Definition of hba1c. HbA1c Test: Understanding Glycated Hemoglobin and Diabetes Management

08.07.202303.07.2023 by alexxlab

What is the HbA1c test. How does it measure blood glucose control. Why is HbA1c important for diabetes diagnosis and management. What factors can affect HbA1c results. How often should HbA1c be tested.

Содержание

What is Hemoglobin A1c (HbA1c) and Its Significance in Diabetes Care?

Hemoglobin A1c, also known as HbA1c or A1c, is a crucial biomarker in diabetes management. This test provides valuable insights into a person’s average blood glucose levels over the past 90 days. But how does it work?

HbA1c is formed when glucose in the bloodstream attaches to hemoglobin, the oxygen-carrying protein in red blood cells. As blood sugar levels rise, more glucose binds to hemoglobin, resulting in higher HbA1c percentages. This glycation process makes HbA1c an excellent indicator of long-term glucose control.

Key Points About HbA1c:

Reflects average blood sugar over approximately 3 months
Expressed as a percentage
Used for both diagnosis and monitoring of diabetes
Provides a more stable measure than daily blood glucose readings

Can HbA1c replace daily blood glucose monitoring? While HbA1c offers a comprehensive overview, it doesn’t capture day-to-day fluctuations or immediate glucose levels. Therefore, it complements rather than replaces regular blood glucose testing for optimal diabetes management.

The HbA1c Test: Procedure, Interpretation, and Diagnostic Criteria

Understanding the HbA1c test procedure and interpretation is essential for both healthcare providers and patients. How is this test performed, and what do the results mean?

HbA1c Test Procedure:

Blood sample collection (venous or capillary)
Laboratory analysis or point-of-care testing
Results typically available within a few days or minutes (for rapid tests)

The American Diabetes Association (ADA) has established clear guidelines for interpreting HbA1c results:

Below 5.7%: Normal (non-diabetic) range
5.7% to 6.4%: Prediabetes
6.5% or higher: Diabetes

Is a single HbA1c test sufficient for diabetes diagnosis? While a result of 6.5% or higher suggests diabetes, the ADA recommends confirming the diagnosis with a second test, especially if the initial test was a point-of-care capillary blood test.

The Impact of HbA1c on Diabetes Complications and Long-term Health

The relationship between HbA1c levels and diabetes complications has been extensively studied. What have researchers discovered about this crucial connection?

The Diabetes Control and Complications Trial (DCCT) was a groundbreaking study that shed light on the importance of glycemic control in preventing diabetes-related complications. The study found that maintaining lower HbA1c levels significantly reduced the risk of microvascular complications such as retinopathy, nephropathy, and neuropathy.

Key Findings from DCCT and Follow-up Studies:

35-76% decrease in microvascular complications with HbA1c levels around 7% or lower
Reduced cardiovascular risk and mortality in the long term with better glycemic control
Established HbA1c as a dominant predictor of diabetic retinopathy progression

How does improved glycemic control translate to better health outcomes? Lower HbA1c levels indicate less glucose circulating in the bloodstream over time. This reduction in glucose exposure helps protect blood vessels, nerves, and organs from damage, ultimately leading to fewer complications and improved quality of life for people with diabetes.

Factors Influencing HbA1c Results: Understanding Potential Inaccuracies

While HbA1c is a valuable tool in diabetes management, several factors can affect its accuracy. What conditions or circumstances might lead to misleading HbA1c results?

Conditions That May Cause Falsely Low HbA1c:

Hemolytic anemia
Chronic kidney failure
Liver cirrhosis
Sickle cell anemia
Recent blood transfusions
Pregnancy
High altitude exposure

Factors That May Cause Falsely High HbA1c:

Iron deficiency anemia
Vitamin B12 deficiency
Certain medications

How should healthcare providers interpret HbA1c results in patients with these conditions? It’s crucial to consider the patient’s overall clinical picture and use additional glucose measurements to confirm diabetes status or assess glycemic control. In some cases, alternative methods like fructosamine or glycated albumin tests may be more appropriate.

HbA1c Testing Frequency and Diabetes Management Goals

Regular HbA1c testing is an integral part of diabetes management. How often should this test be performed, and what are the target levels for optimal health?

