase and enhance oxygen throughout the body. But by all means, the best seaweed you can consume is Blue Green Algae.
Fruits
Fruits that provide good and moderate amounts of iron include:
- Black currants
- Grapes
- Cherries
- Strawberries
- Elder berries
- Blueberries
- Lycii berries
- Blackberries
- Pumpkin
- Lime
Grasses and Sprouts
Iron-rich grasses and sprouts are:
- Alfalfa
- Barley grass
- Wheat grass
ALFALFA (herb or sprouts) is laced with organic iron. Most commercial brands of chlorophyll are made from Alfalfa. So drink plenty of chlorophyll (adding it to your water).
BARLEY GRASS and WHEAT GRASS (2-4 ounces daily) also provide essential iron (and other minerals and nutrients) and are also great sources of chlorophyll.
Thiocyanate
Thiocyanate is known to have anti-sickling properties. Foods rich in Thiocyanate are:
- White yam
- Plantain
- Banana
- Pulse (all legumes)
- Butter beans
- Lentils
- Black eye peas
- Garbanzo beans (Chickpeas)
- Lima beans
- Millet
- Buckwheat
- Falafel
- Humus
- Oatmeal
- Teff (Injera)
- Turnips
- Rutabaga
- Brussel sprouts
- Almonds
- Raspberries
Foods to Avoid
More importantly, people with sickle cell should avoid processed foods and fast foods, including:
- Processed foods that contain refined flour, wheat, sugar, high fructose corn syrup, partially hydrogenated oil, gluten, preservatives.
- Starchy foods such as white potatoes, white rice, bread, pasta, corn.
- Foods that contain grain such as most cereals, breads, pastries; most bottled juices.
- Vegetable oils such as corn oil, soybean oil, canola oil.
Note: For a comprehensive list of the foods to avoid, go to this web page.
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