A: Only rarely do newborns have diabetes. Most people are surprised, however, to learn that diabetes can be recognized early in the second year of life in some children.

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Type 1 diabetes occurs in children frequently enough that one of its old names is "juvenile onset diabetes." There are two ages at which diabetes is most likely to be recognized around 4-5 years of age and during the early teen years. Type 1 diabetes can also be diagnosed later in life, even beyond age 50. People who have an older age of onset are often initially thought to have type 2 diabetes, but soon learn that they need insulin to control their blood glucose levels. Every year, we diagnose children under 2 years of age with type 1 diabetes. It is therefore important for parents who have children at high risk for diabetes to ask their pediatrician to test their child for diabetes if he or she develops symptoms of the condition excessive thirst and urination (usually an obvious change from the child's normal patterns) and weight loss, despite a good appetite.

Q: What is PANDA testing in my baby?

A: The PANDA study measures the inherited (genetic) tendency to develop diabetes. The tests will determine whether your baby has genes that tend to occur more frequently in people with diabetes than in people who do not have diabetes. If your baby does have high risk genes, it does not mean that he or she will eventually get diabetes. It just means the risk is higher for your baby than it is for the average child.

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Your child's first blood sample will be tested for diabetes risk genes that are called HLA genes. These genes control how immune responses develop and are some of the genes that are matched between donors and recipients for bone marrow transplants. HLA genes are a family of genes that lie close to one another on chromosome 6. The specific members of the HLA family that are examined in the PANDA study have rather boring names - DR and DQ. Everyone has a DR from their mother and another DR gene from their father. The same is true for DQ. There are many different versions of the DR and DQ genes and some of these versions put people at risk for getting type 1 diabetes. Other versions can actually protect people from the condition. The short names for the DR genes that are associated with diabetes are DR3 and DR4. The short names for the DQ genes that are associated with diabetes are DQ2 and DQ3. The children who are at highest risk of diabetes have inherited these high risk genes from both of their parents and those are the children who we will follow in PANDA. Other high risk genes for diabetes are being identified and we hope someday to include screening for these in PANDA.

A scientific discussion about the genetics of type 1 diabetes is available at http://www.uchsc.edu/misc/diabetes/eisenbook.html.

Q: What are the goals of PANDA?

* Learn how diabetes genes work to cause diabetes

* Discover the environmental factors that start beta cell autoimmunity

* Learn why the immune system does not stop autoimmune responses against beta cells

* Offer people with autoantibodies the chance to enter diabetes prevention trials.

Q: What are the different types of diabetes?

A: There are 3 common forms of diabetes in the US type 1, type 2, and gestational. Type 1 diabetes is the form of diabetes that is being studied in PANDA. It is caused by an abnormal reaction of the immune system that kills the cells that make the hormone called insulin. People who do not have enough insulin in their body have high blood glucose (sugar) levels and lose weight, because their body cannot properly use the nutrients in food. The only way to treat type 1 diabetes today is to replace the missing hormone, insulin. This has to be done by injection, because insulin pills are digested by the stomach before the insulin can be absorbed into the blood.

Type 2 diabetes is the most common form of diabetes in the US. It develops when two problems with insulin occur at the same time. The first problem is that the body resists normal insulin action. Therefore, more insulin than normal is needed to maintain normal body function. This insulin resistance is most frequently caused by being overweight. People with type 2 diabetes also have some deficiency of insulin production, but it is not as severe as in people with type 1 diabetes. Diet and exercise are the most important treatments for type 2 diabetes, but some people need pills or even insulin injections.

Gestational diabetes occurs in pregnant women and usually goes away after the baby is delivered. Occasionally, gestational diabetes may be the first sign of type 1 diabetes.

See more info here: http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/index.htm#2.

