Search
Search titles only
By:
Search titles only
By:
Home
Forums
New posts
Search forums
What's new
New posts
New profile posts
Latest activity
Members
Current visitors
New profile posts
Search profile posts
Log in
Register
Search
Search titles only
By:
Search titles only
By:
New posts
Search forums
Menu
Install the app
Install
Reply to Thread
Guest, we'd love to know what you think about the forum! Take the
Diabetes Forum Survey 2024 »
Home
Forums
Diabetes Discussion
Diabetes Discussions
HbA1c represents a 4 week average?
JavaScript is disabled. For a better experience, please enable JavaScript in your browser before proceeding.
You are using an out of date browser. It may not display this or other websites correctly.
You should upgrade or use an
alternative browser
.
Message
<blockquote data-quote="reidpj" data-source="post: 233636" data-attributes="member: 36922"><p>Hi All</p><p></p><p>"The longer estimate [3-4 months] is based on the assumption that the conversion of hemoglobin A to HbA1c is essentially irreversible. This was a reasonable assumption before the reaction rates were actually measured". See below:</p><p></p><p></p><p><em>Charly Coughran</em></p><p><em><a href="mailto:ccoughran@DELETE-TO-RESPOND-UCSD.EDU">ccoughran@DELETE-TO-RESPOND-UCSD.EDU</a> </em></p><p><em></em></p><p><em>Subject: What's HbA1c and what's it mean?</em></p><p><em></em></p><p><em>Hb = hemoglobin, the compound in the red blood cells that transports oxygen. Hemoglobin occurs in several variants; the one which composes about 90% of the total is known as hemoglobin A. A1c is a specific subtype of hemoglobin A. The 1 is actually a subscript to the A, and the c is a subscript to the 1. "Hemoglobin" is also spelled "haemoglobin", depending on your geographic allegiance.</em></p><p><em></em></p><p><em><strong>Glucose binds slowly to hemoglobin A, forming the A1c subtype. The reverse reaction, or decomposition, proceeds relatively slowly, so any buildup persists for roughly 4 weeks. Because of the reverse reaction, the actual HbA1c level is strongly weighted toward the present. Some of the HbA1c is also removed when erythrocytes (red blood cells) are recycled after their normal lifetime of about 90-120 days. These factors combine so that the HbA1c level represents the average bGlevel of approximately the past 4 weeks, strongly weighted toward the most recent 2 weeks. It is almost entirely insensitive to bG levels more than 4 weeks previous.</strong></em></p><p><em></em></p><p><em>In non-diabetic persons, the formation, decomposition and destruction of HbA1c reach a steady state with about 3.0% to 6.5% of the hemoglobin being the A1c subtype. Most diabetic individuals have a higher average bG level than non-diabetics, resulting in a higher HbA1c level. The actual HbA1c level can be used as an indicator of the average recent bG level. This in turn indicates the possible level of glycation damage to tissues, and thus of diabetic complications, if continued for years.</em></p><p><em></em></p><p><em>Interpreting HbA1c values can be tricky for several reasons. See the</em></p><p><em>following section for more details.</em></p><p><em></em></p><p><em></em></p><p><em>Subject: Why is interpreting HbA1c values tricky?</em></p><p><em></em></p><p><em>Interpreting HbA1c values is tricky for several reasons: differing lab measurements, variation among individuals, and misapprehension of the relevant timeframe.</em></p><p><em></em></p><p><em>First trick: several different lab measurements have been introduced since 1980, measuring slightly different subtypes with different</em></p><p><em>limits for normal values and thus different interpretive scales.</em></p><p><em></em></p><p><em>A National Glycohemoglobin Standardization Program began in 1996, sponsored by the American Diabetes Association and others. See reference 1. This program certifies HbA1c assays which conform to the method used in the DCCT. However, as of 1998 other versions are still in use in many places, both in the US and elsewhere. When you get a lab result, be sure to look at what the lab considers to be the normal range. Most discussion of HbA1c values in m.h.d appears to be based on the DCCT, where the normal range is approximately 3.0-6.1%. Caveat lector. (See part 5, Research, of this FAQ for more information on the DCCT, the Diabetes Control and Complications Trial.)