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Individuals at increased risk of type 2 diabetes development have increased branching and lower sialylation of alpha-1-acid glycoprotein N- glycans

Glycosylation, the addition of oligosaccharide chains is one of the most abundant co- and posttranslational modifications. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Recently, we showed that the increased branching of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes. There we measured the whole plasma protein N-glycome, which is comprised of different glycans originating from many different glycoproteins. The most likely candidate for the origin of those glycan changes is alpha-1-acid glycoprotein (AGP), since it is the source of the most branched glycan structures present in the whole plasma protein N-glycome. Using a high-throughput and site-specific AGP Nglycosylation LC-MS analysis method, we analyzed N-linked glycans on a glycopeptide level from plasma of 59 patients who developed hyperglycemia during ICU hospitalization due to an acute illness (a known predictor of type 2 diabetes) and compared them with glycans from 49 similar ICU patients who remained normoglycemic. Samples were taken after the cessation of inflammatory process was confirmed (based on blood count and CRP). Individuals at higher risk of diabetes presented increased branching and lower sialylation of alpha1acid glycoprotein N-glycans. If this is confirmed on a bigger study, it would probably help to develop stratification methods which could reliably distinguish individuals who are at risk of type 2 diabetes development.

Alpha-1-acid glycoprotein ; glycosylation ; high-throughput ; biomarker ; type 2 diabetes

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