About GA

About glycated albumin (GA)

Glycated albumin (GA) is an intermediate glycemic control maker (preceding two to three weeks) used in the glycemic control of patients with diabetes. Asahi Kasei Pharma Corporation developed Lucica® GA-L, which is liquid reagents that measures glycated albumin using a unique enzymatic method approved by the US FDA.

Point 1: Albumin is a protein that can be easily glycated.

Glycated albumin (GA)

Glycated albumin (GA) is a product from the glycation of serum albumin and is defined as albumin containing lysine residues bound to glucose (glycated lysine).

Fig. 1 The structure of human serm albumin

Albumin glycation sites

Albumin is the most abundant protein in human blood.
Human serum albumin contains 59 lysine residues. Four lysine residues ( red in Fig.1) are mainly glycated in albumin.1

1)Iberg N and Flückiger R, J Biol Chem. 1986;261(29):13542-5.

Point 2: GA is an intermediate term (preceding two to three weeks) glycemic control marker used to confirm the therapeutic effect.

Relationship between GA and past blood glucose level

GA reflects the glycemic status in the preceding two to three weeks because the half-life of glycated albumin (GA) is about 17 days2.

The relationship between GA and past blood glucose level

Fig. 2 Relationship between glycated proteins and past plasma glucose levels (based on Reference 2)

2)Tahara Y and Shima K, Diabetes Care. 1995;18(4):440-7.

Confirming the therapeutic effects when treatment starts or changes

In 30 patients receiving glucose-lowering therapy (prospective multicenter study in the United States), changes in GA at four weeks were concordant with changes in A1C at twelve weeks.3

3) Desouza CV, et al., Endocr Pract. 2015 Nov;21(11):1195-203.

Comparing Glycated Albumin to Other Glycemic Indices (24-week prospective study of assay performance in the United States)

In the 24-week prospective study, changes in GA between study visits were concordant (increased or decreased in the same direction) with MBG changes 60.8% of the time, with fructosamine changes 55.5% of the time, and with A1C 45.5% of the time.4


Design: 24-week prospective study of assay performance. Eight US clinics.
Subjects: Type 1 (n = 73) and type 2 diabetes (n = 77) undergoing changes to improve glycemic control (n = 98) or with stable diabetes therapy (n = 52).
Interventions: GA, fructosamine, and A1C measured at prespecified intervals. Mean blood glucose (MBG) calculated using weekly self-monitored blood glucose profiles.

4) Desouza CV, et al., J Clin Endocrinol Metab. 2020 Mar 1;105(3).
Desouza CV, et al., Results of a Study Comparing Glycated Albumin to Other Glycemic Indices. https://doi.org/10.1210/clinem/dgz087
©2019 Desouza CV, et al. ; licensee Oxford University Press
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)

Difference between GA and Fructosamine

Fructosamine is a generic term that refers to all glycated serum proteins, including glycated albumin, in blood serum. Lucica® GA-L selectively measures glycated albumin. The fructosamine assay measures the total concentration of glycated serum proteins, which can fluctuate because of acute systemic illness or liver disease. However, glycated albumin assays, such as Lucica® GA-L, measure the ratio of glycated albumin to total albumin, which minimizes interference from concentrations of glycated and non-glycated albumin.

Point 3: GA is used in glycemic control when other glycemic control markers are inconsistent with the blood glucose level (e.g., patients undergoing hemodialysis or pregnant women with diabetes or gestational diabetes mellitus).

Because the GA is produced through the glycation of human serum albumin, it is not affected by pathologies with the erythrocyte lifespan altered, such as renal anemia, under treatment with dialysis or erythropoietin, iron-deficiency anemia, or the recovery phase of iron deficiency anemia.

On the other hand, attention is necessary in pathologies with the albumin metabolism altered.

Pathologies presenting higher GA levels with respect to blood glucose levels
Diseases with albumin metabolism delayed: Hypothyroidism,5 hepatic cirrhosis,6 and emaciation7
Pathologies presenting lower GA levels with respect to blood glucose levels
Diseases with albumin metabolism enhanced: Hyperthyroidism,5 treatment with glucocorticoids,8 Cushing’s syndrome,9 nephrosis,10 and advanced obesity11

5) Koga M, et al., Diabetes Res Clin Pract. 2009 May;84(2):163-7.
6) Miyamoto H, et al., Rinsho Byori. 2008 Sep;56(9):761-6. Japanese.
7) Koga M, et al., Clin Chim Acta. 2007 Mar;378(1-2):48-52.
8) Iizuka K, et al., BMJ Case Rep. 2016 Mar 9;2016 pii: bcr2016214788
9) Kitamura T, et al., Clin Chim Acta. 2013 Sep 23;424:164-7.
10) Okada T, et al., Intern Med. 2011;50(1):23-9.
11) Koga M, et al., Clin Chim Acta. 2015 Jan 1;438:19-23.

