Outline of the Glycated Albumin (GA)

Diabetes afflicts an increasing number of people worldwide each year. Proper blood glucose

control is essential in preventing complications associated with diabetes, such as

neuropathy, nephropathy and retinopathy.

Glycated albumin (GA) is one marker used to ascertain glycemic control. GA reflects mean

glycemia over the three weeks prior to blood sampling.

Asahi Kasei Lucica® GA-L liquid reagents measure GA using conventional automated

analyzers, permitting rapid and accurate results across a range of clinical settings.

What's Glycated Albumin (GA)? 1st page

What's Glycated Albumin (GA)?

Glycation is the bonding of a sugar molecule, such as glucose, to a lipid or protein molecule,

such as albumin. Thus, glycated albumin refers to albumin to which glucose has bonded.

Albumin is present not only in blood, but also in major organs and body fluids. Albumin

serves to maintain cell shape and plays an important function in the distribution of hormones,

nutrients and some drugs in the body.

The amount of glycated albumin decreases when blood glucose levels are low and

increases when blood glucose levels are high.

When is Glycated Albmin measured?

Glycated albumin is measured when diabetes therapy is initiated to determine medication

regimens and doses and to assess overall therapy efficacy.

The following disorders can markedly alter albumin and hemoglobin life spans, potentially

affecting measurement values.

Glycated albumin ··········nephrosis, cirrhosis, and thyroid functional disorder

Glycated hemoglobin ···anemia, renal failure, and cirrhosis

What's Glycated Albumin (GA)? 2nd page Tests in Diabetes Since diabetes has no subjective symptoms, clinical testing is essential for detection

and treatment of the disease.

Various clinical tests are employed in the treatment of diabetes. The following tests

are representative examples.

For measuring glucose Urine glucose (first morning urine, postprandial urine, 24-hour urine, and casual urine) 

Blood glucose (fasting blood glucose, postprandial blood glucose, and casual blood glucose)

For diagnosing diabetes75-g Oral glucose tolerance test (blood glucose and insulin)(Insulin secretion status can also be determined)

For assessing glycemic control

Glycated hemoglobin (status for the previous 2 months) Glycated albumin (status for the previous 3 weeks)

Other biochemical tests

Cholesterol Triglycerides Lipoproteins Blood urea nitrogen (BUN) Creatinine Urea acid (UA)

Confirming Diabetes Treatment Efficacy Because glycated albumin rapidly and markedly reflects changes in mean blood

glucose, the measurement of glycated albumin is well suited for assessing treatment

regimens as well as evaluating treatment efficacy.

When an effective treatment regimen has been applied, improvement in the glycated

albumin value can generally be observed in about one week.

Clinical Tests for Confirming the Efficacy of Diabetes Treatment

Blood Glucose Test

Directly measures blood glucose at a single point in timeThe blood glucose test measures the amount of blood glucose at the time the blood sample is drawn. Blood glucose fluctuates depending on food intake, level of physical activity, and physical condition.

Glycated Albumin (GA) Test

Provides an index by which treatment efficacy can be evaluated and treatment regimens assessedThe GA test measures mean glycemic control over the previous three weeks.

Glycated Hemoglobin (HbA1c) Test

Assesses average glycemia over an extended time periodThe HbA1c test measures mean glycemic control over the previous two months. Short-or medium-term changes in average blood glucose cannot be suitably assessed with the HbA1c test.

The initial glycated albumin target should be a GA value of less than 20%.

The standard range for glycated albumin is 11% to 16%.

Target for Glycemic Control Patients should aim for a glycated albumin value of less than 20%.

(Unit: %)

  Excellent Good Acceptable Failure

GA < 18.0 18.1 to 21.0 21.1 to 24.0 24.1 <

Tahara Y. Glycoalbumin (GA). In: Shima K, editor.Kettou Wo Miru Kangaeru.Takyo: Nankodo; 2000. p62-69. (in Japan)

Is Glycated Albumin the Same as Fructosamine? In a word, no.

Fructosamine is a generic term referring to all glycated serum proteins, including

glycated albumin, in blood serum. Lucica® GA-L selectively measures glycated

albumin.

The fructosamine assay measures a total concentration of glycated serum proteins,

which can fluctuate due to 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 due to the concentrations of glycated and

non-glycated albumin.