</em></p><p><em></em></p><p><em>Second trick: HbA1c levels appear to vary by up to 1.0% among individuals with the same average bG. See reference 2.</em></p><p><em></em></p><p><em>This is very recent research and its implications are not yet clear. The actual reaction rates governing the formation of HbA1c may vary among individuals. Some of the variation may be due to differences in erythrocyte (red blood cell) survival times -- the rough 90-120 day range noted earlier -- although other work limits this to a small part of the total variation (see reference 5). Variations in the HbA1c formation rate may or may not correlate with the rate of damage to other tissues.</em></p><p><em></em></p><p><em>While we await further research, we can only say that differences of 1.0% from one individual to another may not be meaningful.</em></p><p><em></em></p><p><em>Although HbA1c varies among individuals with the same average bG, it is very stable for any given individual. Thus a change of 1.0% in your own HbA1c is definitely meaningful.</em></p><p><em></em></p><p><em>Third and final trick: <strong>most medical professionals have been given incorrect information about the timeframe which HbA1c represents. Even textbooks normally state the 90-120 day average</strong>, as does the American Diabetes Association in its Position Statement on Tests of Glycemia in Diabetes (see reference 1).</em></p><p><em></em></p><p><em><strong>The longer estimate is based on the assumption that the conversion of hemoglobin A to HbA1c is essentially irreversible. This was a reasonable assumption before the reaction rates were actually measured.</strong> See the following section for information about the research which measured the reaction rates and simulated the consequences.</em></p><p><em></em></p><p><em>See the following section for the references mentioned above.</em></p><p><em></em></p><p><em></em></p><p><em></em></p><p><em>Subject: Who determined the HbA1c reaction rates and the consequences?</em></p><p><em></em></p><p><em>In the early 1980s, Henrik Mortensen and colleagues at Glostrup University Hospital, in Denmark, measured the reaction rates in vitro. Their results showed the assumption of irreversibility to be untrue. In fact the reverse reaction (HbA1c to HbA and glucose) proceeds at about 1/8 the rate of the forward reaction, which is very far from irreversible. Mortensen et alia also built a biokinetic model based on the measurements, and validated the model by comparing its predictions to actual patients. See references 3-5.</em></p><p><em></em></p><p><em>Among other things, Mortensen's work shows that after a change in average bG level, the HbA1c level restabilizes after about 4 weeks. This has several consequences. Clinically, the most important are these:</em></p><p><em></em></p><p><em>First, the HbA1c is an exponentially weighted average of blood glucose levels from the preceding 4 weeks, with the most recent 2 weeks being by far the most important.</em></p><p><em></em></p><p><em>Second, measuring HbA1c less often than monthly results in unmonitored gaps between measurements. To use HbA1c as a continuous monitoring tool, you need to check it at least once a month.</em></p><p><em></em></p><p><em>Third, it is worthwhile checking the HbA1c of newly diagnosed patients as often as once a week to determine the effectiveness of the newly imposed treatment.</em></p><p><em></em></p><p><em>Reference 1: American Diabetes Association, Tests of Glycemia in Diabetes, Diabetes Care 23:S80-S82, January 2000 Supplement 1. This specific issue is no longer available online, but the most recent version is available at <a href="http://diabetes.org/cpr/" target="_blank">http://diabetes.org/cpr/</a>.</em></p><p><em></em></p><p><em>Reference 2: Kilpatrick ES, Maylor PW, Keevil BG: Biological Variation of Glycated Hemoglobin. Diabetes Care 21:261-264, February 1998. Abstract available on the web at <a href="http://care.diabetesjournals.org/cgi...tract/21/2/261" target="_blank">http://care.diabetesjournals.org/cgi...tract/21/2/261</a>.