Glycated Albumin (GA)

Diagnostic Use

Glycated albumin (GA) is a marker for diabetes control, which has gained prominence in the literature over the past few years. Though the mainstay of diabetes monitoring and screening is glycated haemoglobin (HbA1c), there are patients who have haemoglobin variants, or abnormalities in red blood cell turnover such as haemolytic anaemia, thalassaemia, renal failure, or recent blood transfusion where HbA1c is unreliable. Furthermore, when it is desirable to get faster feedback on diabetes control, such as stepping up treatment in poorly controlled diabetes or in pregnancy, a marker for glycaemic control with a shorter time window than HbA1c is useful.

GA has a half life of monitoring of two to three weeks, and provides information on approximately half the time of HbA1c prior to collection. The most similar analyte being measured currently is fructosamine, which is a measurement of total glycated serum proteins, of which approximately 90% is thought to reflect GA. However, fructosamine has been shown to have unexpected changes in some patients with stable glycaemic control based on other markers such as mean blood glucose, HbA1c and GA. Although glycated albumin had very high correlation with fructosamine, the correlation of glycated albumin with HbA1c or with mean blood glucose was better than the correlation of fructosamine with the same analytes. Furthermore, GA inherently corrects for variation in albumin concentration, whereas correction of fructosamine for total protein is not routine, and has not shown unequivocal benefit, conceivably due to heterogeneity between different proteins.

Data available from Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC), Atherosclerosis Risk in Communities (ARIC) and National Health and Nutrition Examination Survey (NHANES) studies has shown an association of high GA with all-cause mortality, cardiovascular mortality, coronary heart disease, incident chronic kidney disease, microalbuminuria, and retinopathy.

References:
1. Ciaccio M. Introduction of glycated albumin in clinical practice. J Lab Precis Med. 2019;4:28.
2. Desouza CV, Holcomb RG, Rosenstock J, et al. Results of a Study Comparing Glycated Albumin to Other Glycemic Indices. J Clin Endocrinol Metab. 2020;105(3):677-687.
3. Takei I, Hoshino T, Tominaga M, et al. Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry-recommended reference measurement procedure and reference materials for glycated albumin determination. Ann Clin Biochem. 2016;53(Pt 1):124-132.
4. Nathan DM, McGee P, Steffes MW, Lachin JM; DCCT/EDIC Research Group. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes. 2014;63(1):282-290.
5. Selvin E, Rawlings AM, Grams M, et al. Fructosamine and glycated albumin for risk stratification and prediction of incident diabetes and microvascular complications: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Lancet Diabetes Endocrinol. 2014;2(4):279-288.
6. Selvin E, Rawlings AM, Lutsey PL, et al. Fructosamine and Glycated Albumin and the Risk of Cardiovascular Outcomes and Death. Circulation. 2015;132(4):269-277.
7. Rooney MR, Daya N, Tang O, et al. Glycated Albumin and Risk of Mortality in the US Adult Population. Clin Chem. 2022;68(3):422-430.

Department

Specialist Biochemistry

Delphic Registration Code

GA

Laboratory Handling

Separating

Separate and freeze aliquot within six hours of collection

Test Adds

Refer to additional specimen information for stability data

Synonyms

Glycosylated albumin,
glycated serum albumin,
glycated HSA,
GSA

Turnaround Time

1 week

Test Code

GA

Specimen Type

• Serum
• Plasma
• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• Serum (Red Cap)

Acceptable

• SST II (Gold Cap)
• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

0.5

Minimum Sample Volume (ml)

0.05

No of Samples Required

1

Interferences

Slight overrecovery with very high haemolysis and glucose (25 mmol/L)
Possible interference from some albumin variants (uncommon), very high des-Leu albumin (chronic pancreatitis) and penicillins
small negative bias of EDTA plasma vs serum for our method

Additional Specimen Information

Stability:
Room temperature: 6 hours
2-8 °C: 7 days
-20 °C: 2 weeks
-70/-80 °C: 19-23 years
Freeze-thaw cycles: 20 cycles

Samples with high glucose are less stable due to in vitro glycation. The above values represent conservative stability data in presence of high glucose

Aliquot Instructions

Sample Type

• Serum
• Plasma

Minimum Volume (ml)

0.5

Transport to Lab

Chilled (2 - 8 degrees Celsius)
Frozen

Additional Referral/Aliquot Information

Avoid prolonged time at room temperature due to in vitro glycation.
Serum or plasma should be separated from RBC ASAP, and kept refrigerated or frozen before analysis.

Interpretation

A lower GA is seen in patients with higher BMI for the same HbA1c, which may explain discrepancy between general population data (mostly T2DM, eg ARIC or NHANES) and T1DM (DCCT/EDIC).

Very low GA can be seen in nephrotic syndrome, due to shorter time of albumin in circulatory system for glycation to occur, and GA is not a reliable diabetes marker in this context.

GA should not be interpreted after recent albumin infusion within the past month.

GA decreases throughout the course of normal pregnancy, becoming lowest in the third trimester. However, reference intervals vary depending on the population. The local GA reference intervals in pregnancy and decision limits need further study.

To convert from GA (mmol/mol) to GA (% Lucica/Asahi-Kasei) seen commonly in the literature, the following formula may be used:

(GA % Lucica) = -0.4217 + 0.05652 * (GA mmol/mol)

References:
1. Nathan DM, McGee P, Steffes MW, Lachin JM; DCCT/EDIC Research Group. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes. 2014;63(1):282-290.
2. Selvin E, Rawlings AM, Grams M, et al. Fructosamine and glycated albumin for risk stratification and prediction of incident diabetes and microvascular complications: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Lancet Diabetes Endocrinol. 2014;2(4):279-288.
3. Selvin E, Rawlings AM, Lutsey PL, et al. Fructosamine and Glycated Albumin and the Risk of Cardiovascular Outcomes and Death. Circulation. 2015;132(4):269-277.
4. Sato A, Yada S, Hosoba E, Kanno H, Miura H. Establishment of glycated albumin unit conversion equation from the standardized value (mmol/mol) to the routinely used value (%). Ann Clin Biochem. 2019 Mar;56(2):204-209.

Reference Intervals

160-290 mmol/mol (non-pregnant adult)

Test Method

Electrospray ionisation (ESI) Time-of-Flight (TOF) Mass spectrometry

Contact Canterbury Health Laboratories on +64 3 364 0484 or email LabInfo@cdhb.health.nz

This test may be vetted by a pathologist or scientist. To prevent delay or test being declined, please indicate the reason for the test. Appropriate indications may include suspected interference or unreliability of HbA1c (eg haemoglobin variant, recent blood transfusion, haemolysis, iron deficiency, renal failure), recent intensification of diabetes treatment, or pregnancy.

Requests from an endocrinologist, diabetes physician or chemical pathologist will be automatically approved.

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