The American Diabetes Association recommends the following testing schedule:

Twice a year for patients with stable and well-controlled diabetes
Every 3 months for patients with recent medication changes or suboptimal control

Target HbA1c levels may vary depending on individual factors, but general guidelines include:

Below 7% for most adults with diabetes
Below 6.5% for some patients, if achievable without significant hypoglycemia
Below 8% for patients with a history of severe hypoglycemia or limited life expectancy

Should HbA1c goals be the same for everyone with diabetes? It’s important to note that these targets are general guidelines. Healthcare providers should work with patients to establish individualized goals based on factors such as age, comorbidities, diabetes duration, and personal preferences.

Advances in HbA1c Testing: Point-of-Care Devices and Standardization Efforts

The field of HbA1c testing has seen significant advancements in recent years. What innovations are improving the accessibility and reliability of these tests?

Point-of-Care (POC) HbA1c Testing:

Rapid results (usually within minutes)
Convenient for immediate clinical decision-making
Potential for improved patient engagement and adherence

However, it’s important to note that POC tests may have slightly lower accuracy compared to laboratory-based methods. For this reason, any diabetes diagnosis based on a POC HbA1c test should be confirmed with a laboratory test.

To ensure consistency and reliability across different testing methods and laboratories, the National Glycohemoglobin Standardization Program (NGSP) was established. This program works to standardize HbA1c test results to those used in the DCCT, allowing for more accurate diagnosis and management of diabetes worldwide.

How has standardization improved diabetes care? By ensuring that HbA1c results are consistent and comparable across different healthcare settings, standardization efforts have enhanced the reliability of diabetes diagnosis and the ability to track glycemic control over time, regardless of where the test is performed.

HbA1c in Special Populations: Considerations for Accurate Interpretation

While HbA1c is a valuable tool for most individuals, certain populations require special consideration when interpreting results. How should HbA1c be approached in these groups?

Pregnancy:

HbA1c levels naturally decrease during pregnancy due to increased red blood cell turnover. This can lead to falsely low readings. For this reason, healthcare providers often rely more heavily on frequent blood glucose monitoring and oral glucose tolerance tests for managing gestational diabetes.

Elderly Patients:

Older adults may have higher HbA1c targets to reduce the risk of hypoglycemia. The American Diabetes Association suggests less stringent goals (such as below 8%) for elderly patients with multiple comorbidities or limited life expectancy.

Children and Adolescents:

Pediatric diabetes management often aims for tighter glycemic control when possible. The International Society for Pediatric and Adolescent Diabetes recommends an HbA1c target of less than 7% for most children and adolescents with type 1 diabetes.

Ethnic Variations:

Research has shown that HbA1c levels can vary among different ethnic groups, even at similar blood glucose levels. For example, people of African, Mediterranean, or Southeast Asian descent may have slightly higher HbA1c levels than those of European descent with the same degree of glycemia.

How should these variations be addressed in clinical practice? Healthcare providers should be aware of these potential differences and consider them when interpreting HbA1c results. In some cases, it may be necessary to rely more heavily on other measures of glycemic control, such as fasting plasma glucose or continuous glucose monitoring data.

Beyond HbA1c: Complementary Measures of Glycemic Control

While HbA1c remains a cornerstone of diabetes management, other measures can provide additional insights into glycemic control. What complementary tools are available to healthcare providers and patients?

Continuous Glucose Monitoring (CGM):

CGM devices provide real-time glucose readings throughout the day and night, offering a more detailed picture of glucose fluctuations. This technology can reveal patterns that may not be apparent from HbA1c alone, such as frequent hypoglycemia or post-meal spikes.

Time in Range (TIR):

TIR is a metric derived from CGM data that indicates the percentage of time a person’s glucose levels are within a target range (typically 70-180 mg/dL). This measure provides information about glycemic variability, which HbA1c does not capture.

Fructosamine and Glycated Albumin:

These tests reflect average glucose levels over a shorter period (2-3 weeks) compared to HbA1c. They can be useful in situations where HbA1c may be unreliable, such as in patients with certain hemoglobin variants or rapid red blood cell turnover.

1,5-Anhydroglucitol (1,5-AG):

This test reflects glucose control over the past 1-2 weeks and is particularly sensitive to post-meal glucose excursions. It can be a helpful adjunct to HbA1c in assessing overall glycemic control.

