Genetic Information for Testing Type 1 Diabetes

GIFT-D

Developing and evaluating a theory-based web education and risk communication program for families with T1D

New Advanced Technology to Improve the Prediction and Prevention of Type 1 Diabetes

Massimo Trucco, P.I. - ImmunologyDenise Charron-Prochownik – Behavioral Science/ NursingJanice S. Dorman – Genetic EpidemiologyCathy Poole - TelemedicineLinda M. Siminerio – Diabetes Education/ NursingChristopher M. Ryan – PsychologyYvette Conley – Genetics in NursingPatti Schmitt – Project Director

Acknowledgement: Col. Dr. Ron Porapatich, M.D.US Army (TATRC)

Funded by the Department of Defense

Since the completion of the Human Genome Project and with rapid screening techniques available, problems arise when…….

• Prediction of disease is less than perfect• Disorder cannot be prevented/treated• Documentation of ‘genetic disorder’ may affect insurability and employability

• Knowing level of risk may cause psychological distress • People do not understand genetics (including health professionals)

• Is genetic testing for T1D unethical?

Genome Screens for T1DIDDM1 6p21 IDDM13 2q34-q35

IDDM2 11p15 IDDM15 6q21

IDDM3 15q26 IDDM17 10q25

IDDM4 11q13 IDDM18 5q31-q33

IDDM5 6q25-q27 1q42-qter

IDDM6 18q21 8q24

IDDM7 2q31 VDR, INFγ 12q12-qter

IDDM8 6q27-qter 16p11-p13

IDDM9 3q21-q25 16q22-q24

IDDM10 10p11-q11 17q24-qter

IDDM11 14q24-q31 TGFβ1 19p13-q13

IDDM12 2q33 Xp11

Intervention Trials for T1D

Study Intervention Target /Screen

TRIGR Avoid CM FDR / genetic

DIPP Insulin (N) GP / genetic

Trial Net Immunosuppr FDR / antibodies

and genetic

CM = cows milk, FDR = first degree relatives, CM = cows milk, FDR = first degree relatives, N = nasal, GP = general populationN = nasal, GP = general population

Natural History Studies for T1D• Conducted in the general population

• DAISY - Colorado• PANDA - Florida• DEW-IT - Washington

• Based on newborn genetic screening• Concerns about proper informed consent• Parents are notified of the results by mail• Newborns at ‘high’ risk (~6%) recruited for follow-up

Objectives of GIFT-D

Develop, implement, and evaluate appropriate education / communication programs about genetic testing and type 1 diabetes risk that can be widely disseminated to children, parents and health professionals

•

Education / Communication Programs• Programs developed for:

• Children (unaffected siblings in T1D families)• Parents (with an affected T1D child)• Health care professionals (for T1D)

• Covers basic genetics, concept of genetic susceptibility, the risk factors for T1D, and the risk and benefits knowing one’s genetic risk

• Decision aid to improve informed consent

• Focus is risk assessment and communication

Education / Communication ProgramsObjectives

• Increase knowledge• Improve risk perceptions• Clarify benefits and risks of genetic testing • Reduce barriers• Address ethical issues• Facilitate decision making• Prevent adverse reactions and minimize

distress

Genetic Testing for T1D

HLA-DQ screening by high throughput techniques

Develop an Algorithm to Estimate an Individual’s Risk

• Permits a more ‘personalized’ approach to risk estimation than those utilized by ongoing research projects

• Modeled after algorithm for breast cancer developed at the University of Pittsburgh

Photo of Risk Calculator

T1D Risk Algorithm

T1D ~42 yrs

• Based on regression analysis from genetic epidemiologic research conducted by our research group• Age• Family history of T1D• Sibling’s HLA-DQ genotype• Similarity of genotype with T1D proband’s genotype

• Translation research

T1D Risk Algorithm

A 12 year old child who shares both DQ haplotypes with her T1D sister has a ~7% chance of developing T1D by age 30 years if neither parent has T1D

