From Insulin Resistance to Neurodegeneration: Exploring the Link Between Type 2 Diabetes and Alzheimer’s Disease as Type 3 Diabetes

Introduction: Alzheimer's Disease (AD) is a neurodegenerative disease that leads to a gradual decline in cognitive function. Recent evidence shows a strong cross-relationship between insulin resistance in patients of Type 2 Diabetes Mellitus and Alzheimer's Disease pathology, sharing a common link pathway that gives rise to a new concept, so-called “Type 3 Diabetes”. This review discusses the pathophysiological interrelation between Type 2 Diabetes Mellitus (T2DM) and Alzheimer's Disease (AD), focusing on common metabolic abnormalities, diagnostic biomarkers, and their therapeutic potentials. Methods: A narrative review of literature was performed based onby testing with PubMed, Scopus, and Web of Science. The search terms in the electronic database were “Alzheimer’s Disease”, “Type-3 Diabetes”, “insulin resistance”, “cognitive decline” and “neurodegeneration”. Articles were screened with relevance, quality, and contribution to the comprehension of the T2DM–AD link in mind. No meta-analysis, statistical or quantitative, was done as the data were thematically synthesized. Results: The literature consistently supports a link between Type 2 Diabetes Mellitus (T2DM) and increased Alzheimer's Disease (AD) risk. Insulin resistance disrupts neuronal signaling, glucose uptake, and promotes amyloid-beta accumulation and tau phosphorylation. Cerebrospinal fluid biomarkers and PET imaging provide diagnostic insights. Pharmacologic agents like GLP- 1 receptor agonists show neuroprotective potential. Discussion: The relationship between Type 2 Diabetes Mellitus (T2DM) and the risk of Alzheimer's Disease (AD) is consistently reported in the literature. It dysregulates neuronal signaling, glucose uptake, and increases amyloid-beta and tau phosphorylation. Diagnostic findings are based on cerebrospinal fluid biomarkers and PET imaging. Pharmacological agents such as GLP-1 receptor agonists hold promise as neuroprotective agents. Conclusion: Viewing Alzheimer's Disease (AD) in the context of metabolic failure may fundamentally change the way to prevent, diagnose, and treat the disease. Considering a “Type 3 Diabetes” provides a paradigm shift in awareness of the insulin–brain connection and underscores the necessity of a focused, combined therapeutic approach.