Comprehensive Review on Neuro-Degenerative Type 3DM

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.

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.

Serum Ferritin Status of Patients with Type 2 DM Attending OPD of BIRDEM General Hospital

2020 ◽  
Vol 11 (1) ◽  
pp. 7-10
Author(s):  
Khadiza Begum ◽  
Fahmida Islam ◽  
Farjana Aktar ◽  
Murshida Aziz ◽  
Tohfa E Ayub Tahiya
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Serum Ferritin ◽  
Study Groups ◽  
Acute Phase Reactant ◽  
The Body ◽  
Iron Stores ◽  
Normal Healthy Individual ◽  
Diabetes Patients

Background: In recent times much is talked about of serum ferritin, an acute phase reactant a marker of iron stores in the body and its association with diabetes mellitus. Studies implicate that increased body iron stores and subclinical hemochromatosis has been associated with the development of glucose intolerance, type 2 diabetes and its micro as well as macrovascular complications. Material & Methods: This study was carried out to examine and to observe for any relationship between serum ferritin with Type 2 diabetes mellitus. Our study populations were included 163. Among them 81 type 2 diabetes patients as a case (M=49,F=32, mean 44.68 age in years)and 82 normal healthy individual as a control ( M=35, F=47 , mean 34.71 in years). Results: Majority were healthy outpatients who had come for regular checkup and were matched with controls. Serum ferritin and FBS were estimated and other investigations. Results showed that although Serum ferritin was in the normal range value it was increased in type 2 diabetes patients than in controls and was statistically significant, we did get a positive correlation with duration of diabetes. It can be concluded that there were positive associations between serum ferritin and FBG, age, sex among study groups. Conclusion: In conclusion our study shows that there is significant correlation between increased serum ferritin in diabetes compared to individuals with normal blood sugars in this part and hyper ferritinemia may be one of the causes for development of insulin resistance before overt diabetes. Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 7-10

scholarly journals A comprehensive evaluation of methods for Mendelian randomization using realistic simulations and an analysis of 38 biomarkers for risk of type 2 diabetes

2021 ◽  
Author(s):  
Guanghao Qi ◽  
Nilanjan Chatterjee
Keyword(s):  
Type 2 Diabetes ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Real Data ◽  
Causal Effects ◽  
Type I ◽  
Genome Wide Association Studies ◽  
Simulation Studies ◽  
Sample Sizes

Abstract Background Previous studies have often evaluated methods for Mendelian randomization (MR) analysis based on simulations that do not adequately reflect the data-generating mechanisms in genome-wide association studies (GWAS) and there are often discrepancies in the performance of MR methods in simulations and real data sets. Methods We use a simulation framework that generates data on full GWAS for two traits under a realistic model for effect-size distribution coherent with the heritability, co-heritability and polygenicity typically observed for complex traits. We further use recent data generated from GWAS of 38 biomarkers in the UK Biobank and performed down sampling to investigate trends in estimates of causal effects of these biomarkers on the risk of type 2 diabetes (T2D). Results Simulation studies show that weighted mode and MRMix are the only two methods that maintain the correct type I error rate in a diverse set of scenarios. Between the two methods, MRMix tends to be more powerful for larger GWAS whereas the opposite is true for smaller sample sizes. Among the other methods, random-effect IVW (inverse-variance weighted method), MR-Robust and MR-RAPS (robust adjust profile score) tend to perform best in maintaining a low mean-squared error when the InSIDE assumption is satisfied, but can produce large bias when InSIDE is violated. In real-data analysis, some biomarkers showed major heterogeneity in estimates of their causal effects on the risk of T2D across the different methods and estimates from many methods trended in one direction with increasing sample size with patterns similar to those observed in simulation studies. Conclusion The relative performance of different MR methods depends heavily on the sample sizes of the underlying GWAS, the proportion of valid instruments and the validity of the InSIDE assumption. Down-sampling analysis can be used in large GWAS for the possible detection of bias in the MR methods.

scholarly journals Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Repeated Measures ◽  
Medical Information ◽  
Controlled Trial ◽  
Extracellular Volume ◽  
Cardiovascular Outcomes ◽  
Fluid Volume ◽  
The Body

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

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.

Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation

2015 ◽  
Vol 129 (12) ◽  
pp. 1083-1096 ◽  
Author(s):  
Joseph B. McPhee ◽  
Jonathan D. Schertzer
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
The Body ◽  
Tissue Inflammation ◽  
Gut Barrier Function ◽  
Inflammatory Status ◽  
Obesity And Diabetes

The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

A New Model of Primary Human Adipocytes Reveals Reduced Early Insulin Signalling in Type 2 Diabetes

2004 ◽  
Vol 36 (8) ◽  
pp. 531-537 ◽  
Author(s):  
P. Algenstaedt ◽  
N. Rosenblatt ◽  
I. Kolb ◽  
A. Krützelmann ◽  
B. Schwarzloh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signalling ◽  
Human Adipocytes ◽  
New Model

Mutation of the 5' untranslated region stem-loop mRNA structure reduces type I collagen deposition and arterial stiffness in male obese mice

2021 ◽  
Author(s):  
Francisco I. Ramirez-Perez ◽  
Makenzie L. Woodford ◽  
Mariana Morales-Quinones ◽  
Zachary I. Grunewald ◽  
Francisco J Cabral-Amador ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Arterial Stiffness ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Deposition ◽  
Wild Type ◽  
Stem Loop ◽  
Arterial Stiffening

Arterial stiffening, a characteristic feature of obesity and type 2 diabetes, contributes to the development and progression of cardiovascular diseases (CVD). Currently, no effective prophylaxis or therapeutics is available to prevent or treat arterial stiffening. A better understanding of the molecular mechanisms underlying arterial stiffening is vital to identify newer targets and strategies to reduce CVD burden. A major contributor to arterial stiffening is increased collagen deposition. In the 5' untranslated regions of mRNAs encoding for type I collagen, an evolutionally conserved stem-loop (SL) structure plays an essential role in its stability and post-transcriptional regulation. Here, we show that feeding a high fat/high sucrose (HFHS) diet for 28 weeks increases adiposity, insulin resistance, and blood pressure in male wild-type littermates. Moreover, arterial stiffness, assessed in vivo via aortic pulse wave velocity, and ex vivo using atomic force microscopy in aortic explants or pressure myography in isolated femoral and mesenteric arteries, was also increased in those mice. Notably, all these indices of arterial stiffness, along with collagen type I levels in the vasculature, were reduced in HFHS-fed mice harboring a mutation in the 5'SL structure, relative to wild-type littermates. This protective vascular phenotype in 5'SL-mutant mice did not associate with a reduction in insulin resistance or blood pressure. These findings implicate the 5'SL structure as a putative therapeutic target to prevent or reverse arterial stiffening and CVD associated with obesity and type 2 diabetes.

The use of apple cider vinegar as a secondary treatment line with conventional diabetic treatment as a new medical hypothesis linking type 1 diabetes and type 2 diabetes

2021 ◽  
Vol 11 (2) ◽  
pp. 45-46
Author(s):  
Ahed J Alkhatib
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
The Body ◽  
Secondary Treatment ◽  
Therapeutic Approaches ◽  
Apple Cider ◽  
Treatment Line ◽  
Diabetic Treatment

The diabetes as a disease has been reported for 3500 years. Although diagnostic and therapeutic approaches have continuously developed, no definitive therapeutic approaches have so far been reached. Diabetes is not a single disease; it interferes with various systems in the body including nervous system and cardiovascular system. The therapeutic lines for type 1 diabetes start with insulin and will need another treatment such as metformin. On the other hand, type 2 diabetes treatment strategies start with metformin and there will be a need for another treatment, insulin according to the disease progression. At certain point, both types of diabetes are treated applying the same strategies. In this study, we followed another strategy by applying the use of apple cider vinegar in patient with type 1 diabetes, and patient with type 2 diabetes following getting each meal. The results showed that glucose levels were within reference range after five days. Taken together, the use of apple cider vinegar as a secondary treatment line with conventional diabetic treatment is promising and needs to be further investigated

Sign in / Sign up

Export Citation Format

Share Document