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Diabetes Prevention
Other factors influencing accuracy and the comparability between used by physicians in the office setting to monitor the long-term
glucose meter and central laboratory results include external factors glycemic status of patients. HbA
1c
is expressed as the percentage of
such as environmental effects, the patient’s general health status, and hemoglobin that is glycosylated. It is formed non-enzymatically by the
interference from other substances. Environmental effects refer to exposure of hemoglobin to glucose. Once a hemoglobin molecule is
factors that influence the glucometer and/or test strips prior to or during glycosylated, it remains glycosylated until the red blood cell is destroyed
use. Light, temperature, humidity, and air exposure can all affect the test and hemoglobin is metabolized. HbA
1c
therefore reflects the average
strips and alter the stability of the delicate enzymes and reagents level of glucose to which the cell was exposed during its life-cycle
contained within the test strips.
15
Exposure of test strips and meters to (approximately 120 days or four months).
16,17
environmental extremes in cars, at the gym, or during transport can
compromise results. The patient’s general health status also plays an In 2008, a new study relating HbA
1c
to blood glucose levels was
important role. Circulatory problems can lead to capillary specimens that published. The A1c-Derived Average Glucose (ADAG) study analyzed
do not reflect central venous levels. Alterations in fasting status, oxygen data from 507 patients with type 1 and type 2 diabetes as well as
therapy, pH, or hematocrit can all interfere with analysis.
15
Chemical patients without diabetes from 10 centers in the US, Europe, and Africa.
interferences can occur from the presence of maltose, ascorbic acid, For three months, each participant performed three types of multipoint
salicylate, and other drugs. Maltose is a common problem in the inpatient self-monitoring measurement, which resulted in 2,700 blood glucose
setting as it is frequently used in various parenteral substances. Maltose tests per participating subject. The patients also had HbA
1c
levels drawn
can cross-react with some POC glucose meters, leading to falsely at baseline and monthly for three months. The authors extrapolated a
elevated results and the potential to overdose required insulin. Ascorbic simple formula to calculate an estimated average glucose (eAG) level
acid and salicylates can act as alternate electron carriers
15
and also affect from measured HbA
1c
percentages
16
based on the study data. This
the enzymatic processes within the strip. equation enables physicians to explain long-term glycemic status to
patients in the familiar terms of glucose levels in mg/dl or mmol/l rather
Another major factor causing differences between glucose meter and than HbA
1c
in units of percent total hemoglobin.
core laboratory results is the type of specimen used for analysis. Most
laboratory methods analyze plasma, while POC devices analyze whole While this relationship and calculation can greatly enhance physician–
blood.
15
Core laboratories receive whole-blood specimens from which patient communication, its value in the setting of diagnosis is not yet
they separate the cells and utilize the plasma portion for analysis. When established. The study itself has a number of limitations pertaining both
using a glucose meter, a drop of the patient’s (whole) blood is applied to to the HbA
1c
assay itself and to study parameters. HbA
1c
can be
the glucose test strip. The blood diffuses through multiple layers of artificially lowered if a patient is in a chronic hemolytic state and
absorbent materials that filter out erythrocytes allowing the plasma to therefore has shortened red cell survival. The HbA
1c
can also be falsely
diffuse though to the enzyme reagents in the strip.
15
There is commonly elevated if the patient has prolonged red cell survival, such as after
an 11% difference between whole-blood glucose and results from splenectomy. Additionally, HbA
1c
can be formed only if a patient has
plasma methods that is largely attributed to the relationship of glucose normal hemoglobin, excluding patients with sickle cell disease or
to water. Glucose diffuses freely in the water space of whole blood. various forms of thalassemia.
17
The study only included six centers in the
However, erythrocytes contain less water (per unit volume) than plasma US, three in Europe, and one in Cameroon. Another center in Asia was
and therefore whole-blood results are lower than plasma results at any eliminated from the data due to improper specimen storage.
glucose concentration.
15
This relationship makes glucose meter results Participants were between 18 and 70 years of age, but did not include
dependent on hematocrit levels, since a higher erythrocyte mass will children or pregnant women.
16,17
The study was also limited in terms of
lead to greater differences. Most manufacturers attempt to normalize the number of ethnic groups with a high prevalence of diabetes, such as
the whole blood to plasma differences through calibration, using African-Americans, American-Indians and Eskimos. An argument could
normal volunteers to establish calibration settings. However, calibration be made as to whether these factors are relevant to the hemoglobin/
volunteers with normal hematocrits add additional biases when the average glucose relationship, since glucose–hemoglobin binding is non-
glucose meters are utilized on hospitalized patients with abnormal enzymatic. However, very little research has been undertaken on the
hematocrits. One POC glucose analyzer system currently on the market utility of HbA
1c
outside its traditional use in monitoring dietary and
aims to address this issue. The HemoCue Glucose 201 Analyzer uses lifestyle compliance and insulin management. All current treatment and
saponin in its proprietary cuvette technology to lyse red cells prior to diagnostic recommendations are based on the Diabetes Control
analysis. Using this technology enables the device to perform blood and Complications Trial (DCCT), which examined direct blood glucose
glucose analysis on whole blood rather than plasma.
15
However, this is levels, not HbA
1c
.
6,7,17
one of the few devices that still analyze whole blood. The majority of
glucose meters utilize methodologies that are heavily hematocrit- Just this year, the ADA commissioned an International Expert Committee
dependent. It is because of the increased variability of POCT results that on diabetes to re-examine the concept of HbA
1c
for the diagnosis of
the ADA continues to recommend the use of plasma glucose for the diabetes. Taking into consideration long-term glycemic levels and the
diagnosis of diabetes. timing of onset of diabetic complications, the committee was able to set
the diagnostic threshold for diabetes at an HbA
1c
percentage of ≥6.5%
Glycated Hemoglobin and a range of 6.0 to <6.5% for pre-diabetes. These numbers, while not
Another test that has recently been suggested for the diagnosis of being absolute dividing lines, are sufficiently sensitive and specific to
diabetes is the glycated hemoglobin (HbA
1c
) assay. Currently, HbA
1c
is identify individuals at risk for developing diabetic complications and could
24 US ENDOCRINOLOGY
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