Hemoglobin A1C

Order Code

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2708

Preferred Specimen

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4 mL of EDTA whole blood. Store refrigerated.

Note: The assay may be impacted by hemoglobinopathies (such as sickle cell anemia, S-C disease, etc.) or may show artificially low results in conditions involving reduced red blood cell survival (e.g., hemolytic anemias, blood loss, etc.). In such cases, alternative testing or consultation with the laboratory is recommended.

ContainerType

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EDTA (lavender top) tube

Minimum Volume

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Adult: 3 mL whole blood.
Pediatric: 0.1 mL whole blood (does not allow for
repeat or additional testing).

Transport Temperature

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Refrigerated

Expected Turnaround Time

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1 day

Specimen Stability

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14 days room temperature; 7 days refrigerated; 6 months frozen

Methodology

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turbidimetric inhibition immunoassay (tinia). Roche/hitachi a1cdx gen.3.

Rejection Criteria

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• Allow only one freeze/thaw cycle

Overview

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Glycated hemoglobin, also referred to as glycohemoglobins, hemoglobin A1C (HbA1C), or simply A1C, is hemoglobin that binds with glucose, and its concentration in the blood reflects the average blood glucose levels over the past two to three months. Since red blood cells are permeable to glucose, once hemoglobin becomes glycated, it remains stable for the life of the red blood cell. HbA1C represents a specific fraction of hemoglobin A, the most common type of hemoglobin found in the body, accounting for about 95% to 96% of it. The percentage of glycated hemoglobin, often referred to as HbA1C or A1C in clinical results, offers a snapshot of the average blood glucose over the lifespan of the red blood cell, approximately 120 days. However, HbA1C reflects a weighted average of blood glucose, with about half of the value coming from glucose concentrations in the 30 days leading up to the test. Importantly, HbA1C remains relatively stable and is not significantly affected by short-term fluctuations in glucose levels. Measuring HbA1C is crucial, as research has shown that maintaining tight glycemic control can reduce the risk of long-term complications associated with diabetes, such as nephropathy, neuropathy, and retinopathy.

Since 2010, the American Diabetes Association (ADA) has used an HbA1C level of 6.5% or greater as a diagnostic criterion for diabetes mellitus. The test is used to screen for prediabetes and diabetes, diagnose these conditions in adults, and monitor treatment, with type 1 diabetes patients typically tested every 3 months, while type 2 patients may be tested every 6 months if their treatment goals are stable. Racial and ethnic differences in HbA1C levels have been observed, with studies showing that Black American, Hispanic American, and Asian American populations tend to have higher HbA1C values compared to White Americans, even when plasma glucose concentrations are similar. These differences are thought to be due to genetic factors. The ADA has outlined specific diagnostic criteria for diabetes, including an HbA1C of ≥6.5%, a fasting blood glucose of ≥126 mg/dL (7.0 mmol/L), a two-hour plasma glucose of ≥200 mg/dL (11.1 mmol/L) after a 75-g oral glucose tolerance test, or a random blood glucose level of ≥200 mg/dL (11.1 mmol/L) with typical symptoms of hyperglycemia.

A common treatment goal is to maintain an HbA1C level of less than 7% to minimize the risk of complications, although higher targets may be suitable for certain populations, such as the elderly or those with higher risk of hypoglycemia. However, several factors can lead to inaccurate HbA1C measurements. These include conditions that cause rapid red cell turnover, such as acute or chronic blood loss, hemolytic anemia, or sickle cell disease, which may falsely lower HbA1C readings. Conversely, low red cell turnover, as seen in conditions like high hematocrit, iron deficiency anemia, lead poisoning, or hypothyroidism, may result in falsely elevated HbA1C values. Hemoglobin variants, such as HbF, can also affect the accuracy of HbA1C testing, causing either overestimation or underestimation depending on the method used.

Clinical Significance

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Screening: Used to identify prediabetes and diabetes in adults

Diagnosis: Helps diagnose prediabetes and type 2 diabetes in both adults and children

Monitoring:

• For type 1 diabetes, typically measured every 3 months
• For type 2 diabetes, every 6 months if treatment goals are being met and glycemic control is stable; otherwise, it should be checked every 3–4 months to track therapy adjustments

Additional Information

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The term “hemoglobin A1C” derives from the order of elution of glycated hemoglobins when separated via chromatographic techniques (e.g., HbAC, HbA1A, HbA1B, HbA1C, etc.). To standardize clinical testing, most assays are calibrated to measure HbA1C, or are designed to yield results equivalent to that measurement.

