Brooke Chapple, Emily Bayliss, Seth Woodfin, Marilyn Smith, Jeremiah Winter, William T. Moore
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.