Characteristics of Glycated Albumin POINT1 Serum albumin is a readily glycated protein. Glycated albumin (GA) is a glycation product of serum albumin.

Located in blood and throughout the body, albumin is a protein that bonds easily with

glucose.

Albumin glycates at four lysine (Lys) sites. 

Pablo Vidal, et al. 13th Int. Symposium on Column Liquid Chromatography, Stockholm, June 1989　

  Glycated albumin changes markedly.

GA values are approximately 3 times larger than their corresponding glycated

hemoglobin (HbA1c) values and reflect changes in blood glucose levels markedly.

Changes in glycated albumin (GA) and glycated hemoglobin (HbA1c) values during SU + α-GI treatment

Combination therapy with a sulfonylurea* (SU) and an α-glucosidase inhibitor** (α-GI) was administered to 16 outpatients

with type 2 diabetes.

With the use of glycated albumin (GA) as an indicator, the dose of the sulfonylurea was adjusted to achieve effective

treatment.

 

Mean patient data (n=16)

  Before treatment 12 weeks later

Blood glucose (mg/dl) 2 hours after breakfast 166±28 123±27

Serum IRI (μU/ml) 2 hours after breakfast 23.3±13.0 19.4±8.8

SU dose (mg) 64±35 48±31

*SU: gliclazide **α-GI: acarbose or voglibose

Ryuzo Kawamori, Juntendo University School of MedicineDiabetes 39:527-529 (1996)

POINT2　Glycated albumin levels reflect more immediate blood glucose status.

Since the half-life of albumin is short, glycated albumin (GA) mainly reflects the

average blood glucose value over the previous 2 weeks.

  Measurement of glycated albumin can confirm changes in blood glucose status 1 to 2

weeks after the commencement of treatment.Blood glucose status can be more accurately assessed in a monthly interval with the measurement of glycated albumin than with the measurement of glycated hemoglobin.

GA rapidly confirms treatment efficacy.

Shigeki Endo, Shizuoka Saiseikai General HospitalShizusai Ishi, 13(1): 23-35 (1997) (in Japanese)

Reagent Features and Performance

Overview

Lucica® GA-L is supplied as a ready-to-use, liquid reagent kit, for the measurement of

glycated albumin, which:

contains high-specificity protease and enzymes, and

can be utilized with general biochemical automated analyzers, and

delivers same-visit results prior to physician consultation, and

employs a novel BCP method that is highly specific to albumin.

Assay Principle

Glycated albumin: Influence by endogenous glycated amino acids is avoided through

the use of an elimination reaction.

Albumin: A novel BCP method permits more specific measurement of albumin.

Calculation of glycated albumin (GA) value

Kouzuma T, et al. Clinical Chimica Acta 346:135-143 (2004)

Assay Precision

Intra-day reproducibility (n = 20)

  Control Normal sera Diabetic sera

Mean 14.4% 15.9% 24.5%

SD 0.09 0.13 0.23

CV 0.63% 0.82% 0.93%

Inter-day reproducibility (n = 20)

  Normal sera Diabetic sera

Mean 16.2% 24.8%

SD 0.091 0.166

CV 0.56% 0.67%

Reduced Frequency of Calibration

  Normal sera Diabetic sera

Mean 15.9% 24.3%

SD 0.109 0.182

CV 0.68% 0.75%

A CV of less than 1% was attained even though calibration was conducted only on the first day of a two-week period of assays.

Interfering Substances

Bilirubin F interference

Chyle interference

Ascorbic acid interference

Bilirubin C interference

Glucose interference

Hemoglobin interference

 

Bilirubin F and C, chyle, and glucose demonstrated almost no interference in the glycated albumin (GA) assay.

Ascorbic acid up to 100 mg/dL and hemoglobin up to 196 mg/dL demonstrated no interference in the GA assay.

Hemoglobin demonstrated slightly negative interference.

Anti-coagulant/Glycolytic Inhibitor Interference

Linearity

Correlation

Assay Examples

Glycated Albumin Reagents

Albumin Reagents

Assessment of Glycemic Control

Glycated albumin (GA) values are about 3 times greater than glycated hemoglobin

(HbA1c) values when glycemic control is stable.

