Diabetes and Alzheimer’s disease

Diabetes and AD may share risk factors, including overlapping metabolic risk factors. Apolipoprotein E (APOE) also regulates lipid metabolism.⁹ This suggests that the aetiology of AD includes metabolic risk factors, which are also involved in the development of diabetes.¹⁰ Hyperglycaemia is the main characteristic of impaired glucose tolerance and diabetes,¹¹with evidence that hyperglycaemia is a potential risk factor for the development of cognitive dysfunction and dementia.¹²

An additional type of diabetes that has recently been identified – type 3 diabetes mellitus (T3DM) – manifests as insulin resistance within the brain.¹³ As a result, T3DM may impact neurocognition and contribute to the aetiology of AD.¹³ Scientists have attempted to define T3DM as a metabolic syndrome that may lead to abnormalities associated with progressive brain insulin resistance, accumulation of neurotoxins, and neuronal stress; resulting in neurodegeneration.¹⁴ Insulin resistance is now a well-known essential feature of T3DM; therefore, treatments for T3DM, such as those aimed at improving insulin sensitivity, may also be beneficial for patients at risk for AD at the early stages.¹³Once dementia is diagnosed and pathological changes are evident, it is difficult to reverse the progression of disease.¹¹ Therefore, an important goal for diabetes-related dementia is to identify individual risk factors and prevent the occurrence of diabetes and dementia.¹¹

References:
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3.Tomic D, Shaw JE, Magliano DJ. The burden and risks of emerging complications of diabetes mellitus. Nat Rev Endocrinol 2022; 18 (9): 525–539.

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6.Pearson-Stuttard J, Bennett J, Cheng YJ, et al. Trends in predominant causes of death in individuals with and without diabetes in England from 2001 to 2018: an epidemiological analysis of linked primary care records. Lancet Diabetes Endocrinol 2021; 9 (3): 165–173.

7.Gregg EW, Cheng YJ, Srinivasan M, et al. Trends in cause-specific mortality among adults with and without diagnosed diabetes in the USA: an epidemiological analysis of linked national survey and vital statistics data. Lancet 2018; 391 (10138): 2430–2440.

8.Chatterjee S, Mudher A. Alzheimer’s disease and type 2 diabetes: a critical assessment of the shared pathological traits. Front Neurosci 2018; 12: 383.

9.Carmel JF, Tarnus E, Cohn JS, et al. High expression of apolipoprotein E impairs lipid storage and promotes cell proliferation in human adipocytes. J Cell Biochem 2009; 106 (4): 608–617.

10.Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J 2012; 42 (5): 484–491.

11.Lee HJ, Seo HI, Cha HY, et al. Diabetes and Alzheimer’s disease: mechanisms and nutritional aspects. Clin Nutr Res 2018; 7 (4): 229–240.

12.Barbagallo M, Dominguez LJ. Type 2 diabetes mellitus and Alzheimer’s disease. World J Diabetes 2014; 5 (6): 889–893.