Glycosylated Haemoglobin – Essay Example

In case blood glucose level is well within control and gives stable results, the test is performed every six months intervals. The long-term or chronic complications of diabetes are those that characteristically occur after years of high blood sugar levels. These are diabetic macrovascular and microvascular diseases. The long term complications correlate well with A1c levels.(Web ref 2).
Wild and Bains (2004) cautioned clinical laboratories and point-of-care testing to be careful of the interferences produced in assays by variant Hbs. The majority arise from point mutations in the , , , or Hb chains. Herman et al (2007) also raised the important question of whether A1c can be used as a diagnostic test for diabetes detection and control in ethnic minorities whose mean A1c concentration vary significantly from whites. In the light of these observations the current project intends to analyse literature particularly on blood glucose tests, long term complications of high blood sugar and applicability of HbA1c test to ethnic diabetics.
Studies have shown that glycohaemoglobin values in the “better ranges” correlate with less incidences of diabetic complications later in life (Table 1; Fig 1 b). Type 1 diabetics will typically have hemoglobin A1c levels determined every 3 to 4 months, while Type 2 diabetics will require measurements less often (Web ref 3; Web ref 1). It so because Red blood cells are replaced in about 90 days thus test gives blood glucose levels for that period.Glycosylated Haemoglobin – Essay Example.  Normal blood glucose levels are below 6 percent HbA1c however these vary laboratory to laboratory (McCool and Woodruff 1999; Web ref 1) HbA1c levels compare well with blood glucose levels as shown below:
Table 1. Comparison of HbA1c test and Blood glucose levels (from McCool and Woodruff 1999)
HbA1c
Level of control
Blood glucose (mg/dl)
5 %
6%
7%
8%
9%
10%
11%
12%
Excellent
Excellent
Good
Acceptable
Poor
Poor
Poor
Poor
90 mg/dl
120 mg/dl
150 mg/dl
180 mg/dl
210 mg/dl
240 mg/dl
270 mg/dl
300 mg/dl
The rapid fluctuations in blood glucose that normally occur are smoothed out and the long-term level of glucose is now available to clinicians as a HbA1c test, because glycosylated hemoglobin has been shown to correlate with the integrated average blood consumption of glucose over the preceding six to eight weeks (Nathan 1990). Moreover, No preparation is necessary.
Fig1 b) Controlled and uncontrolled diabetes conditions. (from Web ref 1) Glycosylated Haemoglobin – Essay Example.
Controlled diabetes, less blood glucose results in less glycosylated haemoglobin
Uncontrolled diabetes, more blood glucose results in high glycosylated haemoglobin
HbA1c is also a reasonably sensitive test for gestational diabetes mellitus (GDM) which occurs in pregnant women. The test when conducted on pregnant women, it could pick up 87.1 cases of GDM successfully. The study gives a good alternative to OGTT (oral glucose tolerance test) which is inconvenient and requires fasting (Aldasouqi et al, 2008). The HbA1c test earlier done in laboratories only is now available in relatively economical home version as well (Web ref 4). The control of HbA1c and avoiding long term diabetic complications are discussed later.
Diabetes: An overview
The word ‘diabetes

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The term HbA1c refers to glycated hemoglobin. It develops when hemoglobin, a protein within red blood cells that carries oxygen throughout your body, joins with glucose in the blood, becoming ‘glycated’. Analysis of glycated hemoglobin (HbA1c) in blood provides evidence about an individual’s average blood glucose levels during the previous two to three months, which is the predicted half-life of red blood cells (RBCs). The HbA1c is now recommended as a standard for testing and monitoring diabetes.

Historically, HbA1c was first isolated by Huisman in 1958 and characterized by Bookchin and Gallop in 1968, as a glycoprotein. The elevated levels of HbA1c in diabetic patients were reported by Rahbar in 1969.Glycosylated Haemoglobin – Essay Example.  Bunn et al. identified the pathway leading to the formation of HbA1c in 1975. Using the HbA1c as a biomarker for monitoring the levels of glucose among diabetic patients was first proposed by Koenig et al. in 1976.

Proteins are frequently glycated during various enzymatic reactions when the conditions are physiologically favorable. However, in the case of hemoglobin, the glycation occurs by the nonenzymatic reaction between the glucose and the N-terminal end of the ß-chain, which forms a Schiff base. In the primary step of glycated hemoglobin formation, hemoglobin and the blood glucose interact to form aldimine in a reversible reaction. In the secondary step, which is irreversible, aldimine is gradually converted into the stable ketoamine form.

The major sites of hemoglobin glycosylation, in the order of prevalence, are ß-Val-1, ß-Lys-66, and a-Lys-61. Normal adult hemoglobin consists predominantly of HbA (a2ß2), HbA2 (a2d2), and HbF (a2?2) in the composition of 97%, 2.5%, and 0.5%, respectively. About 6% of total HbA is termed HbA1, which in turn is made up of HbA1a1, HbA1a2, HbA1b, and HbA1c fractions, defined by their electrophoretic and chromatographic properties. HbA1c is the most abundant of these fractions and in health comprises approximately 5% of the total HbA fraction.

As mentioned above, glucose in the open chain format binds to the N-terminal to form an aldimine before undergoing an Amadori rearrangement to form a more stable ketoamine. This is a nonenzymatic process that occurs continuously in vivo. The formation of the glycated hemoglobin is a normal part of the physiologic function cycle. Glycosylated Haemoglobin – Essay Example. However, as the average plasma glucose increases, so does the amount of glycated hemoglobin in the plasma. This specific characteristic of the hemoglobin biomarker is utilized for estimating the average blood glucose levels over the previous two to three months.

So, we have described the current trends in diabetes prevalence, diagnostic and prognostic potential of HbA1c, analytical aspects in HbA1c assays, and physiological changes due to hemoglobin glycation. Glycosylated Haemoglobin – Essay Example.