Glycemic control indices for patients undergoing hemodialysis

Relationship between casual blood glucose and GA in diabetic patients (cases with hemodialysis/normal renal function) (Japan)

HbA1c levels in hemodialysis patients with diabetes (B) were significantly lower than those in diabetic patients without CRF (D).
The GA levels in hemodialysis patients with diabetes (A) were almost the same as those in diabetic patients without CRF (C).
GA is shown to be useful as an index for glycemic control in hemodialysis patients with diabetes.
Hemodialysis (HD) patients with diabetes
Diabetic patients without chronic renal falure (CRF)

 

 

GA

 

 

HbA1c

 

 

GA

 

 

HbA1c

 

 

The regression slope between HbA1c and plasma glucose (PG) was significantly more shallow in HD patients with diabetes (0.012) compared with diabetic patients without CRF (0.021; p < 0.001), although the slope between GA and PG did not differ significantly between the two groups of patients (0.068 versus 0.058; p > 0.10).

Used with permission of American Society of Nephrology, from Glycated Albumin Is a Better Glycemic Indicator Than Glycated Hemoglobin Values in Hemodialysis Patients With Diabetes: Effect of Anemia and Erythropoietin Injection, M inaba et al., 18(3), 2007; permission conveyed through Copyright Clearance Center, Inc.

 

Vital prognosis and GA in hemodialysis patients with diabetes

In a four-year follow-up study, the Kaplan-Meier method indicated a lower mortality risk in the GA <20% group than other groups ( GA 20.0-24.5% and GA >24.5% groups) in 108 hemodialysis patients with diabetes without a history of CVD. No significant difference was noted in the survival rate in 70 cases with a history of CVD.

Inaba M, et al. Impact of atherosclerosis on the relationship of glycemic control and mortality in diabetic patients on hemodialysis Clin Nephrol 2012. 78 (4), 273-80.

 

Targets for glycemic control in diabetic patients on hemodialysis (Japan)

“Best Practice for Diabetic Patients on Hemodialysis 2012” issued by the Japanese Society for Dialysis Therapy includes the following description in the Targets for Glycemic Control Statements.

Pre-dialysis casual plasma glucose and glycated albumin (GA) levels are recommended as indicators for glycemic control.
The hemoglobin A1c (HbA1c) level might be used only as a reference, because the HbA1c level decreases in the presence of anemia or erythropoiesis-stimulating agents (ESAs) and may not accurately represent glycemic control in hemodialysis patients.

 

Tentative targets for glycemic control

Pre-dialysis casual plasma glucose levels (or 2-h postprandial plasma glucose levels) <180–200 mg/dL
For hemodialysis patients, GA levels <20.0% are recommended
For hemodialysis patients with a history of cardiovascular events and who have hypoglycemic episodes, GA levels <24.0% are suggested.
*Further studies are required to definitively determine target values.

Nakao T. et al., Best practice for diabetic patients on hemodialysis 2012.Ther Apher Dial. 2015 Mar;19 Suppl 1:40-66.

GA in pregnant women with diabetes or gestational diabetes mellitus

GA is less susceptible to the effect of maternal iron metabolism and therefore useful in strict glycemic control during pregnancy.

Referential information:

Standard range in normal pregnancy (Japanese pregnant women)
GA: 11.5 to 15.7%

Hiramatsu Y et al., Endocr J. 2012(59):145-151

Relationship between GA levels during pregnancy and birth weight/neonatal complications

The following reports are available:
1) Sugawara D. et al., “Glycated albumin level during late pregnancy as a predictive factor for neonatal outcomes of women with diabetes.” J Matern Fetal Neonatal Med 2018 (15):2007-2012
2) Li HP. et al., “Association between glycemic control and birthweight with glycated albumin in Chinese women with gestational diabetes mellitus.” J Diabetes Investig 2016 Jan;7(1):48-55.

 

Privacy PolicyTerms and ConditionsContact Us