Nathan 2008: ADAG Study - Translating A1C to Average Glucose

Background

Dr. David M. Nathan and the A1C-Derived Average Glucose (ADAG) Study Group published this landmark study in Diabetes Care (PMID: 18540046), establishing the mathematical relationship between HbA1c and average glucose.

Study Design

Design: Prospective observational study Population: 507 participants (268 type 1 diabetes, 159 type 2 diabetes, 80 non-diabetic) Methods:

• •HbA1c measured monthly for 3 months
• •Continuous glucose monitoring (CGM) for 48 hours each month
• •Self-monitored blood glucose 7+ times daily
• •Linear regression to derive relationship

Key Findings

The ADAG formula:

eAG (mg/dL) = 28.7 × A1C − 46.7
eAG (mmol/L) = 1.59 × A1C − 2.59

Correlation: r = 0.92 (excellent)

A1C (%)	eAG (mg/dL)	eAG (mmol/L)
5.0	97	5.4
6.0	126	7.0
7.0	154	8.6
8.0	183	10.2
9.0	212	11.8
10.0	240	13.4

Mechanistic Insights

HbA1c reflects average glucose exposure over RBC lifespan (~120 days), weighted toward recent weeks. The linear relationship allows conversion to glucose units more intuitive for patients.

Limitations:

• •Individual variation exists (±15 mg/dL at any A1C)
• •Conditions affecting RBC lifespan alter the relationship

Clinical Implications

The eAG conversion allows patients to understand their A1C in familiar glucose units. However, eAG is a population average—individual variation means it may not match a specific patient's true average.

Metabolic Health Perspective

For metabolic optimization, direct glucose measurement (CGM or frequent monitoring) provides superior insight into patterns, variability, and postprandial spikes that eAG cannot capture. A1C/eAG remain useful for long-term trending.