Beyond HbA1c: Current and Emerging Glycation Biomarkers for Diabetes Diagnosis, Monitoring and Risk Stratification

In patients with diabetes, the concentration of glycated proteins increases. Among them is glycated hemoglobin (HbA1c), which is currently the standard biomarker for assessing long-term glycemic control. However, this parameter has certain limitations, as several medical conditions can affect total hemoglobin levels and, consequently, HbA1c concentrations. Therefore, alternative biomarkers for glycemic monitoring are sought. Other plasma proteins, including albumins and immunoglobulins, are also glycated. In practice, fructosamine and glycated albumin (GA) and glycated CD59 (GC59) are used. Still not established in diagnostics, but scientifically widely evaluated, are also parameters such as AGEs receptors, especially sRAGE, and various types of small-molecule AGEs, such as Nε-carboxymethyl-lysine (CML) and Nε-carboxyethyl-lysine (CEL). The possibility of non-invasive measurement of AGEs fluorescence in the skin is also discussed. In addition to reviewing glycation parameters, this review emphasizes the importance of distinguishing glycation from glycosylation and highlights the need for timely and accurate diagnosis to help curb the growing burden of diabetes in developed countries. It also discusses future perspectives on the use of glycation parameters in diabetes diagnosis.