Just like the established diabetes marker, hemoglobin A1c (HbA1c), gives a snapshot of the disease in preceding 90 days, both GA and fructosamine gives similar assessment for 30 days. In fact, Martina et al. demonstrated that plasma fructosamine was a reliable alternative of glycohemoglobin in subjects with hemoglobinopathy.3
What is the difference between fructosamine and GA? The two assays are analytically comparable. In terms of clinical utility, the difference is minimal. Fructosamine assays measure glycated proteins in serum or plasma and can have traceability to the same Japanese certified reference material as glycated albumin2. Albumin is the predominant protein present in serum/plasma. Thus, GA is the main component of fructosamine whose assay results are expressed in molar concentration, µmol/L or can be expressed normalized as percent albumin. Where does the name, fructosamine, come from? Since the analyte is formed non-enzymatically when glucose binds to the amino groups of serum proteins to create the labile Schiff's base; the latter undergoes an Amadori rearrangement to form the stable analyte, fructosamine. HbA1c and fructosamine are highly correlated. The relationship between the fructosamine level and the HbA1c level can be present as a linear regression analysis, as follows4:HbA1c = 0.017 X fructosamine level (µmol/L) + 1.61.
There are two main methods that are used to measure serum or plasma fructosamine: dye-binding and enzymatic. In the former, fructosamine reduces nitroblue tetrazolium (NBT) dye, forming a colored end-product (purple) under alkaline conditions. This method suffers from various sources of interference (for example, bilirubin, hemoglobin, ascorbic acid, etc.)5. In the enzymatic method proteinase K is used to digest the glycated protein to yield glycated protein fragments. In one commercial version of the method, the enzyme, fructosaminase is then used to oxidize the ketoamine bond of the glycated protein fragments to yield H2O2, which can be measured colorimetrically on an autoanalyzer via the Trinder reaction. Glycated proteins are used as calibrators. Published reference intervals are: fructosamine 202-282 µmol/L6 as compared to GA 11.9-15.8%7.
In summary, fructosamine or glycated albumin are medium-term markers for diabetes, useful when HbA1c cannot be used such as in patients with hemoglobin variants.
- Kim H, Rooney MR, Fang M, Selvin E. Can glycated albumin play a useful role in diabetes care? AACC Scientific Short, Sept 2022
- Powers-Carson J. Glycated Albumin - What do laboratorians need to know to be ready for this testing? AACC Scientific Short, Jan 2023.
- Martina WV, et al. β-N-Terminal Glycohemoglobins in Subjects with Common Hemoglobinopathies: Relation with Fructosamine and Mean Erythrocyte Age. Clin Chem 1993;39: 2259-2265.
- Masharani U, German MS. Pancreatic hormones and diabetes mellitus. Gardner DG, Shoback D, eds. Greenspan's Basic and Clinical Endocrinology. 10th ed. New York, NY: McGraw-Hill Education; 2018. 628.
- Kruse-Jarres JD et al. A new colorimetric method for the determination of fructosamine. Lab Med 13:245-253 (1989).
- Abidin D, Liu L, Dou C, Datta A and Yuan C. An improved enzymatic assay for glycated serum protein. Anal. Methods, 2013; 5:2461.
- Kohzuma T, et al. Basic Performance of an Enzymatic Method for Glycated Albumin and Reference Range Determination. J Diabetes Sci Technol. 2011 Nov; 5(6): 1455–1462.