  Excellent Good Acceptable Failure

GA < 18.0 18.1 to 21.0 21.1 to 24.0 24.1 <

Tahara Y. Glycoalbumin (GA). In: Shima K, editor.Kettou Wo Miru Kangaeru.Takyo: Nankodo; 2000. p62-69. (in Japan

Glycated Hemoglobin or Glycated Albumin for Assessment of Glycemic Control in

Hemodialysis Patients With Diabetes?

Masanori Abe, Koichi Matsumoto

Nat Clin Pract Nephrol. 2008;4(9):482-483. 

This commentary discusses the findings of a study by Peacock et al., who measured levels of

glycated hemoglobin (HbA1c) and glycated albumin in patients with diabetes who either were

or were not on hemodialysis in an effort to determine which marker is the better indicator of

glycemic control. They found that HbA1c and glycated albumin levels are both independently

associated with serum glucose level. However, HbA1c level -- unlike glycated albumin level

-- was also influenced by hemodialysis, hemoglobin level, and erythropoietin dose. Although

we agree that glycated albumin level could be a better indicator of glycemic control than

HbA1c level in patients on hemodialysis who have diabetes and anuria, this conclusion might

not be applicable to patients with massive proteinuria or to those on peritoneal dialysis.

Further studies are required to confirm the target glycated albumin level that is necessary to

ensure a good prognosis for patients with diabetes who are on hemodialysis because no clear

consensus has yet been reached. In addition, more data are needed to determine at which

stage of kidney disease measurement of glycated albumin levels becomes preferable to

assessment of HbA1c level.

In patients with diabetes, strict glycemic control lowers the risk of cardiovascular events --

which are the main cause of death in this setting[1] -- and improves prognosis among those

with chronic kidney disease (CKD) who undergo regular hemodialysis;[2]therefore, the

accurate assessment of glycemic control is important to optimize outcomes.

Glycated hemoglobin (HbA1c) level, which indicates the percentage of circulating

hemoglobin that has chemically reacted with glucose, reflects the blood glucose level over

the 120 days preceding the test; glucose levels during the 30 days before the test have the

biggest impact on HbA1c level. The lack of specific guidelines for assessing glycemic control

in patients who are receiving hemodialysis has resulted in the HbA1c assay -- which is widely

used in the general population -- being the test of choice in this setting. However, in patients

with diabetes who are on hemodialysis, factors such as anemia (due to reduced erythrocyte

life span or iron deficiency), recent transfusions, metabolic acidosis, and administration of

erythropoietin affect the accuracy of the HbA1c assay.[3] By increasing the proportion of

young erythrocytes in the blood, both anemia and erythropoietin can falsely lower

HbA1c levels, which could in turn lead to a failure to diagnose hyperglycemia.

[4] Approximately 90% of patients on hemodialysis worldwide undergo erythropoietin

treatment;[5] therefore, HbA1c might be an unsuitable marker for glycemic control in the

hemodialysis setting.

On the basis of a study involving Japanese patients on hemodialysis, [3] glycated albumin has

been proposed to be a better marker of glycemic control than HbA1c, as levels of glycated

albumin in the blood are unaffected by changes in the survival time of erythrocytes.

Peacock et al. have now sought to validate the measurement of glycated albumin as an

alternative to HbA1cquantification for the assessment of glycemic control in 307 American

patients with diabetes, of whom 258 were undergoing hemodialysis and 49 did not have overt

kidney disease.[6] To quantify the level of glycated albumin, Peacock et al. utilized a new

enzymatic assay that relies on an albumin-specific proteinase and, unlike the conventional

assay, is not subject to interference by endogenous glycated amino acids or changes in

albumin concentration.

Multiple regression analysis confirmed that both HbA1c and glycated albumin levels were

independently associated with serum glucose concentration (P <0.0001 for both). However,

Peacock et al. found that the glycated-albumin:HbA1c ratio was higher in the patients on

hemodialysis than in the patients without kidney disease (2.72 vs 2.07; P <0.0001). Thus, in

patients on hemodialysis, HbA1c measurements significantly underestimate blood glucose

levels compared with glycated albumin values. In addition, HbA1c values were independently

associated with hemodialysis (P <0.0001) and, in hemodialysis patients, with hemoglobin

concentration (P = 0.0027) and erythropoietin dose (P = 0.03). By contrast, glycated albumin

level was not significantly associated with hemodialysis, or with hemoglobin level or

erythropoietin dose in patients on hemodialysis; therefore, the authors concluded that

glycated albumin is a better indicator of glycemic control than HbA1c.

