The discovery of HbA1c dates back to the late 1950s. In 1958, Huisman and Meyering first separated HbA1c from other forms of hemoglobin using chromatography . Later, in 1968, Bookchin and Gallop identified that HbA1c is formed by the attachment of glucose to the N-terminal valine of the hemoglobin beta chain . In 1969, Rahbar discovered that HbA1c levels were elevated in patients with diabetes . This finding laid the foundation for using HbA1c as a marker for diabetes management.
Hemoglobin is a protein in red blood cells responsible for transporting oxygen from the lungs to the rest of the body. It consists of four subunits: two alpha and two beta chains. HbA1c is formed when glucose in the bloodstream binds non-enzymatically to the N-terminal valine of the beta chains of hemoglobin . This process, known as glycation, occurs over the lifespan of the red blood cell, which is approximately 120 days .
The primary function of hemoglobin is to carry oxygen, but the glycation of hemoglobin to form HbA1c does not affect its oxygen-carrying capacity. Instead, HbA1c serves as an indicator of average blood glucose levels over the past two to three months . This is because the glycation process is irreversible, and the level of HbA1c reflects the average glucose concentration during the lifespan of the red blood cells .
HbA1c is widely used in clinical practice to monitor and diagnose diabetes. The American Diabetes Association (ADA) and other diabetes organizations recommend using HbA1c levels to assess long-term glycemic control in diabetic patients . An HbA1c level of 6.5% or higher is typically used as a diagnostic criterion for diabetes . Regular monitoring of HbA1c helps healthcare providers adjust treatment plans to achieve optimal blood glucose control and reduce the risk of diabetes-related complications .
The measurement of HbA1c has evolved over the years. Initially, various methods were used, leading to inconsistencies in results. To address this, the National Glycohemoglobin Standardization Program (NGSP) was established in 1996 to standardize HbA1c measurements to those used in the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) . The International Federation of Clinical Chemistry (IFCC) has also developed a reference system to ensure metrological traceability .