scholarly journals Recessive genetic effects on type 2 diabetes-related metabolites in a consanguineous population

2019 ◽  
Author(s):  
Ayşe Demirkan ◽  
Jun Liu ◽  
Najaf Amin ◽  
Jan B van Klinken ◽  
Ko Willems van Dijk ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Autosomal Recessive ◽  
Metabolic Diseases ◽  
Genetic Model ◽  
Autosomal Recessive Inheritance ◽  
P Value ◽  
Recessive Mutations ◽  
Nominal Significance ◽  
The Central Nervous System

AbstractAutozygosity, meaning inheritance of an ancestral allele in the homozygous state is known to lead bi-allelic mutations that manifest their effects through the autosomal recessive inheritance pattern. Autosomal recessive mutations are known to be the underlying cause of several Mendelian metabolic diseases, especially among the offspring of related individuals. In line with this, inbreeding coefficient of an individual as a measure of cryptic autozygosity among the general population is known to lead adverse metabolic outcomes including Type 2 diabetes (T2DM); a multifactorial metabolic disease for which the recessive genetic causes remain unknown. In order to unravel such effects for multiple metabolic facades of the disease, we investigated the relationship between the excess of homozygosity and the metabolic signature of T2DM. We included a set of 53 metabolic phenotypes, including 47 metabolites, T2DM and five T2DM risk factors, measured in a Dutch genetic isolate of 2,580 people. For 20 of these markers, we identified 29 regions of homozygous (ROHs) associated with the nominal significance of P-value < 1.0 × 10−3. By performing association according to the recessive genetic model within these selected regions, we identified and replicated two intronic variants: rs6759814 located in KCNH7 associated with valine and rs1573707 located in PTPRT associated with IDL-free cholesterol and IDL-phospholipids. Additionally, we identified a rare intronic SNV in TBR1 for which the homozygous individuals were enriched for obesity. Interestingly, all three genes are mainly neuronally expressed and pointed out the involvement of glutamergic synaptic transmission pathways in the regulation of metabolic pathways. Taken together our study underline the additional benefits of model supervised analysis, but also seconds the involvement of the central nervous system in T2DM and obesity pathogenesis.

scholarly journals Effect of inbreeding on type 2 diabetes-related metabolites in a Dutch genetic isolate

2019 ◽  
Author(s):  
Ayşe Demirkan ◽  
Jun Liu ◽  
Najaf Amin ◽  
Ko Willems van Dijk ◽  
Cornelia M. van Duijn
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Autosomal Recessive ◽  
Metabolic Diseases ◽  
Additive Model ◽  
Autosomal Recessive Inheritance ◽  
Genetic Isolate ◽  
Remarkable Effect ◽  
Recessive Mutations

AbstractAutozygosity, meaning inheritance of an ancestral allele in the homozygous state is known to lead bi-allelic mutations that manifest their effects through the autosomal recessive inheritance pattern. Autosomal recessive mutations are known to be the underlying cause of several Mendelian metabolic diseases, especially among the offspring of related individuals. In line with this, inbreeding coefficient of an individual as a measure of cryptic autozygosity among the general population is known to lead adverse metabolic outcomes including type 2 diabetes (T2DM), a multifactorial metabolic disease for which the recessive genetic causes remain unknown. In order to unravel such effects for multiple metabolic facades of the disease, we investigated the relationship between the excess of homozygosity and the metabolic signature of T2DM. We included a set of heritable 143 circulating markers associated with fasting glucose in a Dutch genetic isolate Erasmus Rucphen Family (ERF) of up to 2,580 individuals. We calculated individual whole genome-based, exome-based and pedigree-based inbreeding coefficients and tested their influence on the T2DM-related metabolites as well as T2DM risk factors. We also performed model supervised genome-wide association analysis (GWAS) for the metabolites which significantly correlate with inbreeding values. Inbreeding value of the population significantly and positively correlated with associated with risk factors of T2DM: body-mass index (BMI), glucose, insulin resistance, fasting insulin and waist-hip ratio. We found that inbreeding influenced 32.9% of the T2DM-related metabolites, clustering among chemical groups of lipoproteins, amino-acids and phosphatidylcholines, whereas 80 % of these significant associations were independent of the BMI. The most remarkable effect of inbreeding is observed for S-HDL-ApoA1, for which we show evidence of the novel DISP1 genetic region discovered by model supervised GWAS, in the ERF population. In conclusion, we show that inbreeding effects human metabolism and genetic models other than the globally used additive model is worth considering for study of metabolic phenotypes.

scholarly journals TYPE 2 DIABETES MELLITUS ON TRIGLYCERIDE LEVELS AND BLOOD PRESSURE

2019 ◽  
Vol 1 (1) ◽  
pp. 11-16
Author(s):  
Wirawan Anggorotomo ◽  
Tessa Sjahriani ◽  
Masroni Masroni
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Frequency Distribution ◽  
Metabolic Diseases ◽  
P Value ◽  
Chi Square ◽  
Chi Square Analysis

Background: Diabetes Mellitus (DM) is a group of metabolic diseases characterized by an abnormality of insulin secretion, insulin work, or both. DM cases in Indonesia as many as 8,5 million cases in 2013. Prevalence based on diagnosis or symptoms according to the health departement of 2,1%.Purpose: To know the correlation of type 2 diabetes mellitus on triglyceride levels and blood pressureMethods: This study used secondary data derived from the medical record status of patients with diabetes mellitus. The method used is analytic observational with cross sectional approach. Sampling technique using purposive sampling. The population of this study is the diabetes mellitus type 2 in 2017 as many as 151. Sample of 109 respondents. Data analyzed by univariate and bivariate using Chi Square analysis.Results: The frequency of respondent characteristic on female gender as much 57,8%, based on age group >45 old counted 58,7%. Blood pressure frequency distribution found hypertension as much 63,3%. High frequency distribution of triglyceride levels is 67,9%. The Chi Square analysis result there is a significant correlation of type 2 diabetes mellitus on triglyceride levels and blood pressure with Odds Ratio 6,865 with p-value of 0,009.

Mutations of mtDNA in some vascular and metabolic diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Anastasia I. Ryzhkova ◽  
Vasily V. Sinyov ◽  
Marina D. Sazonova ◽  
Tatiana V. Kirichenko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Chronