HbA1c as a Continuous Marker of Microvascular Vulnerability: Development of a Non-Linear Risk Framework in a...

Area of Science:

• Endocrinology
• Metabolic Health
• Diabetes Research

Background:

• Glycated hemoglobin (HbA1c) is standard for diabetes diagnosis and monitoring.
• Current interpretation relies on fixed thresholds, potentially overlooking risks in sub-diagnostic ranges.
• This study explores HbA1c as a continuous variable for individualized risk assessment.

Purpose of the Study:

• To translate the non-linear relationship between HbA1c and microvascular complications into an individualized risk framework.
• To analyze the glycemic risk continuum beyond fixed diagnostic thresholds.
• To investigate the clinical relevance of the HbA1c sub-diagnostic interval (5.5-6.4%) for risk stratification.

Main Methods:

• Cross-sectional observational study of a real-world clinical cohort.
• HbA1c analyzed as a continuous variable, assessing associations with metabolic parameters and complication burden.
• Restricted cubic spline logistic regression used to model non-linear risks and analyze the HbA1c gray zone.

Main Results:

• HbA1c demonstrated a strong continuous association with fasting plasma glucose.
• A positive association was found between HbA1c and cumulative diabetes-related complication burden.
• Non-linear modeling revealed progressive complication risk increase below diagnostic thresholds, with accelerated risk in the 5.5-6.4% HbA1c range.

Conclusions:

• HbA1c functions as a continuous, non-linear marker of metabolic stress.
• Biologically meaningful increases in complication risk emerge below traditional diagnostic thresholds.
• Findings support a glycemic risk continuum and highlight the utility of the sub-diagnostic HbA1c interval for early preventive strategies.