Background & Purpose

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BACKGROUND AND PURPOSE

Currently 1.6 million people in the United States have a Type 1 Diabetes (T1D) diagnosis and this number is expected to increase to 5 million by 2050. In the absence of approved disease modifying therapies to prevent or cure this disease, those with T1D are at dramatically increased risk of severe complications and an estimated 10-year reduction in life expectancy as compared to those without the disease. While some therapies have been demonstrated in clinical studies to delay the onset of or slow the progression of the disease after diagnosis, none are yet approved for use.

T1D risk is influenced by several factors including genetics, age, ethnicity, BMI, and environmental determinants. While almost 50% of the genetic contribution to T1D risk is associated with variation in the HLA alleles, many other genes have been shown to contribute to this and their relative contribution varies with age of diagnosis and ethnicity. Despite this variability, genetic predisposition to T1D has provided a valuable risk assessment tool with the most recent iterations of Genetic Risk Score (GRS) demonstrating very high specificity and sensitivity for detecting T1D risk in people of European descent.

The early stages of T1D can be detected by the presence of serum autoantibodies against the pancreatic beta cell and these are well correlated with the later development of symptomatic disease. Persistent positivity to 2 or more of the most common T1D autoantibodies (insulin – IAA, glutamic acid decarboxylase – GADA, insulinoma-associated antigen-2 – IA2A, and zinc transporter 8 – ZnT8A) indicates active autoimmunity and is classified as Stage 1 T1D. The presence of autoantibodies and signs of dysglycemia (Stage 2) is linked to a high risk of progression to symptomatic disease (Stage 3).