Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions

• DOI: 10.2337/dc15-2727
• Publication Date: 2016-07-25T13:23:01Z
• Authors: Kerry J. Welsh; M. Sue Kirkman; David B. Sacks
• Keywords: Amadori rearrangement; Glycated hemoglobin; Fructosamine

Blood oligosaccharides are attached to many proteins after translation, forming glycoproteins. Glycosylation refers an enzyme-mediated modification that alters protein function, for example, their life span or interactions with other (1). By contrast, glycation a monosaccharide (usually glucose) attaching nonenzymatically the amino group of protein. Glycated hemoglobin is formed by condensation glucose select acid residues, commonly lysine, in form unstable Schiff base (aldimine, pre-HbA1c) (Fig. 1). The may dissociate undergo Amadori rearrangement stable ketoamine.

Figure 1 Formation glycated A reversible interaction between primary (depicted as NH2) and carbonyl d-glucose yields labile intermediate, called base. This can slow spontaneous ketoamine. HbA1c if attaches N-terminal valine β-chain hemoglobin. If plasma, fructosamine albumin results. RBC, red blood cell.

Glycated hemoglobin, particularly HbA1c, has decades been widely incorporated into management (and, more recently, diagnosis) patients diabetes. An important attribute occurs continuously over lifetime protein, so concentration reflects average value period time. contrasts measurement glucose, which reveals at instant sampled acutely altered multiple factors such hormones, illness, food ingestion, exercise (2). While far most extensively used—and studied—glycated (2–4), have evaluated clinical studies include fructosamine, albumin, …