The average glycated-albumin:HbA1c ratio in the patients on hemodialysis in Peacock et al.'s

study was slightly lower than that reported by Inaba et al. for the Japanese patients who were

receiving hemodialysis (2.72 vs 3.81).[3] This inconsistency might be due to differences

between the two studies in the serum albumin assays used, the erythropoietin doses

administered, the mean HbA1c levels, or the patients' ethnicity. The mean erythropoietin dose

given to the American patients on hemodialysis far exceeded that administered to their

Japanese counterparts (22,876 U/week vs 5,385 U/week), and the mean HbA1c level in the

American patients on hemodialysis was higher than that in the Japanese participants (6.8% vs

5.85%). The contention by Peacock et al. that discrepancies between the two studies might be

due to the large proportion of African Americans (63.6% of the hemodialysis population) in

the US study is difficult to understand. African Americans have an increased risk of carrying

the hemoglobin S and thalassemia genes, which are both associated with decreased

erythrocyte survival and would, thus, be expected to increase, rather than decrease, the

glycated-albumin:HbA1c ratio.

Some issues remain to be clarified. In Peacock et al.'s study, glycated albumin values were

measured only once. Measurement of glycated albumin level reflects glycemic control for

only the 1-2 weeks preceding the assay, so repeated measurements of glycated albumin (i.e.

every 2 weeks or monthly) will be required in future studies. Furthermore, it will be

important to determine the clinical stage at which these measurements should be initiated (i.e.

at CKD stage 3, 4, or 5, at diagnosis of renal anemia, or upon initiation of erythropoietin

therapy). The use of glycated albumin levels to assess glycemic control might be limited to

patients with anuria or normoalbuminuria who are receiving hemodialysis. In patients on

peritoneal dialysis and those with CKD who have massive proteinuria, glycated albumin

levels can be falsely reduced because of the shorter exposure time of albumin to glucose in

plasma. Further investigations are also required to establish the target glycated albumin level

that predicts the best prognosis for patients with diabetes who are on hemodialysis.

Moreover, no long-term, large-scale clinical trials have investigated the use of glycated

albumin as an indicator of glycemic control. Thus, whether this parameter is an accurate

predictor of morbidity and mortality in patients with diabetes who are on hemodialysis

remains to be ascertained.

In patients with diabetes who are on hemodialysis, glycated albumin level seems to reflect

glycemic control more accurately than does glycated hemoglobin level. However, clinicians

should be aware that optimal levels of glycated albumin have not yet been established and

that whether glycated albumin levels reflect glycemic control in patients with proteinuria and

in those undergoing peritoneal dialysis is unclear.

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References

1. Gaede P et al. (2003) Multifactorial intervention and cardiovascular disease in

patients with type 2 diabetes. N Engl J Med 348: 383-393

2. Morioka T et al. (2001) Glycemic control is a predictor of survival for diabetic

patients on hemodialysis. Diabetes Care24: 909-913

3. Inaba M et al. (2007) Glycated albumin is a better glycemic indicator than glycated

hemoglobin values in hemodialysis patients with diabetes: effect of anemia and

erythropoietin injection. J Am Soc Nephrol 18: 896-903

4. Joy MS et al. (2002) Long-term glycemic control measurements in diabetic patients

receiving hemodialysis. Am J Kidney Dis 39: 297-307

5. Pisoni RL et al. (2004) Anemia management and outcomes from 12 countries in the

Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 44: 94-

111

6. Peacock TP et al. (2008) Comparison of glycated albumin and hemoglobin A1c levels

in diabetic subjects on hemodialysis. Kidney Int 73: 1062-1068

 

Reprint Address

Masanori Abe, Division of Nephrology, Hypertension and Endocrinology, Department of

Medicine, Nihon University School of Medicine, 30-1, Oyaguchi-Kamimachi, Itabashi-ku,

Tokyo 173-8610, Japan; Email: mabe@med.nihon-u.ac.jp

Nat Clin Pract Nephrol. 2008;4(9):482-483. © 2008  Nature Publishing Group

Chin Med J (Engl). 2013;126(17):3295-300.

