Proximity extension assay inflammatory profiling cannot distinguish the presence of residual C-peptide in patients with long-standing type 1 diabetes.

Objective: Many patients with long-standing type 1 diabetes (T1D) have remaining low levels of C-peptide, i.e. and indirect sign of remaining functional beta-cells. This study focused on identifying differences in immunological and inflammatory biomarkers in patients with longstanding T1D and remaining C-peptide.

Research design and methods: Adult patients (n = 120) with long-standing T1D (≥ 10 years) and healthy controls (HC) (n = 50) were recruited at Uppsala University Hospital. Residual beta-cell function was determined with an ultrasensitive C-peptide ELISA under fasting conditions. T1D patients were divided into two groups (C-peptide positive vs. C-peptide negative). Using the OLINK Explore Inflammation proximity extension assay (PEA), 368 circulating immunological and inflammatory biomarkers were analyzed in plasma.

Results: The three groups could not be distinguished by principal component analysis and when correcting for multiple testing we found no differences in circulating biomarkers. However, based on uncorrected p-values there were six biomarkers that were different when comparing all T1D patients with HC and eight markers that were different when comparing C-peptide positive vs. negative T1D patients.

Conclusion: A wide inflammatory assay analysis cannot distinguish patients with longstanding T1D and remaining C-peptide from patients with a complete loss of C-peptide nor from HC.