HbA1C : its limitations and alternatives
Osman CAGLAR
HbA1C is the mainly used biomarker in the glycemic monitoring in diabetic patients. The dosage may be altered in some clinical situations such as hemoglobinopathies, hemolysis, chronic renal failure (CRF), splenomegaly, hereditary spherocytosis or even pregnancy, leading clinicians to question its reliability. Glycated albumin (GA), Fructosamine (FA) and continuous glucose monitoring (CGM) devices are presented as alternatives by guidelines, but their clinical use remains unclear.To asses the usefulness of the alternatives in diagnosis and follow-up of diabetesA narrative review with a methodology borrowed from a scoping review was carried out. A bibliographic research inspired by the PRISMA recommendations was conducted on the Pubmed and Cochrane databases to identify systematic reviews, narrative reviews and meta-analyses comparing these alternatives to HbA1C, published between 2015 and 2025. Results from selected studies have been compared to guidelines from 3 professional organizations : American Diabetes Association (ADA), National Institute for Health and Care Excellence (NICE) and European Association for the Study of Diabetes (EASD).Although GA has its own limitations, a better correlation with blood glucose variations in CRF than HbA1C has been shown in some studies. The diagnostic accuracy of FA seems to be lower than GA. CGM devices are more accurate at detecting blood glucose variations and help to reduce episodes of hypoglycemia.Low level of evidence and practical limitations currently prevent the use of these alternatives in clinical practice. GA seems most promising in hemodialysis patients and CGM devices in patients with significant glycemic variability. FA is the least studied marker.When HbA1C lacks reliability, alternatives appear to show some usefulness. FA remains the least studied marker, AG and CGM devices appear to show stronger evidence. Although these alternatives have been integrated into recent guidelines, a lack of harmonization between the professional organizations is currently observed. Further studies are needed to validate their clinical utility.