Glycated albumin may be a choice, but not an alternative marker of glycated hemoglobin for glycemic control assessment in diabetic patients undergoing maintenance hemodialysis.Chen FK1, Sun XF, Zhang D, Cui SY, Chen XM, Wei RB, Lu JM, Li JJ, Liu WH, Zhang DL, Zhang ZM.

Author informationAbstractBACKGROUND:

It has been suggested that glycated hemoglobin (HbA1c) underestimate the actual glycemic control levels in maintenance

hemodialysis (MHD) patients, because of anemia and the using of erythropoietin (EPO); it was recommended that glycated

albumin (GA) should be an alternative marker. Therefore, the assessment performances of glycemic control were compared

between GA and HbA1c in this research by referring to mean plasma glucose (MPG) in diabetes mellitus (DM) patients

undergoing MHD or not.

METHODS:

MPG was calculated according to the data registered at enrollment and follow-up 2 months later and corresponding HbA1c,

albumin (ALB), GA, etc. were measured in 280 cases. A case-control study for comparing GA and HbA1c was done among the

groups of MHD patients with DM (n=88) and without DM (NDM; n=90), and non-MHD ones with DM (n=102) using MPG for an

actual glycemic control standard.

RESULTS:

In these 3 groups, only for DM patients' (whether undergoing MHD or not), GA and HbA1c correlated with MPG significantly (P

< 0.01). Through linear regression analysis, it could be found that the regression curves of GA almost coincided in MHD and

non-MHD patients with DM, because the intercepts (2.418 vs. 2.329) and slopes (0.053 vs. 0.057) were very close to each

other. On the contrary, regression curves of HbA1c did not coincide in the two groups, because variance of the slopes (0.036

vs. 0.052) were relatively large. Through comparing receiver operating characteristic (ROC) areas under the curve (AUC), it

could be understood that the assessment performances of GA and HbA1c in MHD patients were lower than those in non-MHD

ones, and assessment performance of HbA1c in MHD patients was better than GA (P < 0.05). In addition, the effects of Hb and

EPO dose on HbA1c, or that of ALB on GA were unobvious in our study.

CONCLUSIONS:

Actual glycemic control level in MHD patients with DM may be underestimated by HbA1c, and it could be avoided by GA;

however, glycemic evaluating performance of HbA1c may be still better than that of GA. Therefore, HbA1c should not be

replaced completely although GA can be used as a choice to monitor glycemic level

Rinsho Byori. 2014 Jan;62(1):45-52.

[Indicators of glycemic control --hemoglobin A1c (HbA1c), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG)].[Article in Japanese]

Sato A.

AbstractThe clinical goal of diabetes management is a good quality of life that is not different from that of a healthy subjects. To fulfill

the goal, prevention of complications is needed under good glycemic control. Although blood glucose measurement is essential

for glycemic control, there are diurnal variations in blood glucose levels. An indicator of long-term glycemic control is necessary.

HbA1c is the gold standard measurement for the assessment of glycemic control, and worldwide large scale clinical studies of

diabetes complications have greatly valued HbA1c as an indicator of glycemic control. In addition, recently, HbA1c was

recommended for use in the diagnosis of diabetes in Japan and in the United States. Although HbA1c is used widely and

internationally, international standardization of the HbA1c value has not been achieved. In Japan, from April 2014, it has been

decided to adopt the National Glycohemoglobin Standardization Program (NGSP) value, which is used by many countries

globally, as the first step toward internationalization. Recently, cardiovascular disease in diabetic patients has been increasing

in Japan. Relationships between postprandial hyperglycemia and cardiovascular disease have been noted. Therefore, the

correction of postprandial hyperglycemia is one of the important goals of glycemic control to prevent cardiovascular disease.

HbA1c or glycated albumin (GA) results from the glycation of hemoglobin or serum albumin and represents 2-month or 2-week

glycemia, respectively. In addition, the glycation speed of GA is ten times faster than HbA1c, so GA is likely to reflect the

variation in blood glucose and postprandial hyperglycemia in combination with HbA1c and its value. 1,5-anhydroglucitol (AG) is

a marker of glycemia-induced glycosuria, since reabsorption of filtered 1,5-AG in the proximal tubule is competitively inhibited

by glucose. It is an indicator to identify rapid changes in hyperglycemia. Understanding the characteristics of the indicators

above, it is important to use them suitably for each diabetes subject and to recognize glycemic control conditions more

accurately.