ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1676168
Association between changes in obesity status and neuropsychiatric health and brain structure in different glucose status
Provisionally accepted
- 1The First Hospital of Putian City Department of Neurology, Putian, China
- 2University of Science and Technology of China, Hefei, China
- 3The First Affiliated Hospital of USTC Department of Neurology, Hefei, China
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1 Background: Obesity is a major global health challenge, linked to 2 cardiometabolic and neuropsychiatric disorders through mechanisms such as 3 inflammation and insulin resistance. However, little is known about how 4 adiposity and its longitudinal changes interact with glycemic status to shape 5 neuropsychiatric health and brain structural vulnerability. Clarifying these 6 relationships is of high importance, as both obesity and dysglycemia are 7 modifiable risk factors that may jointly accelerate brain aging and psychiatric 8 disorders. 9 Methods: Using UK Biobank data (n=423,750, with 32,551 having brain MRI), 10 we examined associations between obesity indicators (body mass index [BMI], 11 waist circumference [WC], body fat percentage [BFP]) and changes in obesity 12 status with incident neuropsychiatric disorders (stroke, dementia, Parkinson's 13 disease, depression, anxiety) and brain structural measures. Participants were 14 stratified by glycemic status—normal glucose regulation (NGR), prediabetes 15 (Pre-DM), and diabetes (DM)— based on American Diabetes Association 16 criteria. Cox proportional hazards and linear regression models were used. 17 Results: Higher BMI, WC, and BFP were associated with increased risks of 18 depression and anxiety across all glycemic groups, particularly in NGR. 19 Abdominal obesity was linked to Parkinson's disease risk in NGR. Conversely, 20 BMI showed an inverse association with dementia in NGR, possibly due to 21 reverse causality. Persistent obesity and weight gain were associated with 22 higher depression and anxiety risks in NGR. In diabetes, higher BFP was 23 strongly linked to reduced grey matter, thalamus, and hippocampus volumes 24 and increased WMHs. This association with BFP represented the most robust 25 imaging signal, highlighting the pronounced vulnerability of brain structure to 26 excess adiposity in diabetes. Similar but weaker patterns were observed in 27 prediabetes and NGR. 28 Conclusion: Obesity, particularly persistent or increasing adiposity, adversely 29 affects neuropsychiatric health and brain structure, and these effects are 30
Keywords: Obesity, neuropsychiatric disorders, brain structure, Glycemic status, UK Biobank
Received: 30 Jul 2025; Accepted: 12 Sep 2025.
Copyright: © 2025 Chen, Zhang, Lin, Qiu, Zou, Liu, Huang and Wen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ping Chen, edmunc@163.com
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