Hemoglobin A1cEdit
Hemoglobin A1c, commonly abbreviated HbA1c, is a laboratory measure that reflects average blood glucose levels over roughly the previous two to three months. It is the glycated form of hemoglobin A and is formed when glucose binds to the N-terminal valine of the beta chain of the hemoglobin molecule in red blood cells. Because red blood cells have a lifespan of about 120 days, the HbA1c value provides a convenient, integrated readout of long-term glycemic exposure, rather than short-term fluctuations after meals.
Over the past several decades, HbA1c has become a cornerstone of both diagnosing diabetes and monitoring glycemic control in people with established diabetes. Clinicians and policymakers alike favor a single, standardized test that does not require fasting and that can be administered in routine primary care settings. The test is reported as a percentage of total hemoglobin and is measured using several technologies, with international standardization efforts coordinated by the National Glycohemoglobin Standardization Program NGSP and the International Federation of Clinical Chemistry and Laboratory Medicine IFCC to ensure consistency across laboratories. To navigate different reporting systems, clinicians often convert between NGSP (DCCT-aligned) percentages and IFCC (SI) units.
Measurement and standardization
HbA1c measurement relies on the predictable relationship between mean blood glucose and the fraction of hemoglobin that becomes glycated over time. The stability of this relationship depends on the lifespan of circulating red blood cells; conditions that shorten or lengthen erythrocyte lifespan can bias HbA1c results. As a result, certain clinical circumstances can affect accuracy, and clinicians must interpret HbA1c in the context of the patient’s overall health.
There are several assay methods in routine use, including high-performance liquid chromatography HPLC and various immunoassay or enzymatic platforms. Despite methodological differences, the NGSP and IFCC frameworks aim to align results to long-standing reference points. Conversion between DCCT-aligned percent values and IFCC-aligned mmol/mol values is common in practice; one DCCT-percent value roughly corresponds to a specific IFCC mmol/mol value, and laboratories typically provide both representations or a conversion table.
Interfering factors include iron deficiency anemia, pregnancy, acute blood loss, certain kidney diseases, and particularly a range of hemoglobin variants (for example, some sickle-cell conditions and thalassemias). In such situations, HbA1c may overestimate or underestimate average glucose, and alternative tests or supplemental data may be appropriate. In addition, race and ethnicity have been observed to influence the distribution of HbA1c values at similar average glucose levels in some studies, though the exact mechanisms are not fully settled. These nuances are central to ongoing debates about universal use of HbA1c for screening and diagnosis in diverse populations. For a broader look at related concepts, see Glycation and Hemoglobin.
Clinical use: diagnosis and management
HbA1c serves two broad clinical roles: diagnosis of diabetes and ongoing management of glycemic control in people with hyperglycemia or established diabetes.
Diagnosis and screening: The American Diabetes Association ADA and other major bodies have endorsed specific HbA1c thresholds for diagnosing diabetes. An HbA1c of 6.5% (DCCT-aligned) or 48 mmol/mol (IFCC) is widely used as a diagnostic criterion for diabetes, while an HbA1c from 5.7% to 6.4% (39–46 mmol/mol) is described as prediabetes or increased risk. HbA1c testing is valued for convenience and standardization, but some guidelines also acknowledge fasting plasma glucose FPG or the oral glucose tolerance test OGTT as alternative or complementary approaches, especially in settings where more precise risk stratification is needed. See Prediabetes and Diabetes mellitus for broader context. In pregnancy, HbA1c is less reliable for diagnosing gestational diabetes, and specific obstetric guidelines favor other diagnostic approaches, such as the OGTT, when indicated. See Gestational diabetes.
Monitoring and targets: For many nonpregnant adults with diabetes, a commonly cited target is an HbA1c below 7%, balancing long-term risk reduction with the risk of hypoglycemia. Individual targets may be adjusted based on age, comorbidities, and risk tolerance, with more stringent goals for some patients and more relaxed goals for those with significant frailty or complex illness. HbA1c testing is typically performed every three months when starting or changing therapy, and every six months when control is stable. For practical purposes, HbA1c serves as a proxy for cumulative glycemic exposure that correlates with the risk of microvascular complications over time. See Diabetes mellitus and Diabetes Control and Complications Trial for foundational work that links glycemic exposure to outcomes.
Practical considerations: Because HbA1c results do not depend on fasting and reflect longer-term control, the test is particularly attractive in busy primary care settings and in populations where fasting samples are logistically challenging. However, clinicians may supplement HbA1c data with fasting glucose measurements or OGTT results when there are concerns about accuracy or individual risk profiles. See also Fasting plasma glucose and Oral glucose tolerance test.
Limitations, debates, and population considerations
Several controversies surround HbA1c as a diagnostic and management tool, and they are routinely discussed in professional forums and guideline panels:
Population and individual variability: HbA1c distribution at a given average glucose level can differ across populations. Factors such as red blood cell turnover, race/ethnicity, and genetic variation can influence HbA1c independently of average glucose. While this can improve risk stratification for some, it can also lead to misclassification in others. In response, some clinicians advocate using HbA1c as part of a broader assessment rather than as a stand-alone diagnostic criterion in all patients. See Ethnicity and health and Hemoglobin variant for related discussions.
Hematologic conditions and pregnancy: Conditions that alter hemoglobin or red blood cell lifespan—such as iron deficiency anemia Iron-deficiency anemia, sickle-cell disease Sickle-cell disease, thalassemia Thalassemia, or pregnancy—can bias HbA1c results. In such cases, alternative measures of glycemia or direct assessment of glucose exposure over time may be warranted.
Diagnostic thresholds and alternatives: HbA1c thresholds provide a practical, standardized framework, but some researchers and clinicians argue for complementary testing (FPG, OGTT) to improve sensitivity and specificity in diverse populations. The choice of criteria can influence rates of diagnosis and the perceived burden of disease, which has implications for healthcare policy and resource allocation. See Oral glucose tolerance test and Fasting plasma glucose for context.
Policy and practice implications: From a policy standpoint, proponents of HbA1c-driven screening emphasize efficiency, standardization, and alignment with long-term outcomes, arguing that a single, well-standardized test improves population health management and reduces unnecessary repeat testing. Critics warn against over-reliance on a single metric, particularly in groups where HbA1c may misrepresent true glycemic exposure. The ongoing policy discourse weighs cost, access, and the incentives created by widespread testing and guideline-driven care. See Diabetes and NGSP for related governance aspects.