A COMPREHENSIVE ANALYSIS OF TYPE 3 DIABETES: CONNECTING METABOLIC DYSFUNCTION WITH ALZHEIMER'S DISEASE
Main Article Content
Keywords
Keywords Diabetes mellitus, Alzheimer disease, Insulin resistance, Nerve degeneration, Glucose metabolism disorders, Oxidative stress, Transcriptome.
Abstract
Background-Insulin resistance, which affects neural transmission and energy metabolism, is one metabolic abnormality that is increasingly linked to Alzheimer's disease (AD). Amyloid-beta buildup, tau pathology, and neuroinflammation are all exacerbated by disruption of the insulin pathways in the brain. The idea of "Type 3 Diabetes" (T3D) was born because of these common characteristics. The purpose of this study is to examine the molecular connections between AD and insulin resistance and to highlight new treatment approaches.
Method- Using PubMed, Scopus, Web of Science, and the Cochrane Library, a systematic review was carried out in compliance with PRISMA standards to find publications that were published between January 2010 and July 2025. "Diabetes Mellitus," "Insulin Resistance," "Alzheimer Disease," "Nerve Degeneration," "Cognitive Dysfunction," and other relevant clinical and biological keywords were among the search terms used. The final analysis contained 213 peer-reviewed articles after duplicates were eliminated and predetermined inclusion and exclusion criteria were applied.
Results- A major pathogenic factor that has been repeatedly found to affect tau phosphorylation, amyloid-beta clearance, and brain glucose uptake is insulin resistance. Insulin signaling pathway disruption, particularly PI3K/Akt and GLUT4 translocation, has been linked to oxidative stress, neuroinflammation, and cognitive impairment. Transcriptomic evidence also demonstrated how non-coding RNA’s, such as MEG3 and MALAT1, regulate insulin sensitivity and glucose homeostasis, connecting metabolic imbalance to neural dysfunction.
Conclusion-The idea of T3D is supported by the fact that insulin resistance and impaired glucose metabolism are key factors in the onset and progression of AD. There is encouraging neuroprotective potential when these pathways are targeted. Validating these therapies in extensive clinical trials should be the main goal of future research.
References
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14. Zheng Y, Ma Q, Qi X, Zhu Z, Wu B. Prevalence and incidence of mild cognitive impairment in adults with diabetes in the united States. Diabetes Res Clin Pract. 2023;205:110976.
15. Mayeda ER, Haan MN, Kanaya AM, Yaffe K, Neuhaus J. Type 2 diabetes and 10-year risk of dementia and cognitive impairment among older Mexican Americans. Diabetes Care. 2013;36(9):2600–6.
16. Salinas RM, Hiriart M, Acosta I, Sosa AL, Prince MJ. Type 2 diabetes mellitus as a risk factor for dementia in a Mexican population. J Diabetes Complicat. 2016;30(7):1234–9.
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22. Harris K, Gong J, Shah M, Hajat S, Xu Y, Carcel C et al. Ethnic differences in risk factors for cognitive decline and dementia, in individuals with diabetes: Results from the advance trial. J Hypertens. 2023;41(Suppl 3).
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25. Albaik M, Sheikh Saleh D, Kauther D, Mohammed H, Alfarra S, Alghamdi A et al. Bridging the gap: glucose transporters, Alzheimer’s, and future therapeutic prospects. Front Cell Dev Biology. 2024;12.
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27. Jitendra Joshi N, Raja Sekhar Reddy A. Navigating the GSK-3β inhibitors as versatile multi-target drug ligands in Alzheimer’s disease intervention – A comprehensive review. Results Chem. 2024;7:101500.
28. Dash UC, Bhol NK, Swain SK, Samal RR, Nayak PK, Raina V et al. Oxidative stress and inflammation in the pathogenesis of neurological disorders: mechanisms and implications. Acta Pharm Sinica B. 2024;15(1).
29. Marttinen M, Takalo M, Natunen T, Wittrahm R, Gabbouj S, Kemppainen S et al. Molecular mechanisms of synaptotoxicity and neuroinflammation in Alzheimer’s disease. Front NeuroSci. 2018;12.
30. Trigo D, Avelar C, Fernandes M, Sá J. Da Cruz e Silva O. Mitochondria, energy, and metabolism in neuronal health and disease. FEBS Lett. 2022;596(9):1095–110.
31. Zhang W, Xiao D, Mao Q, Xia H. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Therapy. 2023;8(1):267.
32. Green JL, Dos Santos WF, Fontana ACK. Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: opportunities for novel therapeutics development. Biochem Pharmacol. 2021;193:114786.
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Sep 30, 2025
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Komal Yadav, Dr. Pragnesh Patani, Mr Rahul Kannar, & Dr. Nishkruti R. Mehta. (2025). A COMPREHENSIVE ANALYSIS OF TYPE 3 DIABETES: CONNECTING METABOLIC DYSFUNCTION WITH ALZHEIMER’S DISEASE. Journal of Population Therapeutics and Clinical Pharmacology, 32(8), 1178-1191. https://doi.org/10.53555/1mp6cs91
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Author Biographies
Komal Yadav
Student, Khyati College of Pharmacy, Palodiya, Ahmedabad
Dr. Pragnesh Patani
Principal, Khyati College of Pharmacy, Palodiya, Ahmedabad
Mr Rahul Kannar
Assistant Professor, Department of Pharmacology, Khyati College of Pharmacy, Palodia, Ahmedabad
Dr. Nishkruti R. Mehta
Professor & Head, Department of Pharmacology, Khyati College of Pharmacy, Palodiya , Ahmedabad
How to Cite
Komal Yadav, Dr. Pragnesh Patani, Mr Rahul Kannar, & Dr. Nishkruti R. Mehta. (2025). A COMPREHENSIVE ANALYSIS OF TYPE 3 DIABETES: CONNECTING METABOLIC DYSFUNCTION WITH ALZHEIMER’S DISEASE. Journal of Population Therapeutics and Clinical Pharmacology, 32(8), 1178-1191. https://doi.org/10.53555/1mp6cs91