Originally discovered in the 1960s, hemoglobin A1c (HbA1c) became a reliable indicator of long-term glycemic control by capturing the average blood glucose levels over several months. Since its initial recognition, HbA1c has evolved into a cornerstone in diabetes care, offering a comprehensive perspective on a patient's glucose regulation. Over the decades, the HbA1c test has undergone refinements, standardizations, and continuous validation, becoming an indispensable tool for healthcare practitioners in tailoring personalized treatment plans and guiding patients toward optimal health outcomes. This historical trajectory underscores the importance of HbA1c testing in shaping the landscape of diabetes management. It highlights its ongoing role in promoting proactive and individualized care for those affected by this prevalent metabolic disorder. (12)

[signup]

Understanding HbA1c and Its Clinical Relevance

Hemoglobin A1c, commonly called HbA1c, is a crucial marker in diabetes management, serving as a reliable indicator of long-term blood glucose control. This glycosylated form of hemoglobin, a protein found in red blood cells (RBCs) responsible for transporting oxygen, is formed when hemoglobin molecules bond with glucose (sugar) in the bloodstream. As blood glucose levels fluctuate, a portion of the circulating glucose becomes bound to hemoglobin in a non-enzymatic reaction. This reaction, called glycosylation, occurs continuously over the lifespan of RBCs, which typically have a lifespan of about 120 days. Therefore, HbA1c reflects the average blood glucose concentration over the preceding 2 to 3 months. The percentage value obtained from the HbA1c test corresponds to the proportion of glycated hemoglobin relative to total hemoglobin. For instance, an HbA1c level of 6% indicates that 6% of the total hemoglobin in the blood has bonded with glucose. Clinically, HbA1c is used to screen for prediabetes and type 2 diabetes and to assess the efficacy of diabetes management strategies. Intensive control of diabetes, reflected in lower HbA1c levels, reduces the onset and slows the progression of diabetes-related complications.

HbA1c Test: Procedure and Accuracy

HbA1c tests can be performed in two ways: a blood draw, such as the whole blood Hemoglobin A1c test by Access Med Labs, or a finger prick, such as the blood spot HbA1c test by Ayumetrix. Patients are not required to fast for either version of the test. The venipuncture (blood draw) method of sample collection generally results in more accurate HbA1c results than the finger prick test. 

Since 2010, the American Diabetes Association (ADA) has recommended using HbA1c as a diagnostic tool for prediabetes and diabetes. Labs now use an NGSP-certified method for analyzing blood samples to determine HbA1c levels, making results more precise. The NGSP, or National Glycohemoglobin Standardization Program, is an organization that works to standardize HbA1c test results and make them more comparable across different laboratories and methods. The NGSP was established to address variations in HbA1c test results that could arise from different laboratory measurement methods and technologies. The NGSP expresses HbA1c results in terms of the Diabetes Control and Complications Trial (DCCT) standard, which is based on the relationship between HbA1c levels and the risk of diabetes-related complications.

Interpreting HbA1c Test Results

For diagnosing purposes, the following ranges are used to interpret HbA1c results:

• Normal: less than 5.7%
• Prediabetes: 5.7% to 6.4%
• Diabetes: 6.5% or higher

Factors that affect the lifespan and health of RBCs can influence the accuracy of the HbA1c test, leading results to be falsely low or high. Typical problems that interfere with results are attributed to hemoglobin variants, anemia, chronic kidney disease, pregnancy, elevated bilirubin levels, elevated triglycerides, certain medications (e.g., immunosuppressants and antiretrovirals), alcohol use disorder, and blood transfusions. Errors in collecting, transporting, or processing the test can also lead to inaccurate test results. Therefore, interpreting HbA1c results in the context of a patient's medical history is important to avoid false diagnoses. Additionally, any test used to diagnose diabetes requires confirmation with a second measurement. (1, 18) 

HbA1c and Diabetes Management

After a patient is diagnosed with diabetes, healthcare professionals will use the HbA1c test to set treatment goals, modify therapy, and monitor disease management. Per ADA guidelines, HbA1c should be measured twice yearly in stable patients and at least four times annually in patients with significant blood sugar fluctuations or who have recently changed their diabetic treatment. The ADA has set an HbA1c treatment goal of less than 7% for non-pregnant diabetic adults. This target reflects a balance between achieving optimal glycemic control to reduce the risk of diabetes-related complications and avoiding the potential for hypoglycemia. Maintaining HbA1c levels below 7% has been associated with a lower risk of long-term complications, including cardiovascular disease, kidney disease, and neuropathy. The DCCT demonstrated that intensive blood glucose control, resulting in lower HbA1c levels, significantly reduced the risk of these complications in individuals with type 1 diabetes.

