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Thursday, June 18th, 2009 | Author: admin

You’ve probably wondered how you got diabetes. You may worry that your children will get it too.

Unlike some traits, diabetes does not seem to be inherited in a simple pattern. Yet clearly, some people are born more likely to get diabetes than others.

What leads to diabetes?

Type 1 and type 2 diabetes have different causes.  Yet two factors are important in both.  First, you must inherit a predisposition to the disease. Second, something in your environment must trigger diabetes.

Genes alone are not enough.  One proof of this is identical twins.  Identical twins have identical genes.  Yet when one twin has type 1 diabetes, the other gets the disease at most only half the time.  When one twin has type 2 diabetes, the other’s risk is at most 3 in 4.

Type 1 diabetes

In most cases of type 1 diabetes, people need to inherit risk factors from both parents.  We think these factors must be more common in whites because whites have the highest rate of type 1 diabetes.  Because most people who are at risk do not get diabetes, researchers want to find out what the environmental triggers are.

One trigger might be related to cold weather.  Type 1 diabetes develops more often in winter than summer and is more common in places with cold climates.  Another trigger might be viruses.  Perhaps a virus that has only mild effects on most people triggers type 1 diabetes in others.

Early diet may also play a role.  Type 1 diabetes is less common in people who were breastfed and in those who first ate solid foods at later ages.

In many people, the development of type 1 diabetes seems to take many years.  In experiments that followed relatives of people with type 1 diabetes, researchers found that most of those who later got diabetes had certain autoantibodies in their blood for years before.

(Antibodies are proteins that destroy bacteria or viruses.  Autoantibodies are antibodies ‘gone bad,’ which attack the body’s own tissues.)

Type 2 diabetes

Type 2 diabetes has a stronger genetic basis than type 1, yet it also depends more on environmental factors.  Sound confusing?  What happens is that a family history of type 2 diabetes is one of the strongest risk factors for getting the disease but it only seems to matter in people living a Western lifestyle.

Americans and Europeans eat too much fat and too little carbohydrate and fiber, and they get too little exercise.  Type 2 diabetes is common in people with these habits.  The ethnic groups in the United States with the highest risk are African Americans, Mexican Americans, and Pima Indians.

In contrast, people who live in areas that have not become Westernized tend not to get type 2 diabetes, no matter how high their genetic risk.

Obesity is a strong risk factor for type 2 diabetes.  Obesity is most risky for young people and for people who have been obese for a long time.

Gestational diabetes is more of a puzzle.  Women who get diabetes while they are pregnant are more likely to have a family history of diabetes, especially on their mothers’ side.  But as in other forms of diabetes, nongenetic factors play a role.  Older mothers and overweight women are more likely to get gestational diabetes.

Type 1 diabetes: your child’s risk

In general, if you are a man with type 1 diabetes, the odds of your child getting diabetes are 1 in 17.  If you are a woman with type 1 diabetes and your child was born before you were 25, your child’s risk is 1 in 25; if your child was born after you turned 25, your child’s risk is 1 in 100.

Your child’s risk is doubled if you developed diabetes before age 11.  If both you and your partner have type 1 diabetes, the risk is between 1 in 10 and 1 in 4.

There is an exception to these numbers.  About 1 in every 7 people with type 1 diabetes has a condition called type 2 polyglandular autoimmune syndrome.

In addition to having diabetes, these people also have thyroid disease and a poorly working adrenal gland.  Some also have other immune system disorders. If you have this syndrome, your child’s risk of getting the syndrome including type 1 diabetes is 1 in 2.

Researchers are learning how to predict a person’s odds of getting diabetes.  For example, most whites with type 1 diabetes have genes called HLA-DR3 or HLA-DR4.

If you and your child are white and share these genes, your child’s risk is higher.  (Suspect genes in other ethnic groups are less well studied. The HLA-DR7 gene may put African Americans at risk, and the HLA-DR9 gene may put Japanese at risk.)

Other tests can also make your child’s risk clearer.  A special test that tells how the body responds to glucose can tell which school-aged children are most at risk.

Another more expensive test can be done for children who have siblings with type 1 diabetes.  This test measures antibodies to insulin, to islet cells in the pancreas, or to an enzyme called glutamic acid decarboxylase.  High levels can indicate that a child has a higher risk of developing type 1 diabetes.

Type 2 diabetes: your child’s risk

Type 2 diabetes runs in families.  In part, this tendency is due to children learning bad habits eating a poor diet, not exercising–from their parents.  But there is also a genetic basis.

In general, if you have type 2 diabetes, the risk of your child getting diabetes is 1 in 7 if you were diagnosed before age 50 and 1 in 13 if you were diagnosed after age 50.

Some scientists believe that a child’s risk is greater when the parent with type 2 diabetes is the mother.  If both you and your partner have type 2 diabetes, your child’s risk is about 1 in 2.

People with certain rare types of type 2 diabetes have different risks.  If you have the rare form called maturity-onset diabetes of the young (MODY), your child has almost a 1-in-2 chance of getting it, too.

