Glycosylated hemoglobin

Glycosylated (or glycated) hemoglobin ("hemoglobin A1c, Hb_1c , or Hb_A1c") 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. Glycosylation of hemoglobin has been implicated in nephropathy and retinopathy in diabetes mellitus. Monitoring the Hb_A1c in type-1 diabetic patients may improve treatment.cite journal |author=Larsen ML, Hørder M, Mogensen EF |title=Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus |journal=N. Engl. J. Med. |volume=323 |issue=15 |pages=1021–5 |year=1990 |pmid=2215560 |doi=]

History

Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column. [cite journal |author=Huisman TH, Martis EA, Dozy A |title=Chromatography of hemoglobin types on carboxymethylcellulose |journal=J. Lab. Clin. Med. |volume=52 |issue=2 |pages=312–27 |year=1958 |pmid=13564011 |doi=] It was first characterized as a glycoprotein by Bookchin and Gallop in 1968.cite journal |author=Bookchin RM, Gallop PM |title=Structure of hemoglobin A1c: nature of the N-terminal beta chain blocking group |journal=Biochem. Biophys. Res. Commun. |volume=32 |issue=1 |pages=86–93 |year=1968 |pmid=4874776 |doi=10.1016/0006-291X(68)90430-0] Its increase in diabetes was first described in 1969 by Samuel Rahbar and coworkerscite journal |author=Rahbar S, Blumenfeld O, Ranney HM |title=Studies of an unusual hemoglobin in patients with diabetes mellitus |journal=Biochem. Biophys. Res. Commun. |volume=36 |issue=5 |pages=838–43 |year=1969 |pmid=5808299 |doi=10.1016/0006-291X(69)90685-8] The reactions leading to its formation were characterized by Bunn and his co-workers in 1975.cite journal |author=Bunn HF, Haney DN, Gabbay KH, Gallop PM |title=Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c |journal=Biochem. Biophys. Res. Commun. |volume=67 |issue=1 |pages=103–9 |year=1975 |pmid=1201013 |doi=10.1016/0006-291X(75)90289-2] 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.cite journal |author=Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A |title=Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus |journal=N. Engl. J. Med. |volume=295 |issue=8 |pages=417–20 |year=1976 |pmid=934240 |doi=]

Underlying principle

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 Hb_A1c 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. [cite web |url=http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm |title=Hemoglobin A1c Fact Sheet |accessdate=2007-12-26 |work=Michigan Diabetes Research & Training Center ]

Measuring A1c

There are a number of techniques used to measure A1c.

Laboratories use :
* high-performance liquid chromatography (HPLC)
* Immunoassay

Point of care (eg doctors surgery) devices use :
* Immunoassay
* Boronate Affinity Chromatography

POC A1c tests are certified by the National Glycohemoglobin Standardization Program (NGSP)to standardise them against the results of the 1993 Diabetes Control and Complications Trial (DCCT) [http://www.devicelink.com/ivdt/archive/08/07/009.html Developing Point of care HbA1c tests for Diabetes monitoring] .

Interpretation of results

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.cite journal |author=Rohlfing C, Wiedmeyer HM, Little R, "et al" |title=Biological variation of glycohemoglobin |journal=Clin. Chem. |volume=48 |issue=7 |pages=1116–8 |year=2002 |pmid=12089188 |doi= |url=http://www.clinchem.org/cgi/content/full/48/7/1116] In general, the reference range (that found in healthy persons), is about 4%–5.9%. [cite web |url=http://www.medicinenet.com/hemoglobin_a1c_test/article.htm |title=Hemoglobin A1c Test |accessdate=2007-12-26 |work=MedicineNet.com ]

Higher levels of Hb_A1c 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 Hb_A1c values. A diabetic person with good glucose control has a Hb_A1c level that is close to or within the reference range. The International Diabetes Federation and American College of Endocrinology recommend Hb_A1c values below 6.5%, while American Diabetes Association recommends that the Hb_A1c be below 7.0% for most patients. A high Hb_A1c represents poor glucose control. Persistent elevations in blood sugar (and therefore Hb_A1c) 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 Hb_A1c 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 Hb_A1c values and average blood glucose measurements over the previous 4-12 weeks is shown in the table. [cite web |author=Bartol T |title=Comparison of Blood Glucose, HbA1c, and Fructosamine |url=http://www.healthyinfo.com/clinical/endo/dm/hga1c.test.shtml |date=December 1, 2000 |accessdate=2007-06-04 - gives a comparison chart and cites following source:
*]

Indications and use

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. That being said, fasting blood sugar tests are crucial in making treatment decisions. The American Diabetes Association guidelines are similar to others in advising that the glycosylated hemoglobin test be performed at least two times a year in patients with diabetes who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients with diabetes whose therapy has changed or who are not meeting glycemic goals. [cite journal |author=American Diabetes Association|title=Standards of medical care in diabetes--2007 |journal=Diabetes Care |volume=30 |issue=Suppl 1 |pages=S4–S41 |year=2007 |pmid=17192377 |doi=10.2337/dc07-S004]

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 genetic differences in the hemoglobin molecule (hemoglobinopathy) such as sickle cell disease and other conditions 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.

There is variation among laboratories and a lack of consensus on a diagnostic threshold for glycosolated hemoglobin. For these and other reasons, no medical organization recommends the use of this test alone to diagnose diabetes. Instead, fasting plasma glucose or an oral glucose tolerance test are used.

References

ee also

*Diabetes mellitus
*Hemoglobin

External links

* [http://diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse]
* [http://care.diabetesjournals.org/cgi/content/full/30/suppl_1/S4 American Diabetes Association Standards of Medical Care 2007]
* [http://www.medicinenet.com/hemoglobin_a1c_test/article.htm Hemoglobin A1c Test]
* [http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm MDRTC Hemoglobin A1C Fact Sheet]
* [http://www.pace-med-apps.com/a1ccalc.htm Simple Online A1c Calculator]
* [http://www.metrika.com/ Metrika: A1C test for professionals and consumers.]
* [http://www.appraisetests.com/ The Appraise Home A1c Kit is the easy, 'at home' accurate and affordable way to reduce risk.]
* [http://www.devicelink.com/ivdt/archive/08/07/009.html Developing Point of care HbA1c tests for Diabetes monitoring. Aug 2008] Discusses different test methods