However, it's crucial to recognize that individualized care is paramount in diabetes management. The recommended HbA1c goal may be adjusted based on factors such as age, comorbidities, and the risk of hypoglycemia. For example, older adults with multiple coexisting chronic conditions or mild-to-moderate cognitive impairment may follow a less stringent HbA1c goal of less than 8% to avoid the potential risks associated with overly aggressive glycemic control.

HbA1c in Prediabetes and Risk Assessment

More than one in three American adults have prediabetes, a health condition characterized by higher-than-normal blood sugar that is not yet high enough to be classified as type 2 diabetes. Recognizing prediabetes before it advances to type 2 diabetes allows for proactive and individualized interventions addressing root causes to reverse dysglycemia and prevent the burden of chronic diseases associated with diabetes. Without intervention, most people with prediabetes will develop type 2 diabetes within ten years. However, lifestyle modifications, including losing 7% of body weight and increasing moderate physical activity to 150 minutes per week, reduce the risk of diabetes by as much as 58%. (20)

Having prediabetes is a risk factor for developing type 2 diabetes. The higher within the prediabetic HbA1c range of 5.7-6.4%, the greater the risk of developing diabetes (18). HbA1c can, therefore, be used to help predict an individual's risk for type 2 diabetes and monitor their response to therapeutic interventions in preventing disease progression.   

Patient Education and Empowerment

Patient education is crucial in diabetes management, serving as a cornerstone for empowering individuals to participate in their care actively. Doctors should effectively communicate HbA1c results and their implications to patients. Clear and accessible explanations regarding the significance of HbA1c help patients understand the long-term control of their diabetes. 

An important piece of information that must be relayed to patients is that HbA1c does not replace regular blood sugar testing. HbA1c levels don't capture daily blood sugar fluctuations. Two individuals may share the same HbA1c, yet one might maintain stable blood sugar levels while the other experiences frequent highs and lows. Oscillations in blood glucose (called glycemic variability) are linked to increased risk of macro- and microvascular complications, hypoglycemia, and mortality. Therefore, a critical aspect of diabetic care and management is educating patients on how and when to measure blood sugar levels during the day. (3) 

Continuous glucose monitoring (CGM) is an innovative technology in diabetes management that provides real-time information on blood glucose levels through a sensor placed under the skin. This tool offers a detailed view of glucose patterns, allowing users to understand how their blood sugar responds to various factors, such as diet, hydration, sleep patterns, and stress. CGM enables personalized discussions between healthcare providers and patients based on real-world data, leading to targeted interventions and improved treatment plans. The technology enhances awareness of hypoglycemia and hyperglycemia, with alerts prompting timely actions. CGM empowers individuals to actively engage in self-management by visualizing their glucose data, ultimately contributing to better adherence and overall outcomes in diabetes care.

Future Directions and Emerging Research

Emerging research in HbA1c testing focuses on refining its applications and leveraging technological advancements to enhance clinical utility and accuracy. One notable area of exploration is advancing HbA1c point-of-care testing (POCT). POCT refers to medical diagnostic testing conducted near the patient, typically at or near the location where healthcare services are provided, rather than sending samples to a centralized laboratory. The primary goal of POCT is to generate rapid results that can facilitate immediate clinical decision-making and patient management. HbA1c POCT is revolutionizing diabetes care by providing quick and accurate results at the point of patient contact, enabling prompt discussions on treatment plans and lifestyle modifications. This approach enhances efficiency and patient engagement and facilitates real-time adjustments to optimize diabetes management. (6) 

Advancements in technology, particularly in CGM and flash glucose monitoring (FGM) systems, are reshaping the landscape of glycemic monitoring. Integrating real-time glucose data from CGM with HbA1c results offers a more comprehensive understanding of a patient's glycemic profile. This integration allows personalized treatment adjustments based on short-term and long-term glucose trends. (7) 

[signup]

How to Interpret An HbA1c Test: Key Takeaways

The HbA1c test stands as a critical and indispensable tool in managing the health of individuals, especially those with or at risk of diabetes. Its ability to reflect average blood glucose levels over several months offers valuable insights into long-term glycemic control. Healthcare practitioners are encouraged to utilize HbA1c in clinical practice as a powerful tool for informed decision-making and patient education. By incorporating this comprehensive measure into routine care, practitioners can enhance their ability to tailor interventions, educate patients on personalized management strategies, and ultimately contribute to more effective and proactive diabetes care. Utilizing HbA1c in clinical practice is not just a diagnostic measure but a dynamic approach to optimizing patient outcomes and fostering a collaborative and informed healthcare model.