Type 2 Diabetes Mellitus and Alzheimer Disease: A Review of the Potential Links

2021 ◽  
Vol 18 ◽  
Author(s):  
Majid Pakdin ◽  
Samaneh Toutounchian ◽  
Sina Namazi ◽  
Zahra Arabpour ◽  
Amirreza Pouladi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Impaired Glucose Metabolism ◽  
Biological Mechanisms ◽  
Environmental Association ◽  
Energy Consuming ◽  
The Brain ◽  
Aβ Production

: Diabetes mellitus and Alzheimer’s disease are considered the most prevalent diseases in older ages worldwide. The main pathology of Alzheimer’s disease is highly related with accumulation of misfolded proteins that lead to neuronal dysfunction in the brain. On the other hand, diabetes mellitus is associated with alteration of insulin signaling, which could cause the reduction of glu-cose uptake, metabolic prohibition of energy consuming cells, as well as suppression of glucose to fat conversion in the liver. In spite of having seemingly different pathological features, both dis-eases share common underlying biological mechanisms. Besides, the epidemiological and envi-ronmental links between these two diseases should not be overlooked. In this study, we aim to review shared pathological mechanisms of Alzheimer’s disease and diabetes mellitus, including impaired glucose metabolism, increased Amyloid-Beta (Aβ) production, impaired lipid metabo-lism, mitochondrial dysfunction, increased inflammation and elevated oxidative stress. Further-more, we discuss epidemiological/environmental association between these two diseases and also review animal investigations, which have evaluated the potential links between the two diseases.

scholarly journals Shared Blood Transcriptomic Signatures between Alzheimer’s Disease and Diabetes Mellitus

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 34
Author(s):  
Taesic Lee ◽  
Hyunju Lee
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Expression Patterns ◽  
Protein Protein Interactions ◽  
Hub Genes ◽  
Gene Modules ◽  
Gene Regulatory ◽  
The Brain

Alzheimer’s disease (AD) and diabetes mellitus (DM) are known to have a shared molecular mechanism. We aimed to identify shared blood transcriptomic signatures between AD and DM. Blood expression datasets for each disease were combined and a co-expression network was used to construct modules consisting of genes with similar expression patterns. For each module, a gene regulatory network based on gene expression and protein-protein interactions was established to identify hub genes. We selected one module, where COPS4, PSMA6, GTF2B, GTF2F2, and SSB were identified as dysregulated transcription factors that were common between AD and DM. These five genes were also differentially co-expressed in disease-related tissues, such as the brain in AD and the pancreas in DM. Our study identified gene modules that were dysregulated in both AD and DM blood samples, which may contribute to reveal common pathophysiology between two diseases.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

scholarly journals Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

2018 ◽  
Vol 19 (11) ◽  
pp. 3306 ◽  
Author(s):  
Andrea Tumminia ◽  
Federica Vinciguerra ◽  
Miriam Parisi ◽  
Lucia Frittitta
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Cell Activation ◽  
Insulin Signalling ◽  
Amyloid Β ◽  
Neuronal Stem Cell

In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer’s disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.

scholarly journals Association of Diabetes Mellitus Type 2 and Alzheimer's Disease

2019 ◽  
Vol 4 (4) ◽  
pp. 86-89
Author(s):  
Sasan Andalib ◽  
◽  
Amirreza Ghayeghran ◽  
Yaser Moadabi ◽  
Kamran Asadi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type

scholarly journals Title: Biochemical linkage of type 2 diabetes mellitus and Alzheimer’s disease

2019 ◽  
Vol 0 (0) ◽  
pp. 1-14
Author(s):  
samar mahmoud ◽  
Dina Abo-El-Matty ◽  
Noha Mesbah ◽  
Eman Mehanna ◽  
Mohamed Hafez
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus

scholarly journals Depression as a Risk Factor for Dementia and Alzheimer’s Disease

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 457 ◽  
Author(s):  
Vanesa Cantón-Habas ◽  
Manuel Rich-Ruiz ◽  
Manuel Romero-Saldaña ◽  
Maria del Pilar Carrera-González
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Odds Ratio ◽  
Case Control Study ◽  
Case Control ◽  
Global Deterioration Scale ◽  
Definition Of ◽  
Control Study

Preventing the onset of dementia and Alzheimer’s disease (AD), improving the diagnosis, and slowing the progression of these diseases remain a challenge. The aim of this study was to elucidate the association between depression and dementia/AD and to identify possible relationships between these diseases and different sociodemographic and clinical features. In this regard, a case-control study was conducted in Spain in 2018–2019. The definition of a case was: A person ≥ 65 years old with dementia and/or AD and a score of 5–7 on the Global Deterioration Scale (GDS). The sample consisted of 125 controls; among the cases, 96 had dementia and 74 had AD. The predictor variables were depression, dyslipidemia, type 2 diabetes mellitus, and hypertension. The results showed that depression, diabetes mellitus, and older age were associated with an increased likelihood of developing AD, with an Odds Ratio (OR) of 12.9 (95% confidence interval (CI): 4.3–39.9), 2.8 (95% CI: 1.1–7.1) and 1.15 (95% CI: 1.1–1.2), respectively. Those subjects with treated dyslipidemia were less likely to develop AD (OR 0.47, 95% CI: 0.22–1.1). Therefore, depression and diabetes mellitus increase the risk of dementia, whereas treated dyslipidemia has been shown to reduce this risk.

scholarly journals Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanan Sun ◽  
Cao Ma ◽  
Hui Sun ◽  
Huan Wang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Impaired Insulin ◽  
The Brain

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

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