More Information on Genetics

If you would like to learn more about the genetics of all forms of diabetes, the National Institutes of Health has recently published The Genetic Landscape of Diabetes.  This free online book provides an overview of the current knowledge about the genetics of type 1 and type 2 diabetes, as well other less common forms of diabetes.  The book is written for health professionals and for people with diabetes interested in learning more about the disease.

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Thursday, June 18th, 2009 | Author: admin

Over 18 million Americans have diabetes; of these, about 5 million do not know they have the disease (1).

Type 1 diabetes accounts for 5-10% of cases, affecting 1 of 400 children and adolescents.

Type 2 diabetes is extremely common, accounting for 90-95% of all cases of diabetes. This form of diabetes can go undiagnosed for many years, but the number of cases that are being diagnosed is rising rapidly, leading to reports of a diabetes epidemic.top link

The Type 2 Diabetes Epidemic

When people think of epidemics, they often think of infectious diseases such as SARS, HIV, or the flu. However, the prevalence of type 2 diabetes is now at epidemic proportions. In the United States, diabetes accounts for over 130 billion dollars of health care costs and is the fifth leading cause of death ( 2). The number of new cases being diagnosed continues to rise. It has been estimated that of the children born in the year 2000, 1 of 3 will suffer from diabetes at some point in their lifetime ( 3). Diabetes is predicted to become one of the most common diseases in the world within a couple of decades, affecting at least half a billion people ( 4).


Estimate your risk of developing Type 2 Diabetes

In the past, type 2 was rarely seen in the young, hence its original name of “adult-onset diabetes”. But now type 2 diabetes is increasingly being diagnosed in young adults and even in children. In Japan, more children suffer from type 2 than type 1 (“juvenile onset”) diabetes. This young generation of diabetics will have many decades in which to develop the complications of diabetes.

In 1990, 4.9% of the American population were diagnosed with diabetes (see Flash Animation 1). This increased to 7.9% by the year 2001 ( 5).top link

Obesity

The driving force behind the high prevalence of diabetes is the rise of obesity in the population. In today’s society, it can be difficult to maintain a healthy weight. We have the combination of ample food and a sedentary lifestyle. This is in stark contrast to only a couple of hundred years ago, when people were more active and food supplies were not as abundant. As a result, many of us are heavier than we should be.


Calculate your ideal weight

Being overweight or obese is defined by a calculation called the Body Mass Index (BMI). It is a calculation that takes your height and weight into consideration and gives you a score. A score of 18–24.9 is a healthy weight. If you are overweight, your score lies within the range to 25–29.9; a score of 30 and above indicates obesity.


Calculate your BMI

In 1991, it was estimated that 12% of the population were obese ( 5). By the year 2001, this had increased to an estimated 20.9% of the population; this represents over 44 million obese adult Americans. A more recent study estimated that a record 30% of the American population are now obese ( 6) (see Flash Animation 2).

Obesity is a major problem for the United states. Every year, an estimated 300,000 US adults die of causes related to obesity ( 7). Obesity is also a huge economic burden, accounting for up to 4% of healthcare costs in the United States ( 8).top link

Thrifty Genes

Epidemics of infectious diseases increase when there is increased spread of the infectious agent and decrease when the number of victims who are susceptible falls (they either become immune or they die). An epidemic of a genetic disease such as type 2 diabetes is similar. The number of cases rises when there is a rise in environmental risk (abundant food supplies, lack of activity) and decreases when the number of susceptible individuals falls (by deaths from the complications of diabetes).

The classic example of an epidemic of diabetes is found on an remote island in the Pacific Ocean, the island of Nauru. Before the turn of the 20th century, the lifestyle of Nauruans was harsh. The soil was poor, agriculture was difficult, and frequent episodes of starvation were common. Despite these adverse conditions, the islanders were noted to be “heavy”. In 1922, it was discovered that Nauru contained phosphate rock, which was then mined for use in fertilizer, and for which the islanders received royalties. Over several decades, the Nauruans became extremely wealthy, and with their new-found riches came major lifestyle changes. Food was now abundant and could be bought from stores. Instead of fishing and farming, Nauruans now led sedentary lives. By the 1950s, type 2 diabetes exploded from being non-existent in this population to affecting 2 of 3 adults over the age of 55 and becoming a common cause of death.

