Addressing shortfalls of laboratory HbA_1c using a model that incorporates red cell lifespan

Area of Science:

• Endocrinology
• Metabolic Diseases
• Diabetes Research

Background:

• Standard laboratory HbA1c (glycated hemoglobin) may not accurately predict diabetes complications.
• Intracellular glucose exposure in susceptible organs is a key factor in complication development.

Purpose of the Study:

• To develop a novel glycaemic measure, adjusted HbA1c (aHbA1c), that better reflects intracellular glucose exposure.
• To evaluate the clinical relevance of aHbA1c compared to laboratory HbA1c in predicting diabetes complications.

Main Methods:

• Utilized six months of continuous glucose monitoring data from 51 type 1 diabetes (T1D) and 80 type 2 diabetes (T2D) patients.
• Employed a kinetic model of glucose and HbA1c to estimate red blood cell (RBC) lifespan and calculate person-specific aHbA1c.
• Compared aHbA1c values with concurrent laboratory HbA1c measurements.

Main Results:

• Median RBC lifespan was approximately 100 days in both T1D and T2D cohorts.
• Clinically relevant differences were observed between aHbA1c and laboratory HbA1c.
• The absolute difference ranged from 3.9-5.3 mmol/mol (0.4-0.5%) in T1D and T2D patients, respectively.

Conclusions:

• Laboratory HbA1c may underestimate or overestimate diabetes complication risks.
• Adjusted HbA1c (aHbA1c) offers a potentially more accurate reflection of glucose exposure relevant to complications.
• This refined glycaemic measure may have significant future clinical implications for diabetes management and risk stratification.