Connection between Type 2 Diabetes and Alzheimer\'s disease: Insights from epidemiology to mechanisms and treatment approaches

• Author Details:   
• Meena Rathore
• Mudit Sharma
• Anand Singh Chouhan ^*

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This paper aspires to present an extensive exploration of the epidemiological data that connects Type 2 Diabetes Mellitus (T2DM) and its associated ailments, including obesity, hyperinsulinemia, and metabolic syndrome, to the onset of Alzheimer’s disease (AD). Objective is to delve into the intricate workings, especially the nuances of insulin resistance and deficiency, that might illuminate the relationship linking T2DM and AD, and to evaluate the promise of anti-diabetic medications in the therapeutic landscape of AD. A comprehensive exploration was conducted to examine the research on the relationship between insulin resistance and deficiency with amyloid-β accumulation and tau protein phosphorylation, both of which are key factors in the onset and progression of Alzheimer's disease. The study focused on clinical investigations involving anti-diabetic medications such as thiazolidinediones, metformin, insulin, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors, evaluating their potential use in Alzheimer's treatment. Epidemiological and foundational studies indicate that Alzheimer's Disease (AD) may be likened to "Type 3 Diabetes." Despite the mixed outcomes from clinical trials involving anti-diabetic therapies for AD, the potential remains intriguing. The effectiveness of these drugs, importantly, hinges on whether or not the apolipoprotein E (APOE)-?4 variant is present, as individuals without the APOE-?4 allele tend to have more favourable outcomes. The intricate connection linking T2DM and AD is bolstered by both epidemiological and mechanistic insights, yet the efficacy of anti-diabetic medications for addressing AD necessitates deeper exploration, especially considering genetic elements like the APOE-?4 genotype.

Keywords: Type 2 diabetes mellitus, Alzheimer’s disease, Insulin resistance, anti-diabetic agents, APOE-?4 genotype, amyloid-β, tau protein, clinical trials.