</em></p><p><em></em></p><p><em>Reference 3: Mortensen HB, Christophersen C: Glucosylation of human haemoglobin a in red blood cells studied in vitro. Kinetics of the formation and dissociation of haemoglobin A1c. Clinica Chimica Acta 134:317-326, 15 November 1983.</em></p><p><em></em></p><p><em>Reference 4: Mortensen HB, Volund A, Christophersen C: Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model. Clinica Chimica Acta 136:75-81, 16 January 1984.</em></p><p><em></em></p><p><em>Reference 5: Mortensen HB, Volund A: Application of a biokinetic model for prediction and assessment of glycated haemoglobins in diabetic patients. Scandinavian Journal of Clinical and Laboratory Investigation 48:595-602, October 1988.</em></p></blockquote><p></p>
[QUOTE="reidpj, post: 233636, member: 36922"] Hi All "The longer estimate [3-4 months] is based on the assumption that the conversion of hemoglobin A to HbA1c is essentially irreversible. This was a reasonable assumption before the reaction rates were actually measured". See below: [i]Charly Coughran [email=ccoughran@DELETE-TO-RESPOND-UCSD.EDU]ccoughran@DELETE-TO-RESPOND-UCSD.EDU[/email] Subject: What's HbA1c and what's it mean? Hb = hemoglobin, the compound in the red blood cells that transports oxygen. Hemoglobin occurs in several variants; the one which composes about 90% of the total is known as hemoglobin A. A1c is a specific subtype of hemoglobin A. The 1 is actually a subscript to the A, and the c is a subscript to the 1. "Hemoglobin" is also spelled "haemoglobin", depending on your geographic allegiance. [b]Glucose binds slowly to hemoglobin A, forming the A1c subtype. The reverse reaction, or decomposition, proceeds relatively slowly, so any buildup persists for roughly 4 weeks. Because of the reverse reaction, the actual HbA1c level is strongly weighted toward the present. Some of the HbA1c is also removed when erythrocytes (red blood cells) are recycled after their normal lifetime of about 90-120 days. These factors combine so that the HbA1c level represents the average bGlevel of approximately the past 4 weeks, strongly weighted toward the most recent 2 weeks. It is almost entirely insensitive to bG levels more than 4 weeks previous.[/b] In non-diabetic persons, the formation, decomposition and destruction of HbA1c reach a steady state with about 3.0% to 6.5% of the hemoglobin being the A1c subtype. Most diabetic individuals have a higher average bG level than non-diabetics, resulting in a higher HbA1c level. The actual HbA1c level can be used as an indicator of the average recent bG level. This in turn indicates the possible level of glycation damage to tissues, and thus of diabetic complications, if continued for years. Interpreting HbA1c values can be tricky for several reasons. See the following section for more details. Subject: Why is interpreting HbA1c values tricky? Interpreting HbA1c values is tricky for several reasons: differing lab measurements, variation among individuals, and misapprehension of the relevant timeframe. First trick: several different lab measurements have been introduced since 1980, measuring slightly different subtypes with different limits for normal values and thus different interpretive scales. A National Glycohemoglobin Standardization Program began in 1996, sponsored by the American Diabetes Association and others. See reference 1. This program certifies HbA1c assays which conform to the method used in the DCCT. However, as of 1998 other versions are still in use in many places, both in the US and elsewhere. When you get a lab result, be sure to look at what the lab considers to be the normal range. Most discussion of HbA1c values in m.h.d appears to be based on the DCCT, where the normal range is approximately 3.0-6.1%. Caveat lector. (See part 5, Research, of this FAQ for more information on the DCCT, the Diabetes Control and Complications Trial.) Second trick: HbA1c levels appear to vary by up to 1.0% among individuals with the same average bG. See reference 2. This is very recent research and its implications are not yet clear. The actual reaction rates governing the formation of HbA1c may vary among individuals. Some