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Type 1 diabetes is known as an autoimmune disease. "Auto" means self, so autoimmune simply means an immune response against a part of yourself, in this case the beta cells in the Islets of Langerhans of the pancreas. The Islets of Langerhans are microscopic clusters of three important types of cells. Insulin is made by the beta cells in the islets and these beta cells are the targets of the autoimmune attack. The other two types of islet cells (alpha cells that make glucagon and PP cells that make pancreatic polypeptide) are not affected by the autoimmune attack. We do not know why the autoimmune attack starts, but we do know certain genes must be present and there are likely to be one or more triggers in the environment that start autoimmunity. Some of the proposed environmental triggers include viruses and certain foods. It is thought the environmental trigger is something to which we are all commonly exposed. It is only the people with the right gene mixture that actually get diabetes. Some people get a mild form of autoimmunity that does not progress all the way to full-blown diabetes.

We can detect autoimmunity against the pancreatic beta cells by a special test that measures immune cell products, called autoantibodies. Most people think of antibodies as important proteins that help our bodies fight infection. Autoantibodies are antibodies that react against parts of our own bodies. Insulin is one target of autoantibodies in some patients. Other targets of autoantibodies include beta cell proteins called glutamic acid decarboxylase (GAD) and IA-2 (also called ICA-512). Children in PANDA who have a high genetic risk for diabetes will be tested for these autoantibodies. If they are not present, it is unlikely (but not impossible) that they have an autoimmune response going on in their body. If they have one or more of these autoantibodies, it tells us that an autoimmune response against beta cells is either active at the time of the blood draw or has been active at sometime in the past. Autoantibodies can be detected months or even years before insulin deficiency becomes severe enough that blood glucose levels rise. Some people who develop autoantibodies never suffer enough damage to develop diabetes. A person who has autoantibodies against two or more different beta cell proteins (e.g. insulin and GAD) is more likely to get diabetes than a person who has autoantibodies against one beta cell protein.

http://www.uchsc.edu/misc/diabetes/eisenbook.html.

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Type 2 diabetes is a major public health threat in the US and has therefore become a major priority in health research and health care. There are over 17 million people in the US with type 2 diabetes and the numbers are rising every year. The major reason for this rise is the increased numbers of overweight and obese people in the US. Most overweight people do not have diabetes. They usually have some insulin resistance. Fortunately, their pancreas makes enough insulin to make up for the resistance. People who are overweight usually make more insulin than people who are not. Overweight people with diabetes usually have blood insulin levels that are closer to people of average weight and this is not enough to keep their blood glucose normal. As years pass, people with type 2 diabetes continue to lose the ability to make insulin and they often end up needing insulin injections eventually.

There is a very concerning rise in type 2 diabetes in US children. Between 1960-1980, the rate of type 2 diabetes was very low in kids, but it has been steadily increasing since then. It is likely that the children being affected today are the people who until now, developed diabetes much later in life. If these children are unable to control their diabetes well, they may end up getting some of the serious complications of the disease (e.g. heart attack, stroke, blindness, kidney failure) in their thirties or forties. Americans have to deal realistically with the severe consequences of their changing lifestyles. Higher amounts of food and high calorie drinks (e.g. fruit juice, soda) are being consumed in ever greater quantities and physical activity is being replaced in children by less active play (e.g. computer games, TV)

More information on type 2 diabetes is available at: http://www.learn-about-type-2-diabetes.com/

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Gestational diabetes occurs because resistance to insulin action is a normal part of pregnancy. Once the pregnancy is over, insulin action returns to normal and the high blood glucose levels go away. Gestational diabetes is a very important condition that needs careful treatment, because it causes many abnormalities in the baby, including large size, lung immaturity, low blood glucose, and low calcium.

Women who have diabetes before they get pregnant are not considered to have gestational diabetes, but their babies are at risk for the problems listed above and others. It is therefore very important that women with diabetes treat their disease very carefully when they are pregnant.

More information about the types of diabetes is available at http://www.nichd.nih.gov/publications/pubs/gest_diabetes.htm.

Q: PANDA is looking at my baby's DNA. Can PANDA investigators clone my baby?

A: NO! Despite claims made in the press, we do not have the technology to clone people. Although it may be possible in the future, PANDA investigators will never be allowed to clone your baby without specific permission from you and your child. We are not currently involved in any research that involves cloning animals or humans.

