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.