International comparison of C-peptide measurements.

BACKGROUND

C-peptide measurement has been widely used as a marker of insulin secretion in patients with diabetes. We assessed the comparability of C-peptide results obtained with different methods and by different laboratories and determined whether C-peptide results could be harmonized by normalization with a WHO reference reagent or with plasma.

METHODS

We sent 16 different heparin plasma samples to 15 laboratories in 7 countries. The samples were analyzed with 10 different assay methods. A WHO C-peptide standard was also sent to each laboratory and used to determine the feasibility of normalizing results. To assess the impact of calibrator matrix on the comparability of results, we also used the mean results of all laboratories for 4 of the samples to normalize the remaining sample results.

RESULTS

Between-laboratory variability increased with increasing C-peptide concentrations. Normalization of results with WHO reference reagents did not improve comparability, but normalization with samples significantly improved comparability among laboratories and methods. The 95% confidence interval estimate for the SD for the lab/method effect (0.0-0.061) using sample-normalized values did not overlap with the 95% CI estimate with the raw data (0.090-0.225).

CONCLUSIONS

C-peptide results generated by different methods and different laboratories do not always agree, especially at higher concentrations of C-peptide. These data support the concept of using a single laboratory for multisite studies and support efforts to harmonize C-peptide measurements by use of calibrators prepared in the sample matrix.