A recent Scientific Short asked, “Can glycated albumin play a useful role in diabetes care?” and concluded that it may have a role in settings where hemoglobin A1c is unavailable or unreliable [1]. This analyte is more widely used outside the U.S. where an automated assay has been available for many years. A recent editorial summarizes key pros and cons as well as continued areas of controversy in this field [2]. These authors suggest that more translational studies are needed to demonstrate whether or not this assay improves care for those with diabetes.

In planning for additional translational studies, laboratorians should keep in mind preanalytical factors and analytical concerns important for consistency across studies. There are a few different methods to measure glycated albumin (GA). As with most protein analytes, standardization could be improved. One of the more traditional methods utilizes a boronate affinity column and HPLC. An enzymatic method for use on automated analyzers (Lucica, GA-L) has been available since 2002 in Japan, but was only FDA approved in the U.S. in 2017. The majority of published studies have been done using this method which is traceable to a Japanese certified reference material. Additionally, another enzymatic method for glycated serum proteins can be used with an albumin measurement and manufacturer-determined equation to produce a % GA value equivalent to the Lucica method [3]. Recently, LC-MS/MS methods have also been published.

What about interfering substances? In additional to hemoglobin, manufacturer inserts for the enzymatic methods list ascorbic acid, uric acid, and triglycerides as potential interferences. Some published papers have reported lower acceptable limits than stated by manufacturers, especially for triglycerides [4,5]. High levels of glucose are also listed as an interfering substance. This is likely more of a sample stability issue. GA is formed by the nonenzymatic reaction between glucose and albumin in the plasma, so formation does not stop when the specimen is drawn. Quick processing and appropriate storage is necessary to slow this reaction prior to measurement. Package inserts for both enzymatic methods mentioned above list only refrigerated and frozen stabilities, but nothing for room temperature. In our observations (not published), we found continued slow increase in % GA even at refrigerated temperatures. Freeze-thaws may also affect results. A recent paper showed that % GA in pristine samples (never experienced freeze-thaw) from the 1999-2004 NHANES survey was much lower than in samples previously thawed (13.8% vs 23.4%, respectively) [6]. However, in our validation, we did not find a change in % GA over three freeze-thaws. The actual variation observed is likely to depend upon the length of time the samples remain at room temperature during the freeze-thaw.

Lastly, one should be aware of factors that may play a role in interpretation of % GA. When reported as a percentage, there is no need to adjust for variations in albumin level. However, there are clinical situations where albumin turnover is altered and % GA in those situations may be more difficult to interpret. Many studies have shown a negative correlation between body mass index (BMI) and % GA. This has led to determinations of reference intervals based on BMI [7]. Other physiological conditions that may result in lower or higher % GA than expected in relation to glycemia include liver cirrhosis, hyper- or hypothyroidism, nephrotic syndrome or Cushing’s syndrome [8].


  1. Kim H, Rooney MR, Fang M, Selvin E. Can glycated albumin play a useful role in diabetes care? AACC Academy Scientific Shorts. September 13, 2022. Available from: https://www.aacc.org/science-and-research/scientific-shorts/2022/can-glycated-albumin-play-a-useful-role-in-diabetes-care
  2. Kirkman MS, Sacks DB. Glycated Albumin: Added Value or Redundancy in Diabetes Care? Clin Chem. 2022; 68:379-381.
  3. Abidin D, Liu L, Dou C, Datta A, Yuan, C. An improved enzymatic assay for glycated serum protein. Anal Methods. 2013; 5:2461-2469.
  4. Paroni R, Ceriotti F, Galanello R, Battista Leoni G, Panico A, Scurati E, Paleari R, Chemello L, Quaino V, Scaldaferri L, Lapolla A, Mosca A. Performance characteristics and clinical utility of an enzymatic method for the measurement of glycated albumin in plasma. Clin Biochem. 2007; 40:1398-1405.
  5. Rodriguez-Capote K, Tovell K, Holmes D, Dayton J, Higgins TN. Analytical evaluation of the Diazyme glycated serum protein assay on the siemens ADVIA 1800: comparison of results against HbA1c for diagnosis and management of diabetes. J Diabetes Sci Technol. 2015; 9:192-9.
  6. Daya NR, Rooney MR, Tang O, Coresh J, Christenson RH, Selvin E. Glycated Albumin in Pristine and Non-Pristine Stored Samples in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. J Appl Lab Med. 2022; 7:916-922.
  7. Selvin E, Warren B, He X, Sacks DB, Saenger AK. Establishment of Community-Based Reference Intervals for Fructosamine, Glycated Albumin, and 1,5-Anhydroglucitol. Clin Chem 2018; 64:843-850.
  8. Koga, M. Glycated albumin; clinical usefulness. Clin Chim Acta 2014; 433:96-104.