Rohlfing 2002: HbA1c-Glucose Relationship

Background

Dr. Curt L. Rohlfing and colleagues published this study in Diabetes Care (PMID: 12196384), an early effort to define the relationship between HbA1c and mean plasma glucose that would later inform the ADAG study.

Study Design

Design: Retrospective analysis Population: Patients with type 1 and type 2 diabetes Data: HbA1c measurements paired with self-monitored blood glucose (SMBG) averages Analysis: Linear regression modeling

Key Findings

Relationship between HbA1c and mean glucose:

• •Strong linear correlation demonstrated
• •Each 1% increase in HbA1c ≈ 35 mg/dL increase in mean glucose

Early conversion estimates:

HbA1c (%)	Estimated Mean Glucose (mg/dL)
6.0	~120
7.0	~155
8.0	~190
9.0	~225

Limitations identified:

• •Based on SMBG (not CGM)
• •Individual variation substantial
• •Different glucose profiles can yield same HbA1c

Mechanistic Insights

HbA1c reflects glycation of hemoglobin over RBC lifespan:

• •Non-enzymatic attachment of glucose to hemoglobin
• •Proportional to ambient glucose concentration
• •Integrates glucose exposure over ~120 days
• •Weighted toward recent weeks (newer RBCs)

Clinical Implications

This study laid groundwork for:

• •Understanding HbA1c in glucose units
• •Later ADAG study with CGM validation
• •Clinical translation of HbA1c to "average glucose"

Metabolic Health Perspective

While the HbA1c-glucose relationship is useful, this study acknowledged limitations that remain relevant: individual variation means estimated glucose may not match a patient's actual average. For metabolic optimization, direct glucose monitoring provides superior insight.