The case of the Nauruans is an extreme case of how type 2 diabetes can rapidly reach epidemic proportions, and “thrifty genes” may be involved. It has been postulated by Neel ( 9) that genes that are metabolically thrifty give a survival advantage in times when there is a constant threat of famine and starvation. When food is abundant, these genes aid the efficient metabolism of the food, enabling rapid build up of fat stores. This enabled people like the Nauruans to survive food shortages later on. But when food is always abundant, a thrifty genetic makeup turns into a survival disadvantage. Thrifty genes cause obesity, which in turn predisposes to diabetes. The epidemic that took hold of the island of Nauru is now emerging in developing countries and already has a firm hold on the developed world.top link

References
1. National Diabetes Statistics . National Diabetes Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

2. Hogan P, Dall T, Nikolov P. Economic costs of diabetes in the US in 2002. Diabetes Care 2003; 26(3):917-932. (PubMed)

3. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. JAMA 2003; 290(14):1884-1890. (PubMed)

4. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21(9):1414-1431. (PubMed)

5. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2001; 289(1):76-79. (PubMed)

6. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA 2002; 288(14):1723-1727. (PubMed)

7. Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual deaths attributable to obesity in the United States. JAMA 1999; 282(16):1530-1538. (PubMed)

8. Allison DB, Zannolli R, Narayan KM. The direct health care costs of obesity in the United States. Am J Public Health 1999; 89(8):1194-1199. (PubMed)

9. Neel JV. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? JAMA 1962; 14:353-362. (PubMed)

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Thursday, June 18th, 2009 | Author: admin
Preface

PDF Document 1. Introduction to Diabetes
Created: July 7, 2004
Classification

History of Diabetes

Epidemiology

Physiology and Biochemistry of Sugar Regulation

The Story of Insulin

PDF Document 2. Genetic Factors in Type 1 Diabetes
Created: July 7, 2004
IDDM1 Contains the HLA Genes

IDDM2 Contains the Insulin Gene (INS)

Other Type 1 Diabetes Susceptibility Loci: IDDM3–IDDM18

An Inhibitor of the Immune Response (CTLA4)

PDF Document 3. Genetic Factors in Type 2 Diabetes
Created: July 7, 2004
The Sulfonylurea Receptor (ABCC8)

The Calpain 10 Enzyme (CAPN10)

The Glucagon Receptor (GCGR)

The Enzyme Glucokinase (GCK)

The Glucose Transporter GLUT2

The Transcription Factor HNF4A

The Insulin Hormone (INS)

The Insulin Receptor (INSR)

The Potassium Channel KCNJ11

The Enzyme Lipoprotein Lipase (LPL)

The Transcription Factor PPARG

The Regulatory Subunit of a Phosphorylating Enzyme (PIK3R1)

PDF Document 4. Other Types of Diabetes
Created: July 7, 2004
Genetic Defects of Beta Cell Function (MODY and Others)

MODY1: Caused by a Mutation in Transcription Factor HNF4A

MODY2: Caused by a Mutation in the Enzyme Glucokinase (GCK)

MODY3: Caused by a Mutation in Transcription Factor TCF1

MODY4: Caused by a Mutation in Transcription Factor IPF1

MODY5: Caused by a Mutation in Transcription Factor TCF2

MODY6: Caused by a Mutation in Transcription Factor NEUROD1

Genetic Defects in Insulin Action

Diseases in the Exocrine Pancreas

Diseases of the Endocrine System

Drug- or Chemical-induced Diabetes

Infections

Uncommon Forms of Immune-mediated Diabetes

Other Genetic Syndromes Sometimes Associated with Diabetes

PDF Document 5. Gestational Diabetes
Created: July 7, 2004
NIH Lectures
The Genetic Landscape of Diabetes

Preface

"The Genetic Landscape of Diabetes" is a guide to the variations in our DNA that may influence our risk of developing diabetes.

It is well known that a lifestyle of inactivity and excessive food intake plays an important part in diabetes risk. But diabetes is a genetic disease as well as a disease of lifestyle. Rare forms of diabetes are caused by a single gene mutation, but in most cases of diabetes, many genes are thought to be involved, together forming a "genetic risk".

Who should read this book?

Readers with an interest in science, patients with diabetes, physicians, high school students, and research scientists.

For patients and students, summaries provide outlines of the roles of genes, and background information introduces scientific information in a gradual way.

Research scientists and geneticists may be interested to read the "Molecular Information" for each gene. Here the book showcases the power and utility of NCBI tools for biomedical research. These tools include a gene "catalog" (Entrez Gene), the gene location (Map Viewer), searching for similar genes in other species (BLAST), and the latest research findings (PubMed and OMIM).

Why should you read this book?

"The Genetic Landscape of Diabetes" introduces the reader to what diabetes is—from its discovery thousands of years ago to our modern-day understanding of how this disease, characterized by high blood sugar, develops.

The first chapter provides calculators that help you calculate your ideal body weight and BMI. Animated maps of the United States show the rise in obesity and diabetes.

Other chapters guide the reader through the genetic variations that may play roles in type 1 diabetes, type 2 diabetes, and other types. The genes discussed encode proteins that have diverse functions in cells—from transcription factors that influence the expression of other genes, to ion channels that control the release of insulin, from transporters that pump glucose into cells, to enzymes that speed up the break down of glucose.

The book closes with "NIH lectures"—videos of some of the most recent lectures given by researchers who have been invited to the NIH to discuss obesity and diabetes.

What makes this book unique?

The genetics of diabetes is complicated—but this book is not and is written for a wide audience. Because what we know about the genetics of diabetes is continually changing, links to live searches of the latest published literature and data will keep this book up to date. All of the content (the online book and the PDFs) is free.

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