An estimated 422 million people have diabetes worldwide. In the last few decades, the number of adults with diabetes has more than doubled; however, one in five don't know they have it. Diabetes is responsible for 1.5 million deaths annually. While these statistics are grave, the good news is that the most common type of diabetes is largely preventable and can be well-managed when diagnosed in the early stages. (16, 44)

The hemoglobin A1c test offers a window into blood sugar balance over the last 2-3 months, giving clues into how blood sugar may affect an individual's cardiometabolic health and risk of diabetes. Hemoglobin A1c is a crucial marker in predicting, preventing, diagnosing, and managing diabetes, providing valuable insights into long-term glycemic control and guiding tailored interventions for individuals at various stages of metabolic dysfunction.

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Understanding Diabetes and Its Impact

Diabetes is a complex metabolic disorder characterized by elevated blood glucose levels, impacting 38 million American adults. There are primarily four types of diabetes: type 1, type 2, gestational diabetes, and a lesser-known type 1.5.

Type 1 diabetes results from an autoimmune response wherein the body's immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. This leads to an insufficient production of insulin, a hormone essential for glucose regulation. Typically diagnosed in childhood or adolescence, type 1 diabetes necessitates lifelong insulin therapy for glucose management. Its onset is often abrupt and can present with symptoms such as excessive thirst, frequent urination, and unexplained weight loss.

Type 2 diabetes, the most prevalent form, is characterized by insulin resistance, wherein the body's cells fail to respond effectively to insulin. This leads to an inability to maintain normal blood glucose levels. Lifestyle factors, genetic predisposition, and obesity play significant roles in the development of type 2 diabetes. Management involves lifestyle modifications, oral medications, and, in some cases, insulin therapy.

Gestational diabetes is a temporary form of diabetes that develops during pregnancy. It occurs when the body cannot produce enough insulin to meet the increased demands, leading to elevated blood glucose levels. While usually temporary, gestational diabetes requires careful management to ensure the well-being of both the mother and the developing fetus. Women with gestational diabetes may be at a higher risk of complications during pregnancy and childbirth. Additionally, there is an increased likelihood of developing type 2 diabetes later in life for both the mother and the child.

Type 1.5 diabetes, also known as Latent Autoimmune Diabetes in Adults (LADA), shares characteristics with both type 1 and type 2 diabetes. Like type 1, it involves an autoimmune response leading to beta cell destruction. However, its progression is slower and typically affects adults, resembling the gradual onset of type 2 diabetes. 

The impact of diabetes on health is profound. Chronic elevation of blood glucose levels can contribute to a range of complications affecting the heart, kidneys, eyes, nerves, and digestive tract. Additionally, diabetes is associated with an increased risk of infections and delayed wound healing. Because of these complications, diabetes is the eighth leading cause of death in the United States and the number one cause of kidney failure, lower-limb amputations, and adult blindness (44).

The Significance of HbA1c in Diabetes Management

The prognosis of individuals with high blood sugar depends on how well blood sugar levels are controlled within an optimal range. Untreated hyperglycemia and high variability of fasting blood glucose are correlated with a shortened lifespan, poorer quality of life, and an increased risk of mortality and cardiovascular events (28, 32). This is because elevated blood glucose levels promote oxidative stress, inflammation, and endothelial dysfunction. Over time, persistent high glucose levels damage blood vessels, impairing their structure and function, ultimately fostering the development of atherosclerosis and microvascular complications. (35)

Hemoglobin A1c (HbA1c) reflects the average blood glucose levels over the past two to three months by measuring the percentage of hemoglobin bound to glucose. The HbA1c blood test is a convenient laboratory tool because it does not require fasting by the patient, and results are not dependent on the time of day. The diagnostic criterion of an HbA1c level of 6.5% or higher has been recommended as an alternative to fasting plasma glucose-based criteria for diabetes. Because HbA1c provides a reliable measure of glucose control over time and correlates well with the risk of diabetic complications, it is currently considered a test of choice for monitoring and managing diabetes. Healthcare professionals rely on HbA1c levels to inform their decision-making process when providing guidance on lifestyle adjustments, pharmaceutical interventions, and nutraceutical treatments for diabetes management. (37)

