Considering Alzheimer's Disease as a Type 3 Diabetes

A number of researchers have pointed out similarities between some of the risk factors and mechanisms of type 2 diabetes and Alzheimer's disease, a few even going so far as to suggest that Alzheimer's should be classified as type 3 diabetes:

Type 2 diabetes mellitus (T2DM) is currently extremely common due to the prevalence of obesity, as well as the aging of the population. Prevention and treatment strategies for the classical macrovascular and microvascular complications of diabetes mellitus have significantly improved. Therefore, people are living longer with diabetes mellitus, which might lead to the emergence of new complications. Dementia is one example of these emerging new complications. Compared with the general population, the increased risk of dementia is 50%-150% in people with T2DM.

Over the past three decades, numerous epidemiological studies have shown a clear association between T2DM and an increased risk of developing AD. In addition, T2DM-related conditions, including obesity, hyperinsulinemia, and metabolic syndrome, may also be risk factors for AD. The exact mechanisms with clinical relevance are unclear. Several mechanisms have been proposed, including insulin resistance and deficiency, impaired insulin receptor and impaired insulin growth factor (IGF) signaling, glucose toxicity, problems due to advanced glycation end products and their receptors, cerebrovascular injury, vascular inflammation, and others.

In this review, we discuss insulin resistance and deficiency. Studies have shown that insulin resistance and deficiency can interact with amyloid-β protein and tau protein phosphorylation, each leading to the onset and development of AD. Based on those epidemiological data and basic research, it was recently proposed that AD can be considered as "type 3 diabetes". Special attention has been paid to determining whether antidiabetic agents might be effective in treating AD. There has been much research both experimental and clinical on this topic. Although the results of these trials seem to be contradictory, this approach is also full of promise.



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