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Measurement of Differentially Methylated INS DNA Species in Human Serum Samples as a Biomarker of Islet β Cell Death
Published on: December 21, 2016
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β cell death and dysfunction during type 1 diabetes development in at-risk individuals
The Journal of Clinical Investigation
|February 3, 2015
Summary
A new blood test can detect early signs of type 1 diabetes (T1D) by measuring unmethylated insulin DNA, indicating active beta cell killing years before diagnosis.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- Type 1 diabetes (T1D) involves beta cell destruction, which begins years before clinical symptoms.
- The primary pathological process of T1D, beta cell killing, has not been directly measured previously.
Purpose of the Study:
- To measure beta cell death in individuals at risk for T1D.
- To identify a blood-based biomarker for early detection of T1D-associated beta cell destruction.
Main Methods:
- An observational study involving 50 at-risk participants from the TrialNet Pathway to Prevention study and 4 islet autotransplant recipients.
- Measurement of beta cell death using an assay detecting unmethylated insulin (INS) DNA in blood.
Main Results:
- Individuals progressing to T1D showed elevated unmethylated INS DNA levels compared to healthy controls.
- Increased unmethylated INS DNA correlated with decreased insulin secretion, confirming it as a marker of beta cell killing.
- High-risk individuals who developed T1D had higher unmethylated INS DNA levels than healthy controls and those who did not progress.
Conclusions:
- A blood test measuring unmethylated INS DNA is a reliable marker for active beta cell killing in T1D-associated autoimmunity.
- Beta cell destruction in T1D occurs sporadically years before diagnosis and intensifies around the time of diagnosis.
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