Loss of Exocytosis Protein DOC2B is an Early Event in Type 1 Diabetes Development

Area of Science:

• Endocrinology
• Immunology
• Biomarker Discovery

Background:

• Type 1 diabetes (T1D) diagnosis often occurs after significant immune-mediated beta-cell destruction.
• Non-invasive biomarkers for early presymptomatic detection of beta-cell dysfunction are lacking.
• Previous work identified reduced platelet DOC2B as a marker for reduced beta-cell function.

Purpose of the Study:

• To evaluate plasma double C2-like domain containing beta protein (DOC2B) as an early biomarker for T1D progression risk.
• To assess DOC2B's utility in distinguishing between T1D progressors and non-progressors in a pediatric cohort.
• To explore DOC2B as a reporter of beta-cell functional mass post-transplantation.

Main Methods:

• Analysis of plasma DOC2B levels in an autoantibody-positive pediatric cohort (DEW-IT study) comparing progressors and non-progressors.
• Comparison with T1D patients and non-diabetic controls from the DEW-IT study.
• Assessment in prediabetic nonobese diabetic (NOD) mice and T1D patients before and after islet transplantation.

Main Results:

• Plasma DOC2B levels declined in T1D progressors before changes in C-peptide or HbA1c.
• Non-progressors maintained stable DOC2B levels.
• DOC2B levels reflected changes in beta-cell functional mass after islet transplantation in T1D patients.

Conclusions:

• Plasma DOC2B decline may precede C-peptide decline in early presymptomatic T1D.
• DOC2B shows potential as a sensitive, non-invasive biomarker for T1D progression.
• This biomarker could inform clinical trial stratification and assess therapeutic responses in T1D.