The faculty and staff at Riley Hospital for Children at Indiana University Health are engaged in a number of research projects which will lead to improved health for children with diabetes and their families.

Type 1 Diabetes

What is type 1 diabetes?

Type 1 diabetes (T1D) is a life-long disease that typically occurs in children but can develop in adults. It occurs when the body attacks and destroys the insulin-producing cells in the pancreas. Destruction of the cells is gradual and most symptoms of diabetes do not begin until the majority of the insulin-producing cells are destroyed. Most people do not realize they are developing diabetes until there has been extensive loss of the insulin producing cells.

Current Clinical Studies

Type 1 Diabetes TrialNet

Type 1 Diabetes TrialNet is an international network of clinical centers dedicated to conducting research to prevent type 1 diabetes in those at risk for the disease and also to discover therapies that will preserve the body's capacity to produce insulin in those that are recently diagnosed with the disease. TrialNet researchers are experts in both diabetes and the body's immune system.

TrialNet is conducting three types of research:

  • Pathway to Prevention Studies: to learn more about risk factors associated with the development of type 1 diabetes.
  • Diabetes Intervention Studies: to test therapies that may preserve insulin secretion in people recently diagnosed with type 1 diabetes.
  • Diabetes Prevention Studies: to test therapies that may delay or prevent the onset of type 1 diabetes.

Natural History Studies
Our goal is to further knowledge about risk factors in individuals at risk for developing Type 1 Diabetes. We are studying close relatives of people with Type 1 Diabetes. Relatives of people with Type 1 Diabetes have a 10 – 15 times greater risk for the disease than people with no family history. Therefore, TrialNet is screening first and second-degree relatives of people with this type of diabetes. A screening test is done first to see if specific autoantibodies are present in the blood. Autoantibodies are proteins made by the immune system which indicate a greater risk for developing Type 1 Diabetes. These autoantibodies include ICA, GAD65, IAA and ICA512, and are a sign that the immune system may be attacking the insulin-producing cells in the pancreas. About four percent of family members of people with Type 1 Diabetes have autoantibodies. To do the test, a small sample of blood is drawn from the arm. To participate in the Screening Phase, individuals must be:

  • 45 years of age or younger and have a brother, sister, child, or parent with Type 1 diabetes, or
  • 20 years of age or younger and have a cousin, aunt, uncle, niece, nephew, half sibling, or grandparent with Type 1 diabetes

Children less than one year old are not eligible to be screened.

Note: Someone probably has Type 1 Diabetes if he/she:

  • Developed diabetes before age 40 years of age AND
  • Started taking insulin injections within a year of diagnosis

Individuals who are found to be autoantibody-positive will be offered the opportunity to have additional tests that will allow more precise estimation of their chances of developing type 1 diabetes. In addition to having the opportunity to be enrolled in the surveillance component of the Natural History Study, qualifying individuals may be eligible for enrollment in Prevention Studies. All research volunteers will be closely monitored for early detection of type 1 diabetes. Early detection of type 1 diabetes may improve blood sugar control and reduce the chances of developing complications. In addition, study participation may help other people at risk for type 1 diabetes.

Diabetes Prevention Studies
These studies are designed to determine whether new therapies can delay or prevent the onset of type 1 diabetes in “at risk” individuals. If the therapy being tested is successful, the development of diabetes maybe delayed or prevented in those participating. (Note: Eligibility criteria will vary for different diabetes prevention studies)

Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Study
The purpose of the TrialNet Oral Insulin Trial is to determine whether repeated treatment with oral (by mouth) human insulin, will prevent or delay the development of Type 1 Diabetes (T1D) in non-diabetic relatives of patients with T1D who are positive for insulin autoantibodies but who do not have elevated blood sugars.  Subjects will be randomized to receive oral insulin or a placebo (inactive substance). Recruitment and initial screening to identify subjects will be done through the TrialNet Natural History Study of the Development of Type 1 Diabetes study. As part of this study, subjects will have additional testing, and if eligible and willing, will be entered into the Oral Insulin trial. Eligible subjects are non-diabetic relatives of patients with T1D, who have normal blood sugars in response to an oral glucose tolerance test (OGTT) and who are confirmed to be positive for antibodies to insulin and as well as other diabetes autoantibodies.

The primary outcome of this study is the time from study entry to the development of diabetes as defined by the American Diabetes Association (ADA).
Secondary objectives include the description of the effects of treatment with oral insulin compared to placebo on other indicators of diabetes risk. Secondary objectives also include the assessment of the effects of treatment on the immune system and blood sugar control, and the association of these markers with the risk of diabetes risk factors.

Inclusion Criteria

  • Have a relative with T1D
  • If the relative is a sibling or a child, the study participant must be 3 – 45 years of age. If the relative is a second or third degree relative (i.e. niece, nephew, aunt, uncle, grandchild, cousin), the study participant must be 3 – 20 years of age
  • Willing to sign the Informed Consent Form
  • An oral glucose tolerance test performed within seven weeks prior to randomization in which:  fasting plasma glucose < 110 mg/dL, and two hour plasma glucose < 140 mg/dL
  • Insulin autoantibody confirmed positive within the previous six months
  • Two samples with at least one autoantibody other than the insulin autoantibody within the previous six months

