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Glycosylated hemoglobin
From Wikipedia, the free encyclopedia
Glycosylated (or glycated) hemoglobin (hemoglobin A1c, Hb1c , HbA1c or HgA1c) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. Its name is sometimes abbreviated to A1C. It is formed in a non-enzymatic pathway by hemoglobin's normal exposure to high plasma levels of glucose. Glycation of hemoglobin has been implicated in nephropathy and retinopathy in diabetes mellitus. Monitoring the HbA1c in diabetic patients may improve treatment.[1]
| Diabetes mellitus
|
|---|
| Types of Diabetes |
| Diabetes mellitus type 1 Diabetes mellitus type 2 Gestational diabetes Pre-diabetes: |
| Disease Management |
| Diabetes management: •Diabetic diet •Anti-diabetic drugs •Conventional insulinotherapy •Intensive insulinotherapy |
| Other Concerns |
| Cardiovascular disease
Diabetic comas: Diabetic myonecrosis |
| Blood tests |
| Blood sugar Fructosamine Glucose tolerance test Glycosylated hemoglobin |
Contents |
Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column[2]. It was first characterized as a glycoprotein by Bookchin and Gallop in 1968[3]. Its increase in diabetes was first described in 1969 by Rahbar and coworkers[4] The reactions leading to its formation were characterized by Bunn and coworkers in 1975[5]. The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Koenig and coworkers[6].
In the normal 120-day life span of the red blood cell, glucose molecules join hemoglobin, forming glycated hemoglobin. In individuals with poorly controlled diabetes, increases in the quantities of these glycated hemoglobins are noted.
Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell reflects the average level of glucose to which the cell has been exposed during its life cycle. Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. (Some researchers state that the major proportion of its value is related to a rather short term period of two to four weeks [1].)
Laboratory results may differ depending on the analytical technique, the age of the subject, and biological variation among individuals. Two individuals with the same average blood sugar can have A1C values that differ by as much as 1 percentage point).[7] In general, the reference range (that found in healthy persons), is about 4%–5.9%.[2].
Higher levels of HbA1c are found in people with persistently elevated blood sugar, as in diabetes mellitus. While diabetic patient treatment goals vary, many include a target range of HbA1c values. A diabetic person with good glucose control has a HbA1c level that is close to or within the reference range. The International Diabetes Federation and American College of Endocrinology recommend HbA1c values below 6.5%, while American Diabetes Association recommends that the HbA1c be below 7.0% for most patients. A high HbA1c represents poor glucose control. Persistent elevations in blood sugar (and therefore HbA1c) increase the risk for the long-term vascular complications of diabetes such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness, erectile dysfunction, neuropathy (loss of sensation, especially in the feet), gangrene, and gastroparesis (slowed emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery such as poor wound healing.
Lower than expected levels of HbA1c can be seen in people with shortened red blood cell life span, such as with glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, or any other condition causing premature red blood cell death. Conversely, higher than expected levels can be seen in people with a longer red blood cell life span, such as with Vitamin B12 or folate deficiency.
The approximate mapping between HbA1c values and average blood glucose measurements over the previous 4-12 weeks is shown in the table.[8]
| HbA1c (%) |
Avg. Blood Sugar | |
|---|---|---|
| (mmol/L) | (mg/dL) | |
| 4 | 3.3 | 60 |
| 5 | 5.0 | 90 |
| 6 | 6.7 | 135 |
| 7 | 8.3 | 170 |
| 8 | 10.0 | 205 |
| 9 | 11.7 | 240 |
| 10 | 13.3 | 275 |
| 11 | 15.0 | 310 |
| 12 | 16.7 | 345 |
| 13 | 18.3 | 380 |
| 14 | 20.0 | 415 |
Glycosylated hemoglobin is recommended for both (a) checking blood sugar control in people who might be pre-diabetic and (b) monitoring blood sugar control in patients with more elevated levels, termed diabetes mellitus. For a single blood sample, it provides far more revealing information on glycemic behavior than a fasting blood sugar value, the more commonly performed test. The American Diabetes Association guidelines are similar to others in advising that the test be performed at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients whose therapy has changed or who are not meeting glycemic goals [9].
Glycosylated hemoglobin measurement is not appropriate where there has been a change in diet or treatment within 6 weeks. Likewise the test assumes a normal red blood cell aging process and mix of hemoglobin subtypes (predominantly HbA in normal adults). Hence people with recent blood loss or hemolytic anemia, or hemoglobinopathy such as sickle cell disease are not suitable for this test. The alternative fructosamine test may be used in these circumstances and it similarly reflects an average of blood glucose levels over the preceding 2 to 3 weeks.
Because of variation among laboratories and a lack of consensus on a diagnostic threshold, glycosolated hemoglobin is not recommended for use as a screening test to detect diabetes in patients with neither a prior diagnosis nor symptoms suggestive of the disease. For diagnosis, fasting plasma glucose or an oral glucose tolerance test is preferred.
- ^ Larsen ML, Hørder M, Mogensen EF (1990). "Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus". N. Engl. J. Med. 323 (15): 1021-5. PMID 2215560.
- ^ Huisman TH, Martis EA, Dozy A (1958). "Chromatography of hemoglobin types on carboxymethylcellulose". J. Lab. Clin. Med. 52 (2): 312–27. PMID 13564011.
- ^ Bookchin RM, Gallop PM (1968). "Structure of hemoglobin A1c: nature of the N-terminal beta chain blocking group". Biochem. Biophys. Res. Commun. 32 (1): 86–93. PMID 4874776.
- ^ Rahbar S, Blumenfeld O, Ranney HM (1969). "Studies of an unusual hemoglobin in patients with diabetes mellitus". Biochem. Biophys. Res. Commun. 36 (5): 838–43. PMID 5808299.
- ^ Bunn HF, Haney DN, Gabbay KH, Gallop PM (1975). "Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c". Biochem. Biophys. Res. Commun. 67 (1): 103–9. PMID 1201013.
- ^ Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976). "Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus". N. Engl. J. Med. 295 (8): 417-20. PMID 934240.
- ^ Rohlfing C, Wiedmeyer HM, Little R, et al (2002). "Biological variation of glycohemoglobin". Clin. Chem. 48 (7): 1116-8. PMID 12089188.
- ^ Bartol T (December 1, 2000). Comparison of Blood Glucose, HbA1c, and Fructosamine. Retrieved on 2007-06-04. - gives a comparison chart and cites following source:
- Nathan DM, Singer DE, Hurxthal K, Goodson JD (1984). "The clinical information value of the glycosylated hemoglobin assay". N. Engl. J. Med. 310 (6): 341-6. PMID 6690962.
- ^ American Diabetes Association (2007). "Standards of medical care in diabetes--2007". Diabetes Care 30 (Suppl 1): S4-S41. PMID 17192377.