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The current method for cloning animals is to replace the nucleus of an ovum (egg) with the nucleus of a skin cell. Eggs normally have only one copy of each gene, so that when they combine with a sperm cell (which also has one copy of every gene), you end up with a single cell that contains two copies of every gene. Injection of the skin cell nucleus allows the altered egg a full allowance of 2 copies of each gene. You must use an ovum, because other cells do not have the ability to control the genes in a way that allows normal development of a baby. There is very little known about the long term effects of cloning and there is great concern about whether cloning is ethical.

It is possible that limited cloning will someday provide life saving treatments. For example, type 1 diabetes may someday be cured by cloning beta cells and transplanting those clones into a person.

A scientific discussion about cell therapy for diabetes is available at http://www.uchsc.edu/misc/diabetes/eisenbook.html.

Q: What is a gene?

A: Chromosomes are made of deoxyribonucleic acid (DNA). DNA in turn, contains areas called genes that tell our body how to make proteins. These proteins determine everything from the color of our hair to the way we fight an infection to the way we eliminate medicines from our body.

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A gene is a sequence of chemicals called nucleotides that tells a cell how to build a protein. There are 4 types of nucleotides adenine (A), guanine (G), cytosine (C), thymidine (T). Genes are organized in deoxyribonucleic acid (DNA) molecules and long strings of DNA are called chromosomes. Special enzymes use the DNA nucleotides as a template to make ribonucleic acid (RNA) and then RNA can be used by cells to make the protein encoded by the RNA.

The sequence of the nucleotides determines which proteins will be made by a cell and when the proteins will be made. The form of gene (allele) that increases the risk for type 1 diabetes contains almost the same sequence of nucleotides as the forms of that gene that do not increase the diabetes risk. A change of even one nucleotide can, however, make a major change in the type of protein that the cell makes from that gene. Even less obvious changes in proteins can change their function.

A detailed scientific discussion of the genetics of diabetes can be found at http://www.uchsc.edu/misc/diabetes/eisenbook.html.

Q: What is an insulin pump and who should use one?

A: Insulin can be injected continuously into people with diabetes with an insulin pump. The pumps are battery-operated devices that are about the size of a fold-up cell phone. A slow rate of insulin injection is provided by the pump all the time, and the rate can be increased at meal times to provide more insulin when it is needed most after eating.

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Current insulin pumps are not considered to be "artificial pancreases," because the person wearing the pump has to manually tell the pump how much insulin to provide at meal times. Many researchers are trying to invent a true artificial pancreas. A pump can help a person get better control of their diabetes, but it requires careful attention to blood glucose testing and food consumption. On the surface, pump therapy sounds as if it is easier than using needles and syringes to control diabetes. In fact, it takes more work and thought to do it properly. The payoff for this extra work is a lifestyle that more closely resembles one that a patient would follow if they did not have diabetes.

Commercially available pumps today are just beginning to electronically link the tasks of blood glucose testing and insulin injection. Computerized dose calculators help pump users calculate their doses of insulin. In the future, it is expected that pumps will include a sensor that continuously measures blood glucose and sends messages to the pump to respond appropriately. Internal pumps are devices that will be surgically implanted, so that no part of the pump will be visible. They are currently under investigation, but they are not available for commercial sale.

A detailed discussion about pumps can be found at www.childrenwithdiabetes.com.

Q: If I have a family member with diabetes, what is the risk that other relatives will develop type 1 diabetes?

A: In general, the risk that a person with a close family member with type 1 diabetes will themselves develop type 1 diabetes is about 5 percent (5 in 100). The risk in the general population is 0.3 percent (3 in 1000). The risk among relatives can be better defined by genetic and autoantibody testing.

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A child who has a father with diabetes has about a 6 per cent risk for developing diabetes, whereas a child who has a mother with diabetes has only a 2-3 per cent risk. The reason for this difference is being intensively researched. Both genetic and environmental reasons have been proposed, but nobody yet knows the true answer.

If a child has a brother or sister with diabetes, then the risk for the unaffected child of developing diabetes is about 5 per cent. If one identical twin has diabetes, the other twin has a risk of about 30-50 percent. The risk in non-identical twins is the same as it is for non-twins.

