The best way to attack type 1 diabetes is to stop it before it ever starts, but this requires sophisticated knowledge of the underlying causes of disease. Ground breaking NIH efforts (T1DGC, TEDDY, TRIGR) to identify the genes responsible for susceptibility to type 1 diabetes coupled with the identification of environmental triggers (viruses, toxins, dietary factors) will be curtailed or abandoned without continued funding, and delay our ability to effectively prevent disease in at-risk populations.

Diabetes research has demonstrated a strong return on the federal investment. Continued strong federal commitment is needed.

Identifying the genetic and environmental causes of type 1 diabetes requires long term investment in large, collaborative, multi-year research projects. By the end of 2007, the Type 1 Diabetes Genetics Consortium is expected to have collected DNA samples from 2,800 families around the world that have two or more siblings with type 1 diabetes. Likewise, The Environmental Determinants of Diabetes in Youth (TEDDY) study is in the process of recruiting more than 7,000 infants who are at high risk of developing type 1 diabetes. Subject recruitment for these studies will be complete by the end of 2008. However, processing and analyzing these massive biological sample collections will require significant time, funds, and collaborative effort over the ensuing years. Substantial resources will be required until the projected end of the TEDDY study in 2021 to carefully monitor and study these children through the age of 15 years and identify environmental triggers associated with the development of type 1 diabetes.

For these reasons, funding needs for research related to identifying genetic and environmental causes of type 1 will increase moderately over the next several years so that the investment in genetic and environmental research can be fully realized.

PREVENTION OF TYPE 1 DIABETES
About 30,000 new cases of type 1 diabetes (children and adults) are diagnosed each year in the United States. One in every 400 to 600 children and adolescents now lives with this disease. Preventing type 1 diabetes before it starts would afford significant healthcare cost savings and relieve many years of human suffering. However, the prevention of type 1 diabetes will likely require an in-depth knowledge of the genes and environmental agents that cause this disease. While individuals with a type 1 diabetic relative are known to be at greater risk of developing the disease, more than 80 percent of new cases occur in individuals without such a relative. Although multiple genes for type 1 diabetes susceptibility and candidate environmental agents capable of inducing disease have been identified, their interactions and the steps towards type 1 diabetes remain unclear.

HOPE AND PROGRESS THROUGH RESEARCH
To tackle this challenge, federal funding has enabled the formation of large-scale, long-term, collaborative research projects that have afforded key information to unlock the mysteries surrounding the genetic and environmental causes of type 1 diabetes. For example:

In families that have one member with type 1 diabetes, researchers can now identify with reasonable accuracy those additional family members who are at increased risk for developing type 1 diabetes. This knowledge provides an excellent opportunity to involve high-risk individuals in clinical trials of promising disease prevention protocols, and to identify clues as to why the disease develops.

Researchers have discovered that the autoimmune processes that eventually culminate in type 1 diabetes often begin within the first 12 to 24 months of life, even though diabetes may not fully develop until years or even decades later. This important finding points to the need for prediction and prevention efforts early in life.

Approximately 50 percent of the genetic risk of type 1 diabetes comes from a single region of the genome that encodes proteins key to the immune system. Other genes recently identified — CTLA4, PTPN22, and CD25 — all code for proteins with roles in the immune response. The insulin molecule has been shown to be a primary antigen during the disease process, which confirms the finding from genetics studies that the insulin gene (INS) influences risk for diabetes. These observations emphasize the importance of understanding the immune mechanisms that contribute to type 1 diabetes.

Recent studies have shown that a gene regulated by the response to viral infections contributes to a person's susceptibility to type 1 diabetes. This result offers a possible link between type 1 diabetes and viral infections. Advances in genetics and genomics may help to identify pertinent environmental triggers of the disease, including those related to viruses or dietary practices.

In the last 5 years, extensive collections of biological samples have been assembled from people with type 1 diabetes and their families. These collections provide a platform for developing new hypotheses or testing possible new therapies for type 1 diabetes using human samples.

Go to Future Opportunities...