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Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis
Tianqi Zhang, Marnie Shaw, Nicolas Cherbuin
Diabetes Metab J. 2022;46(5):781-802.   Published online March 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0189
  • 16,820 View
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  • 63 Web of Science
  • 73 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM.
Methods
PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression.
Results
A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration.
Conclusion
T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

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Drug/Regimen
Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus
Jae Hyun Bae, Hyung Jin Choi, Kang Ik Kevin Cho, Lee Kyung Kim, Jun Soo Kwon, Young Min Cho
Diabetes Metab J. 2020;44(2):248-259.   Published online November 4, 2019
DOI: https://doi.org/10.4093/dmj.2019.0018
  • 17,519 View
  • 291 Download
  • 23 Web of Science
  • 25 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.

Methods

In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet.

Results

Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P<0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P<0.05), and visual cortex (food vs. nonfood, P<0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P<0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P<0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P<0.05).

Conclusion

Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.

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    Obesity Reviews.2026;[Epub]     CrossRef
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    Kayla Flanagan, Luiza Bonfim Pacheco, Mengxia Gao, Antonio Verdejo-Garcia
    Reviews in Endocrine and Metabolic Disorders.2026;[Epub]     CrossRef
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    Xiaoke Dou, Lei Zhao, Jing Li, Yaqiu Jiang
    Frontiers in Neuroscience.2025;[Epub]     CrossRef
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    Neurology and Therapy.2025; 14(4): 1157.     CrossRef
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    Diabetes Research and Clinical Practice.2025; 224: 112175.     CrossRef
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    Jinming Tan, Yingying Li, Zhibing Zhang, Xiaoxi Li
    Food Research International.2025; 217: 116839.     CrossRef
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    Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi
    Diabetes & Metabolism Journal.2025; 49(3): 333.     CrossRef
  • Fibroblast Growth Factor 21 Levels Are Associated With Perception and Neural Responses to Sweetness in Type 2 Diabetes Mellitus
    Piao Kang, Ying Zhang, Dian Zeng, Dan Liu, Rui Han, Yuwei Lu, Di Cheng, Qinyi Wang, Silin Liu, Liang Wu, Qian Wu, Shujie Yu, Anran Chen, Jingyi Guo, Wenli Ge, Jiacheng Ni, Jingyi Yang, Xiaomeng Wu, Lifei Ma, Weiping Jia, Qichen Fang, Yuehua Li, Huating Li
    Diabetes & Metabolism Journal.2025; 49(4): 893.     CrossRef
  • Glucagon-like peptide-1 medicines in neurological and psychiatric disorders
    Susanna Fang, Fiona Cui, Daniel J. Drucker
    Cell Reports Medicine.2025; 6(12): 102511.     CrossRef
  • The Potential Effects of Exercise Training on Cortical Glutamatergic Synapse, Retrograde Endocannabinoid Signaling, and the Oxytocin Signaling Pathway in the Diabetic–Obesity Cortex: An In Silico Study
    Yin-Yu Chiang, Michael Anekson Widjaya, Shin-Da Lee
    International Journal of Molecular Sciences.2025; 27(1): 266.     CrossRef
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    Jae Hyun Bae
    Diabetes & Metabolism Journal.2024; 48(1): 157.     CrossRef
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    Kyu Sik Kim, Joon Seok Park, Eunsang Hwang, Min Jung Park, Hwa Yun Shin, Young Hee Lee, Kyung Min Kim, Laurent Gautron, Elizabeth Godschall, Bryan Portillo, Kyle Grose, Sang-Ho Jung, So Lin Baek, Young Hyun Yun, Doyeon Lee, Eunseong Kim, Jason Ajwani, Seo
    Science.2024; 385(6707): 438.     CrossRef
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    Physiology & Behavior.2024; 283: 114622.     CrossRef
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    Ryan J Jalleh, Mark P Plummer, Chinmay S Marathe, Mahesh M Umapathysivam, Daniel R Quast, Christopher K Rayner, Karen L Jones, Tongzhi Wu, Michael Horowitz, Michael A Nauck
    The Journal of Clinical Endocrinology & Metabolism.2024; 110(1): 1.     CrossRef
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    Ryan J Jalleh, Chinmay S Marathe, Christopher K Rayner, Karen L Jones, Mahesh M Umapathysivam, Tongzhi Wu, Daniel R Quast, Mark P Plummer, Michael A Nauck, Michael Horowitz
    Endocrinology.2024;[Epub]     CrossRef
  • Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial
    Natalia McInnes, Stephanie Hall, Heather A. Lochnan, Stewart B. Harris, Zubin Punthakee, Ronald J. Sigal, Irene Hramiak, Mohammed Azharuddin, Joanne F. Liutkus, Jean‐François Yale, Farah Sultan, Ada Smith, Rose E. Otto, Diana Sherifali, Yan Yun Liu, Hertz
    Diabetes, Obesity and Metabolism.2023; 25(11): 3347.     CrossRef
  • Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy
    Hussein Zaitoon, Ronit Lubetzky, Achiya Z. Amir, Hadar Moran-Lev, Liora Sagi, Michal Yacobi-Bach, Ophir Borger, Efrat Chorna, Yael Lebenthal, Avivit Brener
    Acta Diabetologica.2023; 60(8): 1099.     CrossRef
  • What can functional brain imaging teach us about remission of type 2 diabetes?
    Dhruti Hirani, Shahd Alabdulkader, Alexander. D. Miras, Victoria Salem
    Diabetic Medicine.2023;[Epub]     CrossRef
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    Nikolaos Perakakis, Olivia M. Farr, Christos S. Mantzoros
    Diabetes, Obesity and Metabolism.2021; 23(5): 1202.     CrossRef
  • Aberrant Brain Functional Connectivity Strength and Effective Connectivity in Patients with Type 2 Diabetes Mellitus
    Xi Guo, Su Wang, Yu-Chen Chen, Heng-Le Wei, Gang-Ping Zhou, Yu-Sheng Yu, Xindao Yin, Kun Wang, Hong Zhang, Eusebio Chiefari
    Journal of Diabetes Research.2021; 2021: 1.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal
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