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Researchers May Have Uncovered Stages of Beta Cell Destruction in Type 1 Diabetes

-Trisha Gura

Researchers once believed that the onset of type 1 diabetes led to the complete destruction of insulin-producing beta cells. Recent evidence, however, suggests that most people with type 1 diabetes actually maintain residual beta cells that function long after type 1 diabetes’ onset.

To gain an understanding of the process of beta cell destruction in the hopes of generating new therapies, researchers from the T1D Exchange Clinic Network in 2015 studied 919 individuals who had type 1 diabetes for a significant amount of time. The investigators found that the majority of patients produced C-peptide, a molecule whose presence indicates that the body is producing insulin. In fact, C-peptide lasts longer in the body than insulin itself.

Next, investigators at the Indiana University School of Medicine and the T1D Exchange Residual C-peptide Study Group studied proinsulin, the precursor of insulin. Normally the body processes proinsulin into insulin and C-peptide. The goal was to track how proinsulin and its byproduct C-peptide fluctuated with the duration of the onset of type 1 diabetes.

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For the study, the researchers again studied these individuals with longstanding type 1 diabetes through analysis of samples stored in the T1D Exchange Biobank. Researchers separated participants into three groups – those who were producing high, medium, or low amounts of C-peptide. Surprisingly, researchers found that nearly all study participants were producing proinsulin, even those with low C-peptide, which should correspond to levels of its parent proinsulin. Also, only those who could convert proinsulin into insulin, as measured by C-peptide levels, were observed to increase proinsulin production in response to a meal.

From these results, the researchers speculate that there may be an observable hierarchy of beta cell dysfunction. At the onset of type 1 diabetes, beta cells can still process proinsulin into C-peptide and insulin. Over time, the cells may lose the ability, causing them to be targeted for destruction. As beta cell destruction progresses and C-peptide levels decrease, the ability to increase proinsulin after meals is reduced.

Researchers hope that by understanding the full process of beta cell destruction, they may be able to stop the process at a key moment in the onset of type 1 diabetes. More research will be needed, however, to even begin to develop therapies aimed at preserving beta-cell health.

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