The A1c test, formally known as hemoglobin A1c or HbA1c, measures average blood glucose levels over an extended period. It reflects the amount of glucose chemically attached to hemoglobin, the oxygen-carrying protein within red blood cells. Since red blood cells circulate for approximately two to three months, the A1c value offers a retrospective view of average blood sugar control, unlike a finger-stick test which captures only a single moment in time. This measure has transformed diabetes management, progressing from a biochemical curiosity to a globally accepted clinical standard.
Identifying Glycated Hemoglobin
The A1c test began as a laboratory finding, years before its importance to diabetes was understood. In 1958, scientists first separated a minor component of human hemoglobin using column chromatography. This fraction was distinct from the main hemoglobin components and was labeled as HbA1c.
At this stage, the molecule was observed during routine protein analysis but was not recognized as a direct marker of blood sugar levels. Further work in the late 1960s characterized the component as a glycoprotein.
A significant observation occurred in 1968 when a research team noted that this “abnormal fast-moving hemoglobin band” was present in elevated concentrations in the blood of individuals with diabetes. The link was primarily a correlation, and the mechanism by which glucose non-enzymatically attached to the hemoglobin molecule was not yet fully characterized.
Establishing the Clinical Correlation
The transition to a practical medical test occurred in the 1970s with the realization of its clinical significance. Researchers confirmed that the formation of glycated hemoglobin was a slow, non-enzymatic reaction. This meant the amount of A1c produced was directly proportional to the average glucose concentration in the blood over time.
In 1976, a proposal suggested using the HbA1c measurement for monitoring long-term glucose control in patients with diabetes. Previously, doctors relied on fasting glucose tests or urine sugar measurements, which only provided a snapshot of the patient’s condition. The stability of the A1c molecule, reflecting the 120-day lifespan of the red blood cell, made it a superior indicator of chronic hyperglycemia.
Clinicians now had an objective measure reflecting two to three months of a patient’s actual glucose exposure. The test allowed assessment of the effectiveness of a treatment regimen and adherence to diet. Evidence accumulated throughout the decade established a clear relationship between higher A1c levels and a greater risk of long-term diabetic complications.
Standardization and Widespread Adoption
Despite the scientific understanding established in the 1970s, A1c testing did not become a widespread, reliable tool overnight due to inconsistent measurement methods. Different laboratories used different chemical assays, leading to incomparable and unreliable results across institutions. This inconsistency was a major barrier to its adoption.
The turning point came with the Diabetes Control and Complications Trial (DCCT), which ran from 1983 to 1993. This study demonstrated that maintaining lower A1c levels significantly reduced the risk of developing microvascular complications, such as damage to the eyes, kidneys, and nerves. The DCCT validated the A1c test as the standard for monitoring diabetes control and predicting long-term outcomes.
Following the DCCT, a unified reporting system was necessary. In 1996, the National Glycohemoglobin Standardization Program (NGSP) was established to standardize A1c test results worldwide. The NGSP ensured that all commercial laboratory methods produced results traceable to the assay used in the DCCT, improving reliability and comparability across different labs.
The final step toward widespread adoption was the official recommendation of A1c for diagnosis. Building on standardization efforts and clinical evidence, the American Diabetes Association (ADA) officially recommended the A1c test as a diagnostic criterion for diabetes in 2010. The recommended threshold of 6.5% or higher marked the A1c test’s full transition to a routine tool for screening, diagnosis, and management.