Risk increases to ~38% if both parents have T1D

Your participation in the GIFT-D pilot study is very important to us because it will help improve our ability to predict risk for type 1 diabetes. As part of this study, we have calculated your chance of developing type 1 diabetes. Your personalized risk estimate for developing type 1 diabetes is currently _____%. This also means that you have a _____% chance of not developing the disease. Remember that this risk estimate does not give you a definite answer about whether or not you will develop type 1 diabetes. It helps predict your chance of getting the disease up to age 30. Your personalized risk estimate was calculated using the following factors: Your current age Your family history

Whether or not you have a brother or sister with type 1 diabetes Your genetic makeup

Whether or not you have forms of HLA genes associated with the disease Your risk is not based on any environmental risk factors such as viruses or diet. Important points about your risk for developing type 1 diabetes: The genetic component of your risk will not change because you cannot change what genes

you inherit. Genes are just one piece of the puzzle—environmental factors may also influence your risk. General information about type 1 diabetes: What is type 1 diabetes?

Insulin is a substance made by the pancreas that helps the body use the sugar from the food we eat for energy. Type 1 diabetes occurs when part of the pancreas stops doing its job and insulin is not available to help sugar enter the cells of the body.

What are the symptoms of type 1 diabetes? Symptoms may include: excessive thirst, frequent urination, extreme hunger, unusual weight loss, increased fatigue, blurry vision, irritability, and vomiting/nausea. If you have any of these symptoms, you should contact your doctor.

How is type 1 diabetes treated? Treatment involves daily blood sugar testing, careful dietary management, and daily insulin injections to help the body maintain the right amount of sugar in the blood.

If you have questions in the future about the GIFT-D pilot study or your personalized risk estimate, please call 412-624-7582.

Type 1 Diabetes Genes Environment

Theory-based Genetic Education and Risk Communication Program:

Development & Evaluation

Genetic Education ProgramBased on factors influencing behavior (genetic testing)

Expanded Health Belief Model

• Susceptibility• Severity• Benefit• Barrier• Self-efficacy• Intention

Hi! When you look in the mirror what do you see?Do you see a girl or a boy?Do you see eyes like your mom or dad?Do you have hair like a brother or sister?

We see something different.We see a person who might be a pioneer.You may have learned about pioneers in school who explore new lands.You may have heard about space pioneers who go into outer space.We are going to tell you about becoming a health pioneer.Just answer the questions as we go along!

A pioneer is someone who leads the way into the future.

Choose One:

Hi! When you look in the mirror what do you see?Do you see a girl or a boy?Do you see eyes like your mom or dad?Do you have hair like a brother or sister?

We see something different.We see a person who might be a pioneer.You may have learned about pioneers in school who explore new lands.You may have heard about space pioneers who go into outer space.We are going to tell you about becoming a health pioneer.Just answer the questions as we go along!

Absolutely right!Are you ready to be a pioneer?

A pioneer is someone who leads the way into the future.

You Chose:

Hi! When you look in the mirror what do you see?Do you see a girl or a boy?Do you see eyes like your mom or dad?Do you have hair like a brother or sister?

We see something different.We see a person who might be a pioneer.You may have learned about pioneers in school who explore new lands.You may have heard about space pioneers who go into outer space.We are going to tell you about becoming a health pioneer.

Just answer the questions as we go along!

You Chose:

NopeRemember, a pioneer is someone who does something before other people begin doing it. A pioneer is a leader.

A pioneer is someone who leads the way into the future.

You might be thinking,“How will they look inside my body? Maybe they will use a super x-ray machine! Maybe they have see-through body glasses that they will wear!”

In the future this might be one way, but we already have a way to see inside of you.

We might ask you to swish a little mouthwash to get a little spit. Do your parents use mouthwash for fresh breath? Or, we will take a soft brush and rub it on the inside of your cheek. It is safe, easy, quick and should not hurt at all! You should only have to do it once.

Rubbing a soft brush on the inside of my cheek is one way of getting information about how I am like my mom or dad.