of the variation may be due to differences in erythrocyte (red blood cell) survival times -- the rough 90-120 day range noted earlier -- although other work limits this to a small part of the total variation (see reference 5). Variations in the HbA1c formation rate may or may not correlate with the rate of damage to other tissues. While we await further research, we can only say that differences of 1.0% from one individual to another may not be meaningful. Although HbA1c varies among individuals with the same average bG, it is very stable for any given individual. Thus a change of 1.0% in your own HbA1c is definitely meaningful. Third and final trick: [b]most medical professionals have been given incorrect information about the timeframe which HbA1c represents. Even textbooks normally state the 90-120 day average[/b], as does the American Diabetes Association in its Position Statement on Tests of Glycemia in Diabetes (see reference 1). [b]The longer estimate is based on the assumption that the conversion of hemoglobin A to HbA1c is essentially irreversible. This was a reasonable assumption before the reaction rates were actually measured.[/b] See the following section for information about the research which measured the reaction rates and simulated the consequences. See the following section for the references mentioned above. Subject: Who determined the HbA1c reaction rates and the consequences? In the early 1980s, Henrik Mortensen and colleagues at Glostrup University Hospital, in Denmark, measured the reaction rates in vitro. Their results showed the assumption of irreversibility to be untrue. In fact the reverse reaction (HbA1c to HbA and glucose) proceeds at about 1/8 the rate of the forward reaction, which is very far from irreversible. Mortensen et alia also built a biokinetic model based on the measurements, and validated the model by comparing its predictions to actual patients. See references 3-5. Among other things, Mortensen's work shows that after a change in average bG level, the HbA1c level restabilizes after about 4 weeks. This has several consequences. Clinically, the most important are these: First, the HbA1c is an exponentially weighted average of blood glucose levels from the preceding 4 weeks, with the most recent 2 weeks being by far the most important. Second, measuring HbA1c less often than monthly results in unmonitored gaps between measurements. To use HbA1c as a continuous monitoring tool, you need to check it at least once a month. Third, it is worthwhile checking the HbA1c of newly diagnosed patients as often as once a week to determine the effectiveness of the newly imposed treatment. Reference 1: American Diabetes Association, Tests of Glycemia in Diabetes, Diabetes Care 23:S80-S82, January 2000 Supplement 1. This specific issue is no longer available online, but the most recent version is available at [url=http://diabetes.org/cpr/]http://diabetes.org/cpr/[/url]. Reference 2: Kilpatrick ES, Maylor PW, Keevil BG: Biological Variation of Glycated Hemoglobin. Diabetes Care 21:261-264, February 1998. Abstract available on the web at [url=http://care.diabetesjournals.org/cgi...tract/21/2/261]http://care.diabetesjournals.org/cgi...tract/21/2/261[/url]. Reference 3: Mortensen HB, Christophersen C: Glucosylation of human haemoglobin a in red blood cells studied in vitro. Kinetics of the formation and dissociation of haemoglobin A1c. Clinica Chimica Acta 134:317-326, 15 November 1983. Reference 4: Mortensen HB, Volund A, Christophersen C: Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model. Clinica Chimica Acta 136:75-81, 16 January 1984. Reference 5: Mortensen HB, Volund A: Application of a biokinetic model for prediction and assessment of glycated haemoglobins in diabetic patients. Scandinavian Journal of Clinical and Laboratory Investigation 48:595-602, October 1988.[/i] [/QUOTE]
Verification
Post Reply
Home
Forums
Diabetes Discussion
Diabetes Discussions
HbA1c represents a 4 week average?
Top
Bottom
Find support, ask questions and share your experiences. Ad free.
Join the community »
This site uses cookies. By continuing to use this site, you are agreeing to our use of cookies.
Accept
Learn More.…