Several studies have found racial and ethnic variations in HbA1C levels. For instance, Black American, Hispanic American, and Asian American populations often exhibit higher HbA1C values compared to White Americans with similar plasma glucose levels. These differences, typically around 0.3 to 0.4 percentage points, are believed to be genetically based and independent of average glucose concentration (Menke, 2014; Selvin, 2020).

ADA Diagnostic Criteria for Diabetes:

• HbA1C ≥6.5%
• Fasting blood glucose ≥126 mg/dL (7.0 mmol/L), with fasting defined as no caloric intake for at least 8 hours
• Two-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) following a 75-g oral glucose tolerance test
• Random blood glucose ≥200 mg/dL (11.1 mmol/L), when accompanied by classic symptoms of hyperglycemia (e.g., polyuria, polydipsia, polyphagia, blurred vision) (ADA, 2021)

A common treatment target to minimize diabetes-related complications is an HbA1C of <7%. However, higher targets may be considered for specific groups, such as the elderly or individuals with limited access to healthcare, where the risk of hypoglycemia may outweigh the benefits of tighter glucose control.

Interpretative Information

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HbA1C in Adults >19 Years of Age

The table was created using the formula for calculating the estimated average glucose (eAG): (28.7 x A1C) – 46.7 = eAG mg/dL

https://www.diabetes.org/diabetes/a1c-test-meaning/a1c-and-eag

Limitations

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Several conditions can lead to inaccurate HbA1C measurements:

• Misleading decrease in HbA1C (due to rapid red cell turnover, which results in a higher proportion of younger red blood cells and falsely low A1C values):
  • Acute or chronic blood loss
  • Hemolytic anemias
  • Conditions shortening red cell lifespan (e.g., sickle cell disease, HbCC, HbSC)
  • Presence of hemoglobin F (HgF >10% of total Hb, typically seen in children under 2 years but may be present in some adults)
  • Nutritional deficiencies (e.g., folate, vitamin B12, vitamin B6)
  • Advanced renal disease, especially with hemodialysis and erythropoietin treatment
  • Liver disease
  • Splenomegaly
• Misleading increase in HbA1C (due to low red cell turnover, resulting in a higher proportion of older red cells):
  • High hematocrit
  • Iron deficiency or folate/B12 anemia
  • Lead poisoning
  • Overt hypothyroidism
  • Late-stage pregnancy
  • Corticosteroid use (can cause transient hyperglycemia)
  • Recent blood transfusions (as blood preservative solutions may contain high glucose concentrations)
• Mixed effects: Hemoglobin variants can also skew HbA1C readings, with hemoglobin F overestimating A1C levels and hemoglobins S and C potentially underestimating them, depending on the testing method (NGSP, 2020).

References

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Diagnostic Role

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Hemoglobin A1C (HbA1C) is a blood test used to diagnose prediabetes and diabetes as well as an important test to monitor and manage diabetes over time. The goal of diabetic management is to keep blood glucose levels as close to normal as possible; the higher the HbA1C level, the higher the risk of developing diabetes or diabetes complications (DCCT 1993). To assist with control of blood glucose levels, the American Diabetes Association (ADA) has recommended HbA1C testing twice a year for patients with stable glucose control, and quarterly for patients with poor glucose control (ADA 2021).

It is important to note that HbA1C does not reflect daily glucose variations; whole blood glucose fingerstick measurements remain the key test for real-time information. As HbA1C represents the average of glucose control over a two to three month period, both wide glucose ranges and narrow glucose ranges may have same average blood glucose, and consequently similar HbA1C results (AACC 2020). HbA1C and glucose fingersticks provide complementary information to optimize glucose control.

An important clinical limitation of HbA1C relates to the average red blood cell lifespan. In those medical conditions where RBC turnover is increased or decreased, the HbA1C is less reliable than blood glucose measurements. Examples of such conditions include sickle cell disease, various anemias, pregnancy (second and third trimesters), recent blood loss or transfusion, erythropoietin therapy, or hemodialysis.

Alias

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• glycohemoglobin
• hba1c
• hgb a1c

Test Setup Days

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Monday through Saturday PM shift

CPT

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83036 Limited Coverage Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Required
If Diagnosis Is Not Covered.
Frequency Limit Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Always
Required For Frequency.
LOINC: 4548-4

Reference Range

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4.2-5.6%