Exactly right!Are you surprised that it is so simple?

You Chose:

Believe it or not, your spit is amazing! We can tell all sorts of things from spit! Right now, we want to discover one thing only. We want to see what your genetic chance is of getting a disease called type 1 diabetes. You know what a disease is – it is a problem with your health, like some people have problems breathing.A genetic chance – do you know what that means? To find out, let’s follow the trail of spit!

I will be tested to see what my chance is for getting all kinds of diseases.

Choose One:

First, your spit goes to the lab where it will be studied.Your spit is made up of very tiny cells. Cells are the building blocks of your body. The cell’s job is to tell the body what to do.

Cells are to your body like bricks are to a house.

Choose One:

We will get spit from lots of kids! That’s a lot of spit! After we study it, we won’t save your spit. It has already told us the special information we need.

You will save my spit and study it again in the future.

Choose One:

Half of your genes come from your mom, and half from your dad. Choose One:

If you say that I have a big chance of getting type 1 diabetes, then I will get it.

Exactly! A chance doesn’t mean anything is definite. Genes are only part of the puzzle.

Even if you have a big chance, that doesn’t mean that you will get it. Other things could change your chances too, like germs, or diet, or even things that we don’t know about yet. We cannot tell about everything from spit! We can only tell your genetic chance. We are just learning the different puzzle pieces.

You Chose:

It is interesting to learn about your genetic chance for getting type 1 diabetes. Kids who get type 1 diabetes can get sick. Their bodies cannot use the food they eat for energy. They need insulin to help their bodies get that energy. Their pancreas has stopped making insulin. The pancreas is an organ like your stomach.

In kids with type 1 diabetes, the pancreas has stopped working the way it should.

Choose One:

Only you, your parents, and a nurse or doctor will know your chance of getting type 1 diabetes. Before you share what you have learned about your chance with others, talk to your parents first.I should run and tell my best friend!

The answer is False.You should talk to a parent first.

You Chose:

Are you ready to be a health pioneer? If so, tell the nurse and get ready to give up some spit!

Soon, everyone will be tested for lots of different things. But for now, you would be one of the first

Because of pioneers like you, we are going to learn more about what causes type 1 diabetes. Our goal is to learn as much as we can, so that no one gets this disease in the future!

Thank-you! You have been great!

What are the risks of knowing the results of your

genetic test?

It may take some time to adjust to your test results.

Once you know your test results, you may• feel worried, angry, or sad;

• become concerned about getting a disease that may not develop;

• feel differently about yourself, your family, and your future;

• be upset to know that your risk is higher than the general population for a disease that cannot be prevented.

In rare cases, insurance companies or employers may treat people unfairly based on the results of genetic testing.

I have read and understand the risks of getting the results of my genetic test for type 1 diabetes.

Evaluation of Education Modules

• Outcome evaluation• Knowledge

• Psychosocial parameters

• Behaviors

2. Process evaluation• Time/effort

• Satisfaction

• Expectations

Measures• Knowledge

• Diabetes• Genetics• Inheritance of type 1 diabetes• Environmental risk factors

• Psychosocial parameters• Anxiety• Depression• Perceived risk• Health beliefs / intention• Health quality of life• Stigma / discrimination

(insurance / employment)• Family Function

• Behaviors• Receives genetic testing• Receives counseling• Prevention behavior changes (health

and/or lifestyle related)• (e.g. diet, seeks prevention tx) @ 1

month and 3 years• Seeks other information on the web-

based resource• Disclosure

• Process evaluation• Time / effort• Satisfaction• Expectations(Control: Optimism, Religiosity, Life

Events...)

Develop Web-Based Format for Education & Communication Programs

• Broaden reach• Flexibility• Easy to use• Capture data online• Coordinated all components of the project

Genetic Education for Health Care Professionals

Three Web-based modules:

1. Basic genetic concepts

2. Genetics of diabetes

3. Counseling issues

Continuing education online