Unlike blood glucose measurements, which provide a snapshot of real-time blood sugar levels, HbA1c offers a comprehensive view of glycemic control over an extended period. It is important to realize that blood glucose monitoring (via glucose monitors) and HbA1c relay different types of information regarding glucose control, and both are important in understanding and managing dysglycemia. The estimated average glucose (eAG), reported in the same units as blood glucose, can be calculated from HbA1c. This can help individuals correlate the broader meaning of HbA1c to their day-to-day readings on glucose monitors. (37)

HbA1c Testing in Functional Medicine

For nondiabetic patients, functional healthcare providers strategically monitor HbA1c trends to facilitate early identification of dysglycemia, allowing for timely intervention to prevent and reverse prediabetes before it progresses to diabetes. This proactive approach aligns with the core tenets of functional medicine, emphasizing personalized, preventive healthcare.

For individuals in prediabetic and diabetic states, HbA1c is a crucial marker in a comprehensive glycemic control and metabolic dysfunction assessment. Integrating HbA1c with other diagnostic tools such as fasting blood glucose, 2-hour oral glucose tolerance test (OGTT), continuous glucose monitoring (CGM), fasting insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), lipid panels, and inflammation markers provides a nuanced understanding of glucose control, insulin function, and cardiovascular well-being. This multifaceted approach allows healthcare providers to tailor treatment plans to the individual's unique physiological profile, addressing glycemic control and identifying potential contributors to metabolic dysfunction. Functional medicine practitioners can use an array of tests and measurements to discern the intricate interplay of factors influencing metabolic health, fostering a more holistic and patient-centered approach to diabetes management.

Interpreting HbA1c Test Results

The ranges in the table below are used to interpret HbA1c test results. Within the prediabetic range, the higher the A1c, the greater the risk of developing type 2 diabetes. Within the diabetic range, the higher the A1c, the greater the risk of developing diabetic complications.

The goal for most nonpregnant adults with diabetes is to maintain HbA1c below 7%, as this has been associated with a reduced risk of diabetes-associated complications and hypoglycemia. However, individualized targets may vary based on factors such as age, overall health, and other medical conditions. For example, a less stringent HbA1c target of less than 8% is recommended for patients with a limited life expectancy or where the potential risks of treatment are greater than the benefits (e.g., high risk of severe hypoglycemia). Conversely, the American Diabetes Association (ADA) states that more stringent HbA1c goals of less than 6.5% may be appropriate for select patients if achievable without causing significant hypoglycemia or other adverse events. (5, 6)

Dietary and Lifestyle Modifications Based on HbA1c

A functional medicine approach to treating diabetes is rooted in a patient-centered paradigm, emphasizing comprehensive care beyond just pharmaceutical interventions. Educating patients on the importance of lifestyle and dietary habits is a cornerstone to effective glycemic control and improvement of patient outcomes. The findings of a 2021 study underscore the importance of patient empowerment and education; fostering self-efficacy and informed decision-making through diabetes education leads to significant improvements in HbA1c in patients with type 2 diabetes.

Diet

Clinical studies consistently support the efficacy of specific dietary strategies in managing diabetes, with a notable impact on improving HbA1c levels. One prominent approach is the adoption of a low-carbohydrate diet. A study published in JAMA found that individuals with type 2 diabetes following a low-carbohydrate diet experienced significant improvements in glycemic markers (i.e., reductions in HbA1c and fasting plasma glucose) and weight loss compared to individuals eating a usual diet.

Additionally, the Mediterranean diet has demonstrated significant benefits for individuals with diabetes. A landmark study, the PREDIMED trial, revealed that adherence to a Mediterranean diet rich in olive oil or nuts led to a substantial reduction in the incidence of cardiovascular events among participants with diabetes. The diet emphasizes whole grains, fruits, vegetables, and healthy fats, showcasing its potential to positively impact HbA1c levels and mitigate cardiovascular risk factors.

Furthermore, plant-based (i.e., vegetarian and vegan) diets have garnered attention for their favorable effects on diabetes management. Diets that emphasize whole grains, vegetables, fruits, and legumes improve body weight, insulin sensitivity, and beta-cell function, bettering blood glucose, body weight, lipid concentrations, and blood pressure.

