Protein glycation: measurement and clinical relevance.

This review of protein glycation deals with the biochemical background of glycated blood proteins, their methods of determination and their clinical significance. General reaction principles for determination of glycated proteins are discussed with special emphasis on the determination of glycated serum proteins in the clinical laboratory. Binding methods like boronate affinity, immunoassay, phenylhydrazine binding and ion exchange chromatography leave the analyte intact, whereas chemical methods like strong or mild hydrolysis or reduction in alkaline medium (fructosamine assay) results in destruction of the glycated protein. As most reactions are nonstoichiometric (except ion exchange chromatography and periodate oxidation), varying results are obtained from laboratory to laboratory. Up to now boronate affinity chromatography, mild hydrolysis yielding hydroxymethylfurfural and the fructosamine assay have been mostly used for determination of glycated serum proteins. The fructosamine assay appears to be most practical, because it is quick, economic and precise, but it suffers from unspecific side reactions. Although other methods like immunoassays or boronate ester formation in solution appear promising, there is currently no commercially available assay for the economic, precise and accurate determination of glycated serum protein. The clinical relevance of glycated serum protein determination is difficult to evaluate because the assays are based on different reaction principles and hence yield variable results. Nevertheless, the following conclusion may be drawn from the reports now available. i) The possibility that glycated serum proteins may discriminate better than glycated haemoglobin between "normal" and "diabetic" is still controversial. ii) Glycated serum proteins are formed faster than glycated haemoglobin, reflecting the changes in glycaemia for shorter periods of time (medium-term control). iii) It has not been yet established, using large cohorts, whether the glycated serum proteins allow the detection or exclusion of diabetes. iv) Determination of glycated serum proteins should not be considered as a substitute for the determination of glycated haemoglobin, but rather as a complementary determination, leading to the improved laboratory control of the diabetic patient.