How do these complementary measures enhance diabetes management? By providing a more comprehensive view of glucose patterns and variability, these tools allow for more personalized and precise diabetes management. They can help identify specific areas for improvement, such as nighttime hypoglycemia or post-meal hyperglycemia, that may not be evident from HbA1c alone.

In conclusion, while HbA1c remains an essential tool in diabetes care, understanding its limitations and complementing it with other measures can lead to more effective and personalized diabetes management strategies. As technology and research continue to advance, the landscape of glycemic monitoring is likely to evolve, offering even more sophisticated ways to assess and improve glucose control in people with diabetes.

Hemoglobin A1C – StatPearls – NCBI Bookshelf

Introduction

The hemoglobin A1c (glycated hemoglobin, glycosylated hemoglobin, HbA1c, or A1c) test is used to evaluate a person’s level of glucose control. The test shows an average of the blood sugar level over the past 90 days and represents a percentage. The test can also be used to diagnose diabetes.[1]

Hemoglobin is a protein only found in red blood cells. In fact, hemoglobin is what gives blood its bright red coloring. Since red blood cells live about an average of three months, the A1c test will reflect those red blood cells that are present in the bloodstream at the time of the test; this is why the A1c serves as an average of blood sugar control.

The main job of hemoglobin is to carry oxygen from the lungs to all the cells of the body. Hemoglobin becomes glycated or coated with glucose from the bloodstream. The amount of glucose that is present in the blood will attach to the hemoglobin protein, and increased glucose levels will reflect on the surface of the hemoglobin protein, thereby rendering a higher A1c level. [2]

Etiology and Epidemiology

The Diabetes Control and Complications Trial (DCCT)[3] was a landmark trial that provided a wealth of data on A1c and its correlation to blood glucose levels, as well as establishing specific treat to target A1c goals. From the completion of the trial, the National Glycohemoglobin Standardization Program (NGSP) was formed to define a standardized assay that was usable across laboratories.

The DCCT trial reported that a higher mean A1c level was the dominant predictor of diabetic retinopathy progression. Tighter control shown by levels of HbA1c in the 7% range or lower, were correlated with 35-76% decrease in microvascular complications, like retinopathy, nephropathy and neuropathy, in patients with type 1 diabetes. In addition to the determination of A1c levels predicting progression of microvascular complications, the extension of DCCT into EDIC study showed benefit in the cardiovascular risk and mortality in the longterm for those patients with lower levels of HbA1c. [4][5][6]

Pathophysiology

People with diabetes need to have their A1c checked regularly to determine if their average blood glucose levels are within the target range. The American Diabetes Association (ADA) recommends that the HbA1c is checked twice a year in patients that are stable and well controlled, versus every 3 months in patients with changes in their medications, or not well controlled. [7]

Specimen Requirements and Procedure

The HbA1c test can either be done as a point of care (POC), STAT test, or by sending a sample to a laboratory. The POC test uses a STAT analyzer that evaluates the A1c from a capillary fingerstick. The laboratory test uses a teaspoon of blood drawn from a venous sample into a K2 EDTA (lavender top) tube. The sample gets processed as whole blood.

Diagnostic Tests

The venous sample A1c test may be used as a diagnostic tool in clinical practice when determining diabetes risk or onset. Due to the variability of capillary point of care testing, any A1c done by capillary sample should be confirmed with a venous sample before rendering the diagnosis.

For an HbA1c test to classify as normal, or in the non-diabetic range, the value must be below 5.7 %. Anyone with an HbA1c value of 5.7 % to 6.4 % is considered to be prediabetic, while diabetes can be diagnosed with a HbA1c of 6.5% or higher.

Tests should be sent to a laboratory certified by the NGSP to ensure results are standardized.[8][9]

Testing Procedures

The HbA1c test done by a point of care machine in a doctor’s office may be less accurate than one that is drawn from a venous sample and processed in a laboratory. Typically, the results can vary by different laboratories by as much as 0.5%.

The HbA1c test should be performed using an NGSP-approved method.

