Non-hypothesis-driven identification of protein glycation in diabetes
We used our patented DDA proteomics methodology to investigate protein and post-translational markers of type II diabetes in a small (30-person) carefully controlled study comparing patients with healthy controls. We found no significant differences between patients and controls in the levels of any total protein measure.
Our patented method, however, has exceptional precision and accuracy in the measurement of not just proteins but individual peptides. This gives us the capability to investigate changes in individual PTMs without requiring any pre-selection of the PTM to be analysed either in the sample prep stage or during data analysis. Carrying out this unbiased analysis we identified 8 PTMs that had positive correlations with fasting glucose measurements from the same subjects, and survived false discovery rate correction.
Every single one of these PTMs were glycation events on major serum proteins. No other PTM was found to be associated with fasting glucose, and of the total of 13 glycation sites we identified across the serum proteome 10 had positive correlations with unadjusted p < 0.05.
While glycation of major serum proteins in subjects with a higher fasting glucose is not biologically surprising, this data showed the ability of our ProQuant® platform technology to identify in a non-hypothesis driven manner key protein modifications in a hugely complex system.
Notably, these interesting glycation events are found on four of the major serum proteins, all of which have slightly shorter half-lives than haemoglobin, ranging from around 5 to 15 days. It is likely, therefore, that analysis of several of these sites in conjunction with glycated haemoglobin (HbA1c; used clinically as a biomarker for elevated blood glucose) would provide clinicians with an indication of the direction of movement of fasting glucose over the preceding 2 to 8 weeks.
This data is described more fully in our preprint: https://www.biorxiv.org/content/10.1101/2024.03.19.585746v1
