Advancements in Characterizing Type 1 Diabetes Heterogeneity

No two people with type 1 diabetes are exactly the same. Each experiences disease progression differently, and the genetic and biological factors that impact this process differ as well. This can make understanding how type 1 diabetes initially develops and the risk factors involved more challenging.

A recent study examined islet autoimmunity and heterogeneity across a group of 80 individuals diagnosed with juvenile-onset type 1 diabetes. Some had only been recently diagnosed while others had been living with the disease for many years. The study evaluated immunological, genetic, and clinical differences between individuals in order to create more detailed profiles and stratify findings.

Blood samples were taken and testing conducted to determine T-cell response to various beta cell antigens including GAD65, islet antigen-2 (IA-2), preproinsulin (PPI), and defective ribosomal product of the insulin gene (INS-DRIP). Results show that some individuals were high responders showing T-cell proliferation for all four beta cell antigens, some were intermediate responders showing proliferation to one to three beta cell antigens, and the rest were non-responders who did not show any T-cell proliferation response to the tested beta cell antigens.

In addition, more than 80 percent of participants were categorized as high risk by having an HLA-DR-DQ genotype that is associated with development of type 1 diabetes. High responders also had higher non-HLA genetic risk scores than the other two groups. Another interesting finding was that individuals who had longer disease durations also showed an increase in beta cell-specific T-cell proliferation.

Though a larger study is needed to further build out full immunological heterogeneity and explore the interactions between different variables, this study is a strong starting point. Better understanding the complete profile of individuals with type 1 diabetes and how their body responds to different factors could lead to more individualized treatment to help manage the disease. Researchers can tailor treatment toward which beta cell antigens a person responds to, whether they or not they have high HLA-DR-DQ risk or not, as well as other variables.

The body of knowledge surrounding type 1 diabetes is always growing and improving. This is critical to advance prevention and treatment options. Diabetes Research Connection (DRC) supports early career scientists in pursuing novel research studies in order to continue moving understanding forward. Learn more about current projects and how to help by visiting

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