Interfering Factors

There are several conditions where the HbA1c test can produce inaccurate results. People diagnosed with sickle cell anemia, thalassemia, anemia, kidney failure, liver disease, or patients receiving blood transfusions can experience altered results due to the longevity of the red blood cell. HbA1c measurement in these patients must be interpreted with caution and should be confirmed with plasma glucose samples to diagnose diabetes.[10]

A falsely low HbA1c value can result from several conditions including high altitude, pregnancy, hemorrhage, blood transfusion, erythropoietin administration, iron supplementation[11], hemolytic anemia, chronic kidney failure, liver cirrhosis, alcoholism, sickle cell anemia[12], and spherocytosis. Vitamin C supplementation can either increase or decrease the HbA1c level depending on the method used for its measurement.[15]

On the other end of the spectrum, a falsely high HbA1c can be due to a lack of available iron in the blood. This condition can result from iron deficiency anemia[13], infection-induced anemia, or tumor-induced anemia. Hemoglobinopathies such as thalassemia and B12 deficiency[11][14] can also cause a falsely high HbA1c. Other causes of falsely high HbA1c levels include hypertriglyceridemia, organ transplantation, and hyperglycation in certain ethnic groups. Medications such as immunosuppressants and protease inhibitors can sometimes lead to a falsely high HbA1c.[10][7][15][16]

Results, Reporting, and Critical Findings

Relationship Between A1c and Glucose Level

The HbA1c percentage equates to an average glucose level in the body that the patient experienced over the past 90 days.[17][18][19]

A1c (%) Average Blood Glucose (mg/dL)

6 126

8 183

10 240

12 298

14 355

Clinical Significance

Hemoglobin A1c serves as an indicator of overall glycemic control and a reflection of the average blood sugar over the past three months.[2]

Quality Control and Lab Safety

Laboratories can use several methods to determine HbA1c. High performance liquid chromatography (HPLC) method is one of the most popular methods because it can eliminate labile components that other methods such as immunoassay or affinity chromatography use. [20]

The point of care (POC) machine is widely used as well to determine HbA1c levels. The variety of POC machines on the market can make it difficult to determine the one best suited for one’s practice. Also, there is a shortage of information comparing the different machines. When using POC testing, one should keep in mind that POC values are often below results reported by a laboratory test, with the mean difference being -0.5%.

Enhancing Healthcare Team Outcomes

All clinicians who look after diabetic patients need to know what HbA1c means. In general, HbA1c provides a measure of the average glucose concentration over three months.

Hemoglobin A1c is often used as an outcome measure to determine if an intervention in a population is successful by showing a decrease in HbA1c by a certain percentage. There is a movement within the medical community to move away from using HbA1c as an exclusive standard of care test to measure patient response to treatment. The Estimated Average Glucose (eAG) and the glucose time in range are the newest proposed methods. [21] These methods use data obtained by continuous glucose monitors (CGMs) that record blood glucose 24 hours a day. They can also give providers a more accurate view of the blood sugar average and fluctuations, but these methods are not available to all patients on a wide-spread basis.

As per ADA guidelines, the levels of HA1c should be measured twice a year in stable patients and at least four times in patients who have glucose fluctuations or those who have had a change in their diabetic treatment. Hemoglobin A1c is one of the preferred diabetes diagnostic tests today. The blood draw can occur at any time, and there are no special handling requirements. However, to ensure that the A1c value is correct, clinicians need to be aware of the causes of false-positive and false-negative results.

Since many patients with diabetes have their condition managed in outpatient clinics, the diabetic nurse should be fully aware of HbA1c values and when to refer the patient to an endocrinologist for further workup and treatment. Pharmacists are also required to fully understand and interpret this test, as they will be involved in glycemic management medication agent selection, dosing, and monitoring. Both the nurse and/or pharmacist need to inform the treating physician regarding any changes in hemoglobin A1c and verify patient medication compliance. Hemoglobin A1c is a very valuable tool in the fight against diabetes and other glycemic control disorders, but to be effective, it functions best in an interprofessional healthcare team environment. [Level V]

