What does A1c (hemoglobin A1c) measure in patients with diabetes or those at risk of developing diabetes?

What A1C Measures

A1C measures average blood glucose levels over the preceding 2-3 months by quantifying the percentage of hemoglobin that has become glycated (bound to glucose). 1

Mechanism and Timeframe

• A1C reflects the glycation of hemoglobin in red blood cells, which occurs continuously over the lifespan of erythrocytes (approximately 120 days). 1, 2
• The test provides an indirect measure of average glycemia rather than a direct glucose measurement. 1
• Because red blood cells have a lifespan of about 120 days, A1C integrates glucose exposure over approximately 2-3 months, with more recent glucose levels contributing slightly more to the result. 1

Clinical Interpretation: A1C to Average Glucose Conversion

The relationship between A1C and mean plasma glucose is well-established, based on the ADAG study of 507 adults with approximately 2,700 glucose measurements per A1C reading: 1

• A1C of 6% = mean glucose of 126 mg/dL (7.0 mmol/L) 1
• A1C of 7% = mean glucose of 154 mg/dL (8.6 mmol/L) 1
• A1C of 8% = mean glucose of 183 mg/dL (10.2 mmol/L) 1
• A1C of 9% = mean glucose of 212 mg/dL (11.8 mmol/L) 1
• A1C of 10% = mean glucose of 240 mg/dL (13.4 mmol/L) 1

What A1C Does NOT Measure

A1C has critical limitations that clinicians must recognize: 1

• Does not measure glycemic variability (day-to-day or hour-to-hour glucose fluctuations). 1, 3
• Does not detect hypoglycemia or provide information about low glucose episodes. 1, 3
• Does not capture acute glucose changes or real-time glucose levels. 2

Critical Conditions That Invalidate A1C

A1C becomes unreliable and should NOT be used in the following situations: 1

• Hemolytic anemia or any condition causing increased red blood cell turnover. 1
• Recent blood transfusion (within 2-3 months). 1
• Pregnancy (second and third trimesters due to increased red blood cell turnover). 1
• Sickle cell disease (HbSS) or other homozygous hemoglobin variants—A1C cannot be measured at all in these patients since they lack HbA. 1
• End-stage kidney disease on dialysis. 1
• Use of erythropoiesis-stimulating agents (e.g., EPO therapy). 1
• Glucose-6-phosphate dehydrogenase deficiency. 1

In these situations, use alternative monitoring methods: 1, 4

• Fructosamine or glycated serum albumin (reflects 1-2 weeks of glycemia). 1
• Self-monitoring of blood glucose (SMBG). 1
• Continuous glucose monitoring (CGM). 1
• Use only plasma glucose criteria for diagnosis and monitoring decisions. 1

Assay Standardization Requirements

• Only use A1C assays certified by the National Glycohemoglobin Standardization Program (NGSP) and traceable to the DCCT reference method. 1
• Point-of-care A1C testing must use FDA-approved devices at CLIA-certified laboratories performing moderate complexity testing or higher. 3
• Most assays in the U.S. are accurate for heterozygous hemoglobin variants (e.g., sickle cell trait), but homozygous variants render A1C unmeasurable. 1

Relationship to Diabetes Complications

• A1C is strongly linked to diabetes complications, with robust epidemiologic evidence showing direct relationships between A1C levels and risk of microvascular complications (retinopathy, nephropathy, neuropathy). 1, 2
• The correlation is stronger than that observed for individual glucose measurements, which is why A1C has become the gold standard for monitoring. 2
• Clinical trials (particularly the DCCT) demonstrated that lowering A1C reduces the development and progression of microvascular disease. 1, 2