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 diabetes

75-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 time

The 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 assessed
The GA test measures mean glycemic control over the
previous three weeks.

Glycated Hemoglobin
(HbA1c) Test

Assesses average glycemia over an extended time period

The 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

< 18.0

18.1 to 21.0

21.1 to 24.0

24.1 <

GA

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 + -GI treatment

Combination therapy with a sulfonylurea* (SU) and an -glucosidase inhibitor** (-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)

Blood glucose (mg/dl) 2 hours after breakfast

Serum IRI (U/ml) 2 hours after breakfast
SU dose (mg)

12 weeks later

16628

12327

23.313.0

19.48.8

6435

4831

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

Before treatment

Ryuzo Kawamori, Juntendo University School of Medicine

Diabetes 39:527-529 (1996)

POINT2Glycated 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 Hospital

Shizusai 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.

GA

Excellent

Good

Acceptable

Failure

< 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 (HbA 1c) 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 HbA 1c and glycated albumin levels are both
independently associated with serum glucose level. However, HbA 1c 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 HbA 1c 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 HbA 1c assay.
[3]

By increasing the proportion of young erythrocytes in the blood, both

anemia and erythropoietin can falsely lower HbA 1c 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 HbA 1c 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, HbA 1c 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 HbA 1c 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

proteinuria and in those undergoing peritoneal dialysis is unclear.

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with

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: 297307
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 information
Abstract
BACKGROUND:
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.

Abstract
The 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.