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References

1.: Gilstrap LG, Chernew ME, Nguyen CA, Alam S, Bai B, McWilliams JM, Landon BE, Landrum MB. Association Between Clinical Practice Group Adherence to Quality Measures and Adverse Outcomes Among Adult Patients With Diabetes. JAMA Netw Open. 2019 Aug 02;2(8):e199139. [PMC free article: PMC6694385] [PubMed: 31411713]
2.: Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights. 2016;11:95-104. [PMC free article: PMC4933534] [PubMed: 27398023]
3.: Diabetes Control and Complications Trial Research Group. Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. [PubMed: 8366922]
4.: Nathan DM., DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care. 2014;37(1):9-16. [PMC free article: PMC3867999] [PubMed: 24356592]
5.: Nathan DM. Realising the long-term promise of insulin therapy: the DCCT/EDIC study. Diabetologia. 2021 May;64(5):1049-1058. [PubMed: 33550441]
6.: Lachin JM, Orchard TJ, Nathan DM., DCCT/EDIC Research Group. Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37(1):39-43. [PMC free article: PMC3868002] [PubMed: 24356596]
7.: American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021 Jan;44(Suppl 1):S73-S84. [PubMed: 33298417]
8.: American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S61-S70. [PubMed: 30559232]
9.: Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Fitterman N, Balzer K, Boyd C, Humphrey LL, Iorio A, Lin J, Maroto M, McLean R, Mustafa R, Tufte J. Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians. Ann Intern Med. 2018 Apr 17;168(8):569-576. [PubMed: 29507945]
10.: Heinemann L, Freckmann G. Quality of HbA1c Measurement in the Practice: The German Perspective. J Diabetes Sci Technol. 2015 May;9(3):687-95. [PMC free article: PMC4604529] [PubMed: 25691655]
11.: Pilla R, Palleti SK, Rayana R, Skss SR, Abdul Razzack A, Kalla S. Glycated Haemoglobin (HbA1c) Variations in Nondiabetics With Nutritional Anemia. Cureus. 2020 Nov 13;12(11):e11479. [PMC free article: PMC7735166] [PubMed: 33329975]
12.: Lacy ME, Wellenius GA, Sumner AE, Correa A, Carnethon MR, Liem RI, Wilson JG, Sacks DB, Jacobs DR, Carson AP, Luo X, Gjelsvik A, Reiner AP, Naik RP, Liu S, Musani SK, Eaton CB, Wu WC. Association of Sickle Cell Trait With Hemoglobin A1c in African Americans. JAMA. 2017 Feb 07;317(5):507-515. [PMC free article: PMC5713881] [PubMed: 28170479]
13.: Guo W, Zhou Q, Jia Y, Xu J. Increased Levels of Glycated Hemoglobin A1c and Iron Deficiency Anemia: A Review. Med Sci Monit. 2019 Nov 07;25:8371-8378. [PMC free article: PMC6857442] [PubMed: 31696865]
14.: Gram-Hansen P, Eriksen J, Mourits-Andersen T, Olesen L. Glycosylated haemoglobin (HbA1c) in iron- and vitamin B12 deficiency. J Intern Med. 1990 Feb;227(2):133-6. [PubMed: 2299304]
15.: Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014 Feb;29(2):388-94. [PMC free article: PMC3912281] [PubMed: 24002631]
16.: Shepard JG, Airee A, Dake AW, McFarland MS, Vora A. Limitations of A1c Interpretation. South Med J. 2015 Dec;108(12):724-9. [PubMed: 26630892]
17.: van ‘t Riet E, Alssema M, Rijkelijkhuizen JM, Kostense PJ, Nijpels G, Dekker JM. Relationship between A1C and glucose levels in the general Dutch population: the new Hoorn study. Diabetes Care. 2010 Jan;33(1):61-6. [PMC free article: PMC2797987] [PubMed: 19808928]
18.: Sayed A, Alyafei F, De Sanctis V, Soliman A, Elgamal M. Translating the HbA1c assay into estimated average glucose values in children and adolescents with type 1 diabetes mellitus. Acta Biomed. 2018 May 23;89(S5):22-26. [PMC free article: PMC6179094] [PubMed: 30049928]
19.: Lai LC. Global standardisation of HbA1c. Malays J Pathol. 2008 Dec;30(2):67-71. [PubMed: 19291914]
20.: Kawano K. Quality control, quality assessment of laboratory tests, HbA1c. Southeast Asian J Trop Med Public Health. 1999;30 Suppl 3:117-21. [PubMed: 10926271]
21.: Saboo B, Kesavadev J, Shankar A, Krishna MB, Sheth S, Patel V, Krishnan G. Time-in-range as a target in type 2 diabetes: An urgent need. Heliyon. 2021 Jan;7(1):e05967. [PMC free article: PMC7814148] [PubMed: 33506132]

: Disclosure: Emily Eyth declares no relevant financial relationships with ineligible companies.
: Disclosure: Roopa Naik declares no relevant financial relationships with ineligible companies.