Among 97 adults with severe obesity (BMI 35-73), each one-unit rise in HbA1c corresponded to a brain that looked about 1.6 years older by the ENIGMA MRI model and 0.9 years older by the Pyment model, after adjusting for age, sex and race. The ENIGMA association survived robust regression (B = 1.70, p = .002); the Pyment association did not (p = .13). BMI, hypertension and hyperlipidemia showed no link to brain age gap.
The glucose signal fits a larger body of work tying dysglycemia to brain atrophy, vascular injury and dementia risk, and it suggests blood sugar control may matter more for brain aging than weight alone once obesity is already severe. The null BMI result deserves caution: a sample restricted to BMI 35 and above leaves little variation to detect an effect, which the authors acknowledge. Other limits are substantial. The design is cross-sectional, so it cannot show that glucose drives brain aging rather than the reverse or that both share a cause. With 97 participants, results across the two brain age models diverged, and subgroup findings rest on small numbers. There is no comparison group of leaner adults, and brain age gap is still a research biomarker, not a clinical test. This is a preprint, not yet peer reviewed, so findings may change. The practical takeaway is modest and consistent with existing advice: people with severe obesity have another reason to monitor HbA1c and discuss glycemic control with their doctor. Incremental and hypothesis-generating, not a shift in understanding.