Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline

Chapple, Brooke; Bayliss, Emily; Woodfin, Seth; Smith, Merritt; Winter, Jeremiah; Moore, William

doi:10.3390/diseases13110359

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Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline

by

Brooke Chapple

¹,

Emily Bayliss

¹

,

Seth Woodfin

²,

Merritt Smith

¹,

Jeremiah Winter

¹ and

William Moore

^1,*

¹

Department of Biology and Chemistry, School of Health Sciences, Liberty University, Lynchburg, VA 24515, USA

²

Department of Biomedical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, WV 24901, USA

^*

Author to whom correspondence should be addressed.

Diseases 2025, 13(11), 359; https://doi.org/10.3390/diseases13110359

Submission received: 28 July 2025 / Revised: 22 October 2025 / Accepted: 4 November 2025 / Published: 5 November 2025

(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)

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Abstract

Type 3 diabetes (T3D) is characterized by chronic insulin resistance and insulin deficiency in the brain, leading to neuronal death, inflammation, oxidative stress, apoptosis, and synaptic dysfunction. These pathological processes contribute to cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. However, despite increasing evidence that links insulin resistance to cognitive impairment, the precise mechanisms that underly T3D remain largely unknown. This highlights a critical gap in research and potential therapeutic strategies. Given the significant impact of diet on metabolic health, investigating the correlation between the gut–brain axis may offer novel insights into the prevention and management of T3D. This review aims to elucidate the potential connections between insulin resistance and cognitive decline while also proposing interventions to slow aging and reduce the risk of early cognitive decline. At the same time, we acknowledge that the classification of type 3 diabetes is debatable and there is uncertainty as to whether insulin resistance is a primary driver or secondary manifestation of neurodegeneration.

Keywords: Type 3 diabetes; insulin resistance; cognitive decline; Alzheimer’s disease; neurodegeneration; gut–brain axis; oxidative stress; neuroinflammation; synaptic dysfunction; metabolic health

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MDPI and ACS Style

Chapple, B.; Bayliss, E.; Woodfin, S.; Smith, M.; Winter, J.; Moore, W. Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline. Diseases 2025, 13, 359. https://doi.org/10.3390/diseases13110359

AMA Style

Chapple B, Bayliss E, Woodfin S, Smith M, Winter J, Moore W. Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline. Diseases. 2025; 13(11):359. https://doi.org/10.3390/diseases13110359

Chicago/Turabian Style

Chapple, Brooke, Emily Bayliss, Seth Woodfin, Merritt Smith, Jeremiah Winter, and William Moore. 2025. "Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline" Diseases 13, no. 11: 359. https://doi.org/10.3390/diseases13110359

APA Style

Chapple, B., Bayliss, E., Woodfin, S., Smith, M., Winter, J., & Moore, W. (2025). Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline. Diseases, 13(11), 359. https://doi.org/10.3390/diseases13110359

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Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline

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