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Heterogeneity

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 https://diabetesresearchconnection.org.

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Role of the integrated stress response in type 1 diabetes pathogenesis
In individuals with type 1 diabetes (T1D), the insulin-producing beta cells are spontaneously destroyed by their own immune system. The trigger that provokes the immune system to destroy the beta cells is unknown. However, accumulating evidence suggest that signals are perhaps first sent out by the stressed beta cells that eventually attracts the immune cells. Stressed cells adapt different stress mitigation systems as an adaptive response. However, when these adaptive responses go awry, it results in cell death. One of the stress response mechanisms, namely the integrated stress response (ISR) is activated under a variety of stressful stimuli to promote cell survival. However, when ISR is chronically activated, it can be damaging to the cells and can lead to cell death. The role of the ISR in the context of T1D is unknown. Therefore, in this DRC funded study, we propose to study the ISR in the beta cells to determine its role in propagating T1D.
Wearable Skin Fluorescence Imaging Patch for the Detection of Blood Glucose Level on an Engineered Skin Platform
zhang
A Potential Second Cure for T1D by Re-Educating the Patient’s Immune System
L Ferreira
Validating the Hypothesis to Cure T1D by Eliminating the Rejection of Cells From Another Person by Farming Beta Cells From a Patient’s Own Stem Cells
Han Zhu
Taming a Particularly Lethal Category of Cells May Reduce/Eliminate the Onset of T1D
JRDwyer 2022 Lab 1
Can the Inhibition of One Specific Body Gene Prevent Type 1 Diabetes?
Melanie
Is Cholesterol Exacerbating T1D by Reducing the Functionality and Regeneration Ability of Residual Beta Cells?
Regeneration Ability of Residual Beta Cells
A Call to Question… Is T1D Caused by Dysfunctionality of Two Pancreatic Cells (β and α)?
Xin Tong
Novel therapy initiative with potential path to preventing T1D by targeting TWO components of T1D development (autoimmune response and beta-cell survival)
flavia pecanha