Genetic testing can improve the reliability of diabetes risk assessment. Imagine a case where the brother or sister of a child with diabetes has the same diabetes genes as their affected sibling. The risk for the unaffected child developing diabetes may be as high as 20-25 per cent. At the other extreme, an unaffected sibling may have inherited a protective gene that their sibling did not. This could result in a child who has almost no chance of getting diabetes.

Q: What are stem cells and what stem cell research is being done in diabetes?

A: Stem cells are immature cells that can replicate themselves and can develop into different kinds of cells as they mature. For instance, pancreatic islet cells can develop from cells that can also become liver cells. Some investigators claim to have found cells in the bone marrow that can develop into islet cells.

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Stem cell research is very controversial, because of the concern that single cells or small groups of cells could theoretically be used to create human beings. Such a goal is not possible with today's technology. It is hoped that stem cells can be purified from patients with organ failure, grown artificially into organs, and then transplanted back into the patient. This would avoid the need for anti-rejection drugs, since the transplanted organs would not be foreign to the transplant recipient.

Blood from the umbilical cord may be the best source of stem cells, so some investigators are examining the feasibility of massive cord blood banks. Preserved samples can be used for organ replacement later in life. Others hope that healthy organs can be used to derive stem cells from people after they develop an illness that requires treatment with organ replacement.

A detailed scientific discussion of the stem cell therapies can be found at http://www.uchsc.edu/misc/diabetes/eisenbook.html.

Q: Why don't all patients with diabetes get pancreas or islet transplants?

A: Transplantation is a potentially curative treatment for type 1 diabetes. The pancreas can be surgically removed from a donor and the whole organ can be transplanted into a recipient with diabetes. Another method is to chemically purify the islets from the rest of the pancreas and surgically inject the islets through a vein that runs to your umbilicus (belly button). The islets rest in the liver and function just like normal islets. Cadaveric donors (people who have died) must be used, because experience showed that living related donors put themselves at risk of getting diabetes if they donated half of their pancreas.

Whether a person receives a whole organ or islet transplant, they must take immunosuppressive drugs to prevent rejection of the transplanted tissue. These drugs can have serious side effects, such as infection or even cancer. Therefore, only people with diabetes who have life threatening problems are eligible for transplantation. Patients with diabetes that has caused severe kidney failure can require kidney transplantation. Immunosuppressive drugs are necessary in these people for the survival of the kidney, so they are eligible to receive a pancreas or islet transplant at the same time.

In addition to the concern about potentially harmful drugs, there is a shortage of donors for pancreases and islets. It is therefore important that people declare their desire to become organ donors, should an unexpected tragedy occur. Researchers are trying to create islets in the lab using genetic engineering or stem cells.

A detailed scientific discussion of the transplantation to cure diabetes can be found at http://www.uchsc.edu/misc/diabetes/eisenbook.html.

Q: How long will we remain in the PANDA study?

A: PANDA is a long term study and the success of our efforts depends on people remaining in the study until it is complete. We would like to follow your child until he or she has passed the age of highest risk for developing diabetes (after puberty is complete). Although we will do our best to limit any inconvenience to you, you can withdraw from the study any time you like.

Q: Can my extended family be studied in PANDA?

A: PANDA focuses on two groups of people at high risk for diabetes. One group consists of babies who prove to have high risk genes on the infant screening test. The other group is made of close relatives of people with diabetes. These include children, brothers, sisters, and parents of people with diabetes. We are happy to screen more distant relatives at the request of the family.

A: Why does one of my children require more frequent testing than the others?

A: The frequency of follow-up testing is determined by a child's risk for diabetes. Not all family members have the same risk. Our genetic and immune tests can identify children who are at a particularly high risk. These people are seen more frequently, some up to every 3 months.

Q: What should I do if I think my child has symptoms of diabetes?

A: If you have access to a blood glucose monitor and you know how to use it, you can measure his or her blood glucose and call the result in to your child's primary care physician or to our study physician. Normal blood glucose levels are below 100 mg/dL before eating breakfast and below 200 mg/dL after eating.

If you do not have a blood glucose meter and you think your child has been urinating and drinking frequently for a number of days, you should contact your primary care physician.

