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Hba1c Test

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HbA1c test

Factors that Interfere with HbA1c Measurement: Genetic variants (e.g. HbS trait, HbC trait),
elevated fetal hemoglobin (HbF) and chemically modified derivatives of hemoglobin (e.g.
carbamylated Hb in patients with renal failure) can affect the accuracy of HbA1c measurements.
The effects vary depending on the specific Hb variant or derivative and the specific HbA1c
method. Table 1 contains information for most of the commonly used current HbA1c methods
for the four most common Hb variants, elevated HbF and carbamylated Hb. Interferences from
less common Hb variants and derivatives are discussed in Bry, et al [1]. All entries in Table 1 are
based on published information. In addition, if a product insert indicates clearly that there is
inference from a particular factor, then the interference is entered as “yes” and the product insert
is cited. When selecting an assay method, laboratories should take into consideration
characteristics of the patient population served, (e.g. high prevalence of hemoglobinopathies or
renal failure).

Factors that affect interpretation of HbA1c Results: Any condition that shortens erythrocyte
survival or decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic
anemia) will falsely lower HbA1c test results regardless of the assay method used [2]. HbA1c
results from patients with HbSS, HbCC, and HbSC must be interpreted with caution given the
pathological processes, including anemia, increased red cell turnover, and transfusion
requirements, that adversely impact HbA1c as a marker of long-term glycemic control.
Alternative forms of testing such as glycated serum protein or glycated albumin should be
considered for these patients.

Iron deficiency anemia, a major public health problem in developing countries, is associated with
higher HbA1c and higher fructosamine [3]. Consistent with these observations, iron replacement
therapy lowers both HbA1c and fructosamine concentrations in diabetic and non-diabetic
individuals [3-5]. HbA1c , but not glycated albumin, is increased in late pregnancy in
nondiabetic individuals owing to iron deficiency [6]. Insight into the mechanism was recently
obtained by the observation that malondialdehyde, which is increased in patients with iron
deficiency anemia [3], enhances the glycation of hemoglobin [7]. Alternative measures of
glycemic assessment (e.g., glucose monitoring) must be used in the presence of significant iron
deficiency anemia, at least until the iron deficiency has been successfully treated.

Chronic renal failure develops in many diabetic patients. The role of glycemic control and the
value of HbA1c in diabetic subjects with renal disease are controversial. While interference from
carbamylated Hb can be evaluated, the role of renal anemia, erythropoietin intake, and other
factors in chronic renal failure is more difficult to evaluate. Recent reports suggest HbA1c
underestimates glycemic control in diabetic patients on dialysis and that glycated albumin is a
more robust indicator of glycemic control [8-11]. Further studies are needed to clarify the role of
HbA1c in diabetic patients with chronic renal failure.

he HbA1c test (hemoglobin A1c, glycosylated hemoglobin A1c,


glycohemoglobin A1c, or A1c test) is a lab test, which reveals average
blood glucose over a period of two to three months.
Specifically, it measures the number of glucose molecules attached to hemoglobin, a
substance in red blood cells 1. People who do not have diabetes generally have an HbA1c level
of less than 6 %. This means that less than 6 % of their hemoglobin molecules have glucose
permanently attached 2.
Based on the results of studies such as the Diabetes Control and Complications Trial (DCCT),
which showed that tight blood glucose control could reduce the risk of diabetic eye, kidney and
nerve disease, the American Diabetes Association (ADA) recommends that people with
diabetes try to keep their HbA1c level below 7% 3.
Underlying Principle:
In the normal 120-day life span of the red blood cell glucose molecules join hemoglobin,
forming glycosylated hemoglobin. In individuals with poorly controlled diabetes, increases in
the quantities of this glycosylated hemoglobin are noted. Once a hemoglobin molecule is
glycosylated, it remains that way. A buildup of glycosylated hemoglobin within the red cell
reflects the average level of glucose to which the cell has been exposed during its life cycle.
Measuring glycosylated haemoglobin assesses the effectiveness of therapy by monitoring long-
term serum glucose regulation4

Online Journal Pharmainfo.net 2008 March 21

The HbA1c level is proportional to average blood glucose concentration over the previous four
weeks to three months (some researches state that the major proportion of its value is related
to a rather short term period of two to four weeks). Hemoglobin is the oxygen-carrying
pigment that gives blood its red color and also the predominant protein in red blood cells.
About 90% of hemoglobin is hemoglobin A. (The "A" stands for adult type.) Although one
chemical component accounts for 92% of hemoglobin A, approximately 8% of hemoglobin A is
made up of minor components that are chemically slightly different. These minor components
include hemoglobin A1c, A1b, A1a1, and A1a2. Hemoglobin A1c (HbA1c) is a minor
component
of hemoglobin to which glucose is bound. HbA1c also is referred to as glycosylated or
glucosylated hemoglobin 5.
HbA1c levels depend on the blood glucose concentration. That is, the higher the glucose
concentration in blood, the higher the level of HbA1c; and not influenced by daily fluctuations
in the blood glucose concentration but reflect the average glucose levels over the prior six to
eight weeks. Therefore, HbA1c is a useful indicator of how well the blood glucose level has
been controlled in the recent past and may be used to monitor the effects of diet, exercise and
drug therapy on blood glucose in diabetic patients 6.
Healthy HbA1c levels 7:
However target HbA1c levels may vary from person to person. A general range for HbA1c
levels is:
•Less than or equal to 7% is a very healthy HbA1c level
•Between 7% and 8% is a fair HbA1c level and needs work to improve
•Between 8% and 10% indicates your blood glucose levels are too high
•Above 10% indicates your blood glucose levels are extremely high

Online Journal Pharmainfo.net 2008 March 21


suggest that your treatment plan needs modifying; if you have Type 2 diabetes. Finally, HbA1c
tests are often used in setting and achieving treatment goals.
A major study, the UKPDS Study 8 published in 2000, managed to quantify many of the
benefits of reducing a high HbA1c level by just 1%.
•A 16% decrease in risk of heart failure
•A 14% decrease in risk of fatal or nonfatal myocardial infarction (heart attack)
•A 12% decrease in risk of fatal or nonfatal stroke
•A 21% decrease in risk of diabetes-related death
•A 14% decrease in risk of death from all causes
•A 43% decrease in risk of amputation
A 37% decrease in risk of small blood vessel disease (e.g. retinal blood vessel disease causing
vision loss).
Diabetic patients who are on oral antihyperglycemic agents should check their HbA1c once a
month. If it is high, patient should change diet and or doctor should change medication of the
patient. When the HbA1c is normal, everything is deemed right. The postprandial blood glucose
level monitoring was declared a new target for optimizing treatment of diabetes mellitus. But
HbA1c determination is the best method of monitoring of long term glucose control 9.

Since HbA1c is not influenced by daily fluctuations in blood glucose concentration, it cannot be
used to monitor day-to-day blood glucose concentrations and is inappropriate to be used for
adjusting insulin doses; nor can it detect the day-to-day presence or absence of hyperglycemia or
hypoglycemia. HbA1c may be increased falsely in certain medical conditions. These conditions
include

 kidney failure (uremia),


 chronic excessive alcohol intake,
 hypertriglyceridemia.

Medical conditions that may falsely decrease HbA1c include

 acute or chronic blood loss,


 sickle cell disease,
 thalassemia.

Nevertheless, patients should aim for the best level of glucose control they can achieve without placing
themselves at undue risk for hypoglycemia or other hazards associated with tight control (see question
3). Any improvement in blood glucose control has been shown to slow the development and
progression of microvascular complications.

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