Exercise

Exercise offers myriad benefits for individuals with diabetes, such as managing body weight; improving blood pressure, lipid profiles, and insulin sensitivity; and reducing blood glucose levels. Aerobic and resistance exercises are equally good at lowering HbA1c levels by 0.7% in people with diabetes. Pahra et al. demonstrated that walking (1,500-1,600 steps) three times a day for 15 minutes after meals decreased HbA1c levels by 0.9% after eight weeks. This is enough to shift HbA1c from the diabetic into the normal range! (38)

Stress

The physiological stress response involves the release of stress hormones, such as cortisol and adrenaline, triggering an increase in blood glucose levels. This is part of the body's natural "fight or flight" response, preparing for heightened energy demands. However, in the context of chronic stress, these elevated glucose levels persist, leading to sustained hyperglycemia. Research indicates a clear association between chronic stress, insulin resistance, and poor glycemic control, reflected in higher HbA1c levels. (41, 45)

Implementing stress management techniques emerges as an effective method to improve HbA1c levels. Studies have demonstrated that mindfulness-based stress reduction (MBSR), mindfulness meditation, and mindfulness-based cognitive therapy (MBCT) can positively impact glycemic control, improving HbA1c by roughly 0.7%.

Sleep

Studies consistently demonstrate that the quality and quantity of sleep affect metabolism and diabetes management. Insufficient sleep (less than 7-8 hours per night) and poor sleep hygiene are linked to increased HbA1c levels in adults with type 2 diabetes. Insulin sensitivity decreases by 25-30% after 4-5 nights of insufficient sleep. (15)

These findings emphasize the importance of prioritizing sufficient and restorative sleep in diabetes care. Doctors should not only be encouraged to counsel their patients on practicing good sleep hygiene techniques but also screen their prediabetic and diabetic patients for sleep disorders. In one study, CPAP therapy was found to significantly improve HbA1c and long-term glycemic control in patients with type 2 diabetes and obstructive sleep apnea.

Monitoring and Adjusting Diabetes Management

The U.S. Preventive Service Task Force (USPSTF) recommends that adults aged 35-70 years who are overweight or obese be screened for prediabetes and type 2 diabetes annually. The CDC recommends that all adults over age 45 – or under age 45 with at least one risk factor for diabetes – be screened for diabetes with an HbA1c test.

Per ADA guidelines, HbA1c should be measured twice yearly in patients with stable diabetes and at least four times a year in patients with diabetes who have frequent glucose fluctuations, are not meeting their HbA1c goals, or have changed their diabetes treatment. (23)

Regular monitoring of HbA1c allows for ongoing assessment and adjustments to treatment plans as needed. Treatment plans for individuals with diabetes are often adjusted based on HbA1c results. When HbA1c levels exceed the target range, healthcare providers may consider medication adjustments and additional lifestyle interventions to optimize diabetes management. Conversely, patients meeting their HbA1c targets may be able to reduce their dependency on pharmaceutical and nutraceutical interventions to maintain stable blood sugar levels. Patients should never change their treatment regimens without consulting their healthcare provider.

Challenges and Considerations in HbA1c Testing

With the establishment of the National Glycohemoglobin Standardization Program (NGSP), the accuracy of the HbA1c test has continued to become more precise over time. However, certain factors can influence the accuracy of this test and need to be considered when interpreting lab results. Hemoglobin variants, anemias, chronic kidney disease, pregnancy, and blood transfusions can affect red blood cell concentration and turnover rate, resulting in HbA1c discrepancies. When HbA1c values do not align with eAG levels, alternative markers of glycemic control should be ordered to confirm results. (13)

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HbA1c Testing: Key Takeaways

HbA1c is a convenient and affordable testing method for effective diabetes diagnosis and management. This marker provides a longitudinal view of glycemic control, representing one aspect of metabolic health that can aid healthcare providers in tailoring personalized treatment plans. Regular HbA1c assessments enable a nuanced understanding of long-term glucose control and help guide prognostic and treatment decisions for patients with insulin resistance, prediabetes, and diabetes. Using HbA1c as a diagnostic tool to monitor patients with or at risk for diabetes is one aspect of a functional, patient-centered strategy to optimize cardiometabolic health.