Altered Amyloid-β and Tau Proteins in Neural-Derived Plasma Exosomes in Patients with Type 2 Diabetes and Orthostatic Hypotension

Abstract BackgroundEmerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer disease (AD). The aim of the study was to investigate whether neural-derived plasma exosomal amyloid-β and tau protein levels are associated with OH in diabetes mellitus (DM) patients.MethodsThere were 274 subjects without dementia included in the study: 81 control participants (controls), 101 normotensive patients with DM without OH, and 92 patients with DM and neurogenic OH (DMOH). Neuronal-derived exosomal proteins were measured by ELISA kits for amyloid-β and tau.ResultsThe neuronal-derived exosome levels of Aβ42, T-tau, and P-T181-tau in the DM with OH group were higher than those in the DM and control groups. Multivariable linear regression analysis showed that the presence of OH in patients with DM was associated with elevated exosomal Aβ42 (β = 0.172, P = 0.018), T-tau(β = 0.159, P = 0.030), and P-T181-tau (β = 0.220, P = 0.003) levels after adjustment for age, sex, APOE ε4, duration of type 2 diabetes, HbA1c and cardiovascular risk factors. Furthermore, the levels of Aβ42, T-tau, and P-T181-tau in neuronal-derived exosomes were correlated with HIF-1α levels and the drop in mean cerebral blood flow velocity from the supine to upright position.ConclusionsThe presence of OH in DM patients was independently associated with elevated the Aβ42, T-tau, and PT181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.Trial registrationChinese Clinical Trial Registry (Identifier: ChiCTR1900021544 ). Registered 27 February 2019.

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Altered Amyloid-β and Tau Proteins in Neural-Derived Plasma Exosomes of Type 2 Diabetes Patients with Orthostatic Hypotension

Journal of Alzheimer s Disease ◽

10.3233/jad-210216 ◽

2021 ◽

pp. 1-12

Author(s):

Jinbiao Zhang ◽

Haiyan Chi ◽

Tong Wang ◽

Shukun Zhang ◽

Tengqun Shen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Orthostatic Hypotension ◽

Cerebral Blood Flow Velocity ◽

Linear Regression Analysis ◽

Amyloid Β ◽

Tau Proteins ◽

Cerebral Hypoperfusion ◽

Multivariable Linear Regression Analysis ◽

T Tau

Background: Emerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer’s disease (AD). The exosomes in the blood can reflect the pathological changes in the brain. Objective: o investigate whether neural-derived plasma pathogenic proteins of AD levels are associated with OH in diabetes mellitus (DM) patients. Methods: There were 274 subjects without dementia included in the study: 81 control participants (controls), 101 normotensive patients with DM without OH, and 92 patients with DM and neurogenic OH (DMOH). Neural-derived exosomal proteins were measured by ELISA kits for amyloid-β (Aβ) and tau. Results: The neural-derived exosome levels of Aβ 42, total tau (T-tau), and tau phosphorylated at threonine 181 (P-T181-tau) in the DM with OH group were higher than those in the DM and control groups. Multivariable linear regression analysis showed that the presence of OH in patients with DM was associated with elevated exosomal Aβ42 (β= 0.172, p = 0.018), T-tau (β= 0.159, p = 0.030), and P-T181-tau (β= 0.220, p = 0.003) levels after adjustment for age, sex, APOE ɛ4, duration of type 2 diabetes, HbA1c, and cardiovascular risk factors. Furthermore, the levels of Aβ 42, T-tau, and P-T181-tau in neural-derived exosomes were correlated with HIF-1α levels and the drop in mean cerebral blood flow velocity from the supine to upright position. Conclusion: The presence of OH in DM patients was independently associated with elevated the Aβ 42, T-tau, and P-T181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.

