T2D, Prediabetes Accelerate Brain Aging, but Healthier Lifestyle May Counteract the Association

Type 2 diabetes (T2D) and prediabetes are associated with accelerated brain aging, particularly among men and persons with poor cardiometabolic health, according to a new study from the Karolinska Institute in Sweden. However, a healthy lifestyle, characterized by increased physical activity and no smoking or heavy drinking, may counteract this.

T2D is a known risk factor for dementia, but less is known about how T2D and prediabetes impact brain aging in persons without dementia, researchers reported in the journal Diabetes Care. To examine this further, as well as whether the association between T2D and prediabetes and older brain age can be attenuated by modifiable lifestyle behaviors, investigators assessed data from 31 229 dementia-free adults aged 40 to 70 years from the UK Biobank.

Glycemic status (ie, normoglycemia, prediabetes, or diabetes) was based on medical history, medication use, and HbA_1c levels measured at baseline. Researchers also collected information on cardiometabolic risk factors (eg, obesity, hypertension, low HDL, and high triglycerides) and lifestyle behaviors (eg, smoking, drinking, exercise) at baseline. Over the 11-year follow-up period, all participants had 1 or 2 brain MRI scans. Investigators estimated participants’ brain age using a machine learning model based on 1079 brain MRI phenotypes, which was then used to calculate brain age gap (BAG; ie, brain age minus chronological age), according to the study.

At baseline, 43.3% of the cohort (n=13 518) had prediabetes and 3.7% (n=1149) were diagnosed with T2D, researchers reported.

Results showed that, compared with normoglycemia, prediabetes (β = 0.22, 95% CI 0.10-0.34) and T2D (β = 2.01, 95% CI 1.70-2.32) were associated with significantly higher BAG. Specifically, on average, brain age was 0.50 years older than the chronological age of participants with prediabetes and 2.29 years older than the age of those with T2D. Among study participants with poor glycemic control (HbA_1c of 8% or higher), BAG rose up to 4.18 years. Researchers reported that when used as a continuous variable, HbA_1c was associated with significantly higher BAG (β = 0.77, 95% CI 0.65-0.90). In addition, T2D was associated with significant increase in BAG over time (β = 0.27, 95% CI 0.01-0.53), according to investigators.

In stratified analyses, researchers observed that the association between T2D and higher BAG was more pronounced among men (β = 2.32, 95% CI 1.90-2.74) than women (β = 1.51, 95% CI 1.04-1.99), and among those with a 2 or more cardiometabolic risk factors (β = 2.20, 95% CI 1.74-2.66) compared with 0-1 risk factors (β = 1.91, 95% CI 1.45-2.36).

In joint exposure analysis, investigators found that an optimal healthy lifestyle significantly attenuated the association between T2D and BAG. On average, the brain age was 0.78 years older than the chronological age of participants with T2D and an optimal lifestyle compared with 2.46 years older than those with a nonoptimal lifestyle. “Therefore, healthy lifestyle was related to a 1.68-year reduction BAG,” investigators wrote.

“Diabetes and even prediabetes were related to significantly older brain age in relation to chronological age, and diabetes was further associated with significant widening of the gap between brain and chronological age over time,” the authors wrote. “Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health.”

Reference: Dove A, Wang J, Huang H, et al. Diabetes, prediabetes, and brain aging: The role of healthy lifestyle. Diabetes Care. Published online August 28, 2024. doi:10.2337/dc24-0860