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Elevated HbA1c is associated with advanced brain age in severe obesity
Medrxiv : the Preprint Server for Health Sciences
|June 12, 2026
Summary
Elevated HbA1c is linked to advanced brain aging in severe obesity. This association was most prominent in individuals with prediabetes and diabetes, not BMI or hypertension.
Area of Science:
- Neuroimaging and Machine Learning
- Cardiometabolic Health and Aging
Background:
- Brain-predicted age (BAG) estimates biological brain aging using MRI.
- Higher BAG signifies accelerated aging and is linked to cognitive decline.
- Cardiometabolic risk factors are associated with cognitive impairment but their link to BAG in severe obesity is unclear.
Purpose of the Study:
- To investigate the association between cardiometabolic risk factors and BAG in adults with severe obesity.
- To examine relationships between HbA1c, BMI, hypertension, hyperlipidemia, and BAG.
Main Methods:
- Structural MRI data from 97 adults with severe obesity (BMI 35-73) were analyzed.
- Brain age gap (BAG) was calculated using ENIGMA and Pyment models.
- Associations with HbA1c, BMI, hypertension, and hyperlipidemia were assessed using regression, adjusting for age, sex, and race.
Main Results:
- Elevated HbA1c was significantly associated with greater BAG in both linear and robust regression models.
- Associations between HbA1c and BAG were stronger in individuals with prediabetic and diabetic levels.
- BMI, hypertension, and hyperlipidemia were not significantly associated with BAG in this severely obese cohort.
Conclusions:
- Elevated HbA1c is a significant correlate of accelerated brain aging (BAG) in severe obesity.
- The link between HbA1c and BAG is most pronounced at clinically elevated glucose levels.
- No significant associations were found between BAG and BMI, hypertension, or hyperlipidemia in this sample.
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