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The Link between Type 2 Diabetes and Neurodegeneration: Roles for Amyloid-β, Amylin, and Tau Proteins

Journal of Alzheimer s Disease ◽

10.3233/jad-161192 ◽

2017 ◽

Vol 59 (2) ◽

pp. 421-432 ◽

Cited By ~ 79

Author(s):

Prashant Bharadwaj ◽

Nadeeja Wijesekara ◽

Milindu Liyanapathirana ◽

Philip Newsholme ◽

Lars Ittner ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amyloid Β ◽

Tau Proteins

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Association of Plasma Myeloperoxidase Level with Risk of Coronary Artery Disease in Patients with Type 2 Diabetes

Disease Markers ◽

10.1155/2015/761939 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 8

Author(s):

Ping Song ◽

Jin Xu ◽

Yongfeng Song ◽

Shiliang Jiang ◽

Haitao Yuan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Logistic Analysis ◽

Artery Disease

Aims. This study aimed to investigate whether the change of plasma myeloperoxidase (MPO) level would be associated with the incidence of coronary artery disease (CAD) among diabetic patients.Methods. 339 patients with type 2 diabetes mellitus (DM) underwent coronary angiography. Of them, 204 cases had CAD and were assigned to CAD group and 135 cases without CAD were assigned to non-CAD group.Results. Compared to non-CAD group, CAD group had higher level of plasma MPO (p<0.01). Multiple linear regression analysis showed that plasma MPO level was correlated with Gensini score. Multiple logistic analysis showed that the odds ratios for CAD across increasing tertiles of MPO level were 1.191 (0.971–1.547) and 1.488 (1.115–2.228) (p=0.048,p=0.009versus 1st tertile of MPO level, resp.) by adjusting for age, sex, and other conventional risk factors for CAD. The subjects were stratified into nine groups according to tertiles of MPO and HbA1c. The odds ratio for CAD was significantly higher in group with highest levels of MPO and HbA1c (OR = 4.08,p<0.01).Conclusion. Plasma MPO level was positively correlated with the degree of coronary artery stenosis in type 2 diabetic patients, and increasing blood glucose might amplify the association between MPO and CAD.

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Comprehensive Review on Neuro-Degenerative Type 3DM

Current Diabetes Reviews ◽

10.2174/1573399818666211213103624 ◽

2021 ◽

Vol 18 ◽

Author(s):

Chandani V. Chandarana ◽

Salona Roy

Keyword(s):

Type 2 Diabetes ◽

Insulin Signaling ◽

Insulin Signalling ◽

Amyloid Β ◽

Diabetes Mellitus Type 1 ◽

Current Data ◽

The Body ◽

Type I ◽

Therapeutic Benefits

: Alzheimer disease (AD) is thought to be the metabolic illness raised by defective insulin signaling, insulin resistance, and low insulin levels in the brain, according to a growing body of research. The "Type 3 diabetes" has been postulated for AD because reduced insulin signalling has molecular and physiological consequences that are comparable to Type I and Type 2 diabetes mellitus (Type 1 DM and Type 2 DM, respectively). The similarities between type 2 diabetes and Alzheimer's disease suggest that these clinical trials might yield therapeutic benefits. However, it's important to note that lowering your risk of Alzheimer's dementia, whether you have diabetes or not, is still a multidimensional process involving factors like exercise, smoking, alcohol, food, and mental challenge. The current aim is to show the relationship between T3D and AD being based on both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are the result of an impaired insulin signaling. The brain's metabolism with its high lipid content and energy needs, places excess demands on mitochondria and appears more susceptible to oxidative damage than the rest of the body. Current data suggests that increased oxidative stress relates to amyloid-β (Aβ) pathology and onset of AD.

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Effect of Type 2 Diabetes Mellitus and diabetic medication on Pulmonary Function

Current Respiratory Medicine Reviews ◽

10.2174/1573398x17666210121141412 ◽

2021 ◽

Vol 17 ◽

Author(s):

