What is the pattern of glycation seen in diabetes and how does it correlate with a spot glucose measure?

Glycated haemoglobin (HbA1c) is used clinically as a biomarker for elevated blood glucose, because the rate of formation of glycated haemoglobin is proportional to the free blood glucose concentration.  HbA1c has a half-life of 7-8 weeks, so HbA1c provides information on the average concentration of blood glucose for 1-3 months.

But how many other proteins are glycated?  Does every protein, and indeed every solvent-exposed free amine get glycated to the same extent?  HbA1c is used primarily because it was the first to be discovered, but are there other glycation events in the circulating proteome that correlate better with glucose concentration over time?

We used ProQuant™ to explore these questions.  Serum samples from patients with type 2 diabetes and a range of fasting glucose concentrations were compared with samples from normoglycemic subjects.  And what we found was fascinating: we detected 13 glycation sites across the human serum proteome (after depletion of the most abundant proteins), but 10 of these had positive correlations with fasting glucose with unadjusted p values < 0.05, and 8 of those survived false discovery rate correction.

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 HbA1c would provide clinicians with an indication of the direction of movement of fasting glucose over the preceding 2 to 8 weeks.