Posted by Ellen on October 31, 2001 at 19:54:37:
Large-Scale Diabetes Study Planned
New York City, October 31, 2001 — On October 25-26, 2001, leading diabetes scientists gathered outside Washington, DC, to discuss the current state of research in epidemiology — an important area of medical research — and to offer advice to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) on organizing and funding a large-scale study of the disease. Four members of JDRF’s research staff attended “Etiology and Epidemiology of Early Autoimmune Type 1 Diabetes in Humans” in Alexandria, Virginia, along with diabetes researchers and experts in such scientific fields as epidemiology, virology, immunology, imaging and biostatistics.
Epidemiology is the branch of science that studies the frequency and patterns of diseases in populations — whole countries or defined areas or subgroups — and identifies the factors — genetic, immunological, environmental — that may cause these patterns. Population studies have contributed significantly to our understanding of diabetes and have helped form public health planning in the United States and around the world.
The NIDDK, a part of the National Institutes of Health (NIH), was seeking guidance from the attendees as it prepared to issue a new Request for Applications (RFA), encouraging researchers to take part in a broad effort to collect and analyze data from large groups of people both with Type 1 diabetes and at risk for developing the disease. The meeting included presentations on what is known about the disease’s early stages and the genetic, environmental and immunologic aspects that may be contributing to the affliction.
NIDDK wanted input on what had been learned from diabetes studies already under way. Many of the studies discussed were funded wholly or in part by JDRF, including the, Diabetes Prediction and Prevention Project (DIPP)(NIDDK) , the Prospective Assessment in Newborns for Diabetes Autoimmunity (PANDA), and the Diabetes Prevention Trial—Type 1 (DPT-1).
Epidemiology is an imperfect science, depending more on observation and hypothesis than on formal proof, and studies in this field often fail to provide definitive answers. Nonetheless, epidemiological studies play a critical role in determining how diabetes and autoimmune destruction of beta cells begin. There was general agreement at the meeting concerning the best approach for NIDDK to take in funding an ambitious, wide-ranging project:
Research should be encouraged and funded that analyzes data already gathered for existing population studies in the U.S and abroad. Given its considerable funding capacity, NIDDK clearly is in the best position to oversee a large consortium consisting of smaller projects designed to answer specific questions or gather certain types of data.
In addition, a new prospective study should be launched collecting samples and data from subjects beginning at a very young age and continuing for at least five years. The new prospective study should have two main arms—one focusing on the general population and one concentrating on people judged to be at high risk for developing the disease. The general population study might include as many as 100,000 subjects, while the high-risk component would focus on close relatives of those with diabetes and enroll a much smaller number—possibly around 5,000.
Each study should collect as much data and samples as is reasonable because the material may prove of use in other studies, either ongoing or in the future. A tissue bank that would store and preserve samples for study would be best overseen and operated by NIH, both to make possible widespread access and to ease concerns of Institutional Review Boards at participating facilities.
The genes at the human leukocyte antigen (HLA) locus identify genetic risk for Type 1 diabetes. The alleles (alternate forms of a gene at a given locus) that identify high-risk, medium-risk and protection from Type 1 diabetes are known. Although these genes do not predict disease development, all epidemiological studies should employ the tests that identify these high-risk patients and then proceed to aggressive follow-up.
The “early warning” sign for which many researchers test to detect diabetes risk is the presence of multiple autoantibodies suggesting the immune system may be attacking the body’s pancreatic islet cells. Autoantibodies are the best measure currently available, but there is no clear relation between their presence and islet function. Researchers need to find a more direct measure that islet function is actually deteriorating. Measuring beta cell mass might be an improvement, if the relationship between mass and function could be clarified.
A high priority should continue to be placed on developing a standardized T-cell assay, which would detect presence of those immune cells specifically targeting pancreatic beta cells. (Autoantibodies are made by the immune system’s B cells.)
Data needs to be collected and organized in a standardized way so that it can be shared across projects. Researchers must agree on criteria for data categories. (For example, minimum level of antibody in order to be categorized as “antibody positive”).
Incentives should be offered to encourage participants to remain in a study for the duration needed for the research. Dropouts that occur as a trial progresses can undermine research efforts. Researchers also need to consider the ethical issues of testing for disease probabilities and how it may impact the lives of those participating.
NIDDK is expected to announce and post its RFA very soon. JDRF will continue working with NIH and other funding bodies to promote research in this area. NIH and NIDDK funding opportunities are posted on their Web sites. Read about other recent JDRF-funded genetic studies.