Alaa M. Hammad ◽

Waleed Qirim ◽

Ameen Alassi ◽

Dana Hyassat

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Pulmonary Function ◽

Disease Duration ◽

Linear Regression Analysis ◽

Forced Expiratory Volume ◽

Control Group

Background: Type 2 diabetes mellitus (T2DM) is a chronic condition with an impairing effect on multiple organs. Numerous respiratory disorders have been observed in patients with T2DM. However, T2DM e ect on pulmonary function is ff inconclusive. Aims: In this study, we investigated the effect of T2DM on respiratory function and the correlation of glycemic control, diabetes duration and insulin intake. Methods: 1500 patients were recruited for this study, 560 having T2DM for at least a year were included in the final data, in addition to 540 healthy volunteers. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% (FEF 25-75%), as well as FEV1/FVC ratio values were measured. Results: A two-sample t-test showed that z-scores produced by Al-Qerem et al.’s equations for FEV1, FVC, and FEF 25-75% were significantly lower for the T2DM group than the control group (p < 0.01). FEV1/FVC ratio in T2DM group were significantly higher (p < 0.01). Multiple linear regression analysis found that glycemic control represented by HbA1c as well as disease duration were negatively associated with pulmonary function (p < 0.01). However, insulin intake was found to have no significant correlation with the pulmonary function. Conclusion: T2DM was linked to reduced pulmonary function and was consistent with a restrictive ventilation pattern. HbA1c as well as disease duration were independent risk factors for reduced pulmonary function.

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

International Journal of Molecular Sciences ◽

10.3390/ijms19113306 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3306 ◽

Cited By ~ 39

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.

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Predictors of Diabetes Self-Management Behaviors in Type 2 Diabetes Patients

Iranian journal of diabetes and obesity ◽

10.18502/ijdo.v12i4.5180 ◽

2021 ◽

Author(s):

Golnaz Azami ◽

Soh Kim Lam ◽

Sazlina Shariff-Ghazali ◽

Salmiah Mohd Said ◽

Sanaz Aazami ◽

...

Keyword(s):

Quality Of Life ◽

Type 2 Diabetes ◽

Linear Regression Analysis ◽

Self Management ◽

P Value ◽

Efficacy Expectation ◽

The Mean ◽

Management Behaviors

Objective: Type 2 diabetes mellitus (T2DM) is a chronic condition that requires consistent medical care to help control glycemic indices. Diabetes self-management is found to be essential for optimal glycemic control. This study aimed to investigate the predictors of diabetes self-management in adult with T2DM. Materials and Methods: A cross-sectional study was conducted. A purposive sample of 142 adults with T2DM attended an outpatient endocrine clinic in an academic hospital in Ilam, Iran was invited to participate in this study from September to October 2016. The data were collected using a combination of validated questionnaires and the blood sample. IBM SPSS software version 22 used to conduct the analysis. Hierarchical linear regression analysis with the stepwise method was used to explore the predictors of diabetes self-management. Results: The mean age of participants was 54.2 ± (11.8) years. The mean duration of diabetes was 8.9 ± (7.4). Hierarchical linear regression analysis determined that self-management behaviors had positive relationship with efficacy expectation (B= 0.445, P-value< 0.01), quality of life (B= 0.222, P-value= 0.02), and has a negative relationship with HbA1c (B= -0.194, P-value= 0.01). Conclusion: The result of our study indicate that better diabetes self-management behaviors can be predicted by higher efficacy expectation, the better quality of life and lower HbA1c levels. Future interventions should focus on enhancing efficacy expectation, quality of life and optimizing glycemic control to improve self-management of diabetes.

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Case 24: Orthostatic Cerebral Hypoperfusion Syndrome with Vision Loss

Autonomic Testing ◽

10.1093/med/9780190889227.003.0029 ◽

2019 ◽

pp. 157-162

Author(s):

Peter Novak

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Orthostatic Hypotension ◽

Flow Velocity ◽

Blood Flow Velocity ◽

Vision Loss ◽

Cerebral Blood Flow Velocity ◽

Cerebral Hypoperfusion ◽

Tilt Test

The tilt test showed orthostatic cerebral hypoperfusion syndrome (OCHOS) with intermittent reduction in cerebral blood flow velocity and vision loss. OCHOS is associated with reduced orthostatic cerebral blood flow velocity without orthostatic hypotension or arrhythmia.

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Case 23: Orthostatic Cerebral Hypoperfusion Syndrome, Severe

Autonomic Testing ◽

10.1093/med/9780190889227.003.0028 ◽

2019 ◽

pp. 153-156

Author(s):

Peter Novak

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Orthostatic Hypotension ◽

Flow Velocity ◽

Blood Flow Velocity ◽

Cerebral Blood Flow Velocity ◽

Cerebral Hypoperfusion ◽

Tilt Test

The tilt test showed severe orthostatic cerebral hypoperfusion syndrome (OCHOS) with reduced cerebral blood flow velocity. OCHOS is associated with reduced orthostatic cerebral blood flow velocity without orthostatic hypotension or arrhythmia.

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