Exclusion Criteria

  • Does not meet the above conditions. Subjects who are insulin autoantibody positive but have no other autoantibodies are not eligible
  • Has severe active disease, e.g. chronic active hepatitis, severe cardiac, pulmonary, renal, hepatic, immune deficiency and/or disease that is likely to limit life expectancy or lead to therapies such as immunosuppression during the time of the study
  • Prior participation in a trial for prevention of T1D
  • History of treatment with insulin or other drug to lower blood sugar
  • History of therapy with immunosuppressive drugs or steroids within the past two years for a period of more than three months
  • Ongoing use of medications known to affect blood sugar such as: sulfonylureas, growth hormone, metformin, anti-seizure drugs, diuretics, niacin, or certain drugs used to treat high blood pressure. Subjects on such medications should be changed to a suitable alternative, if available, and will become eligible one month after medication is discontinued
  • Pregnant or intends to become pregnant while in the study or breast feeding
  • Unable to follow study instructions
  • An abnormal glucose tolerance test
  • Subject has genetic markers associated with a lowered risk for type 1 diabetes

Anti-CD3 mAb (Teplizumab) for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

The purpose of this study is to see if an experimental medication called teplizumab may stop or slow down the autoimmune process destroying beta cells in people who are of high risk for developing type 1 diabetes. Beta cells make insulin, and their destruction starts years before the person shows any symptoms of diabetes. In this study, we will compare people who get infusions of teplizumab with those who get infusions that look the same but have no teplizumab, called a placebo. The infusions are every day for 14 days and neither the participant nor the study team knows during the time of infusions which is being given. After the infusion visits, participants return for five more study visits in the first year, and every six months after the first year. Persons can be screened for the Teplizumab study if they are identified as eligible after participating in the TrialNet Natural History Study. As part of this study, subjects will have additional testing, and if eligible and willing, will be entered into the Teplizumab study.

Eligible subjects are non-diabetic relatives of patients with T1DM who have impaired blood sugars in response to an oral glucose tolerance testing (OGTT) and who are confirmed to be positive for diabetes autoantibodies.

The primary outcome of this study is the time from study entry to the development of diabetes as defined by the American Diabetes Association (ADA). Secondary objectives include the description of the effects of treatment with teplizumab compared to placebo in other indicators of diabetes risk. Secondary objectives also include the assessment of the effects of treatment on the immune system and blood sugar control, and the association of these markers with the risk of diabetes risk factors.

Intervention Studies in Newly-Diagnosed Diabetes

It is thought that 10 – 15 percent of the normal number of insulin-producing beta cells remain in the pancreas at the time that someone is diagnosed with diabetes. The ability to produce insulin, even quantities that are not able to bring blood sugars into the normal range, has been shown to decrease serious low blood sugars (hypoglycemic events) and the long-term complications of diabetes.

  • The goal of these research studies is to preserve insulin secretion in people newly diagnosed with type 1 diabetes.
  • Eligible participants will be randomly (like the flip of a coin) put in either an experimental treatment group or a control group. The experimental group will receive the new treatment while the control group will receive a "pretend" treatment. This how researchers know if the experimental treatment is successful.

Type 1 Diabetes Exchange Registry 

The Type 1 Diabetes (T1D) Exchange is designed to gather data on patients who have type 1 diabetes. The exchange aims to have 100,000 members and a network of over 60 clinical centers within three years. The primary goal of the T1D Exchange Registry is to advance the understanding of type 1 diabetes and to identify promising new treatments, technologies and solutions for patients. At clinic appointments, participating individuals complete yearly questionnaires that include diabetes care, insulin management, and family history. A $20 amazon.com gift certificate will be provided after the initial enrollment.

To be eligible you must:

  • Have type 1 diabetes
  • Currently be using insulin to manage your diabetes
  • Age range of birth to 99 years old

Long Term Insulin Pump Therapy in Very Young Children with Diabetes 

  • Investigations of clinical, brain function, behavioral, academic achievement, and quality of life measures in 20 children aged 6 – 10 years diagnosed with diabetes for greater than five years who have received long-term insulin pump therapy (greater than three years) compared to children matched for age, sex, average blood sugars, and diabetes duration treated with insulin injections.
  • Assessments of blood sugar outcomes, cognitive outcomes, parenting stress, and diet changes in 40 children with diabetes under five years of age prior to and 12 months after the implementation of insulin pump therapy.
  • Investigations of clinical, brain function, behavioral, academic achievement, and quality of life measures in 20 children aged 6 – 10 years diagnosed with diabetes for greater than five years who have received long-term insulin pump therapy (greater than three years) compared to children matched for age, sex, average blood sugars, and diabetes duration treated with insulin injections.
  • Assessments of blood sugar outcomes, cognitive outcomes, parenting stress, and diet changes in 40 children with diabetes under five years of age prior to and 12 months after the implementation of insulin pump therapy.
  • Analysis of our clinic population utilizing pumps, collecting outcomes data on: clinical variables, predictors of long-term 'success' in blood sugar control, quality of life, and autonomy in diabetes management.

Current Basic Science Diabetes Research

In addition to the clinical studies, Riley researchers are also at the forefront of the basic research studies that will form tomorrow’s treatments and cures for type 1 diabetes. Currently, there are six basic science researchers who collectively employ over 30 scientists. These scientists use cell and animal models of type 1 diabetes to understand the causes of the disease and to find new avenues to treat or cure altogether. These researchers are the only ones in the entire state of Indiana to receive funds for this research by the Juvenile Diabetes Research Foundation and the American Diabetes Association, in addition to the National Institutes of Health. The areas of research include:

  • The autoimmune response of type 1 diabetes and how to halt it
  • Ways to protect the insulin producing cells from destruction by the immune system
  • Drugs to improve the way insulin works
  • Ways to enhance insulin release
  • Using stem cells to make new insulin producing cells

For More Information

For more information contact the Principal Investigator Linda DiMeglio MD, MPH or the study coordinator; Maria Spall RN, CCRP at 866.230.8486 or 317.948.8879.