An extended discussion about the diagnosis of diabetes can be found at http://care.diabetesjournals.org/cgi/content/full/26/11/3160.

Q: Will the results of PANDA tests change my child's health insurance?

A: NO. By law, PANDA results should not have any effect on your child's health insurance. These tests are for research only and are considered protected information that your insurer is not entitled to review. The predictive tests tell us whether or not your child is probably going to get diabetes. They are not reliable enough to diagnose diabetes with certainty. To avoid confusion, it is wise to avoid having any information about PANDA on your child's hospital or doctors' medical charts.

Q: Can I do PANDA tests at my own doctor's office or clinic? Where else?

A: Perhaps. We try to make PANDA testing as easy as possible for you. We are happy to contact a local blood drawing facility (your Doctor's office or a nearby lab). If they are in agreement, blood can be drawn there and express shipped to us. We have an agreement with Quest Diagnostics Laboratories to draw blood at any of their laboratories. You can see if there is a Quest Diagnostics location near you by checking their website (www.questdiagnostics.com). Laboratory locations are provided under their "Patients and Consumers" section.

Any charges that arise because of these services will be covered by us, but please have us confirm the shipping procedure and payment schedule before getting your child's blood drawn. You can reach the PANDA office toll free at 1-888-225-7785.

Q: What does it cost to participate in PANDA?

A: The best part about PANDA is that it is FREE to you. We will pay for blood drawing and testing related to PANDA. Unfortunately, we cannot pay for tests that were ordered for other reasons, even if they are performed on the same blood sample as the one used for PANDA testing.

Q: How do I benefit from participating in PANDA?

A: There are no immediate benefits to you or your child, unless your child is one of the children who really goes on to get diabetes. Participation in studies like PANDA results in faster recognition of diabetes, when it does occur. This results in children being far less sick at the time the diagnosis is made. It usually prevents admission to an intensive care unit and it can, in some cases, be life-saving.

Perhaps of equal importance, participation in PANDA assures you the chance of participating in any trials of new treatments for diabetes prevention, should your child prove to be eligible.

Q: If my child is genetically at high risk, what are the chances that he or she will develop diabetes?

A: Both genetic factors and family history influence the chances of a child to develop type 1 diabetes (T1D). The chance for developing T1D is approximately 4-8% for a child with the high risk genes tested by PANDA when there is no family history and 10-25% when there is an immediate family member with T1D.

Q: If my child is genetically at high risk and has a positive autoantibody test, what are the chances that he or she will develop diabetes?

A: A positive autoantibody test will increase the chances for a child to develop T1D. The number of autoantibodies can influence the risk for the disease. The persistent presence of a single autoantibody will increase the risk to 25%-40%, while the persistent presence of multiple autoantibodies increases the risk to 50-80% over a five year period.

Q: PANDA has determined that my child is at high risk for diabetes. What can I do to prevent diabetes? Should I change their diet?

A: This is a very common and logical question. There is no known method for preventing type 1 diabetes. Restricting sugar or any other diet component has not been proven to prevent diabetes. We recommend you follow your primary care physician's dietary recommendations. Beware of cures or prevention treatments, especially those sold over the Internet. If you are interested in exploring prevention therapies, you can call the PANDA office 1-888-225-7785 or check the TrialNet website at the National Institutes of Health (NIH), http://www.diabetestrialnet.org/en/public/ . AU is affiliated with the University of Florida center.

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Diabetes prevention is the focus of a huge international research effort. Hundreds of millions of dollars are spent each year to reach this goal. Most treatments are aimed at altering the harmful immune response that kills the insulin-producing pancreatic beta cells. It is believed that treatments with minimal or no side effects may prevent diabetes if the treatment is started early enough (long before symptoms are obvious). The only way for you to have access to these potential treatments in the near future is to participate in research trials. For children who have entered later stages of diabetes, therapies that have a stronger effect on the immune system may be worthy of research trials. The drawback for these agents is that they usually have more potential for causing unwanted side effects. Ultimately, we may find that a combination of treatments can cure diabetes. For instance, a successful prevention therapy may be combined with a transplant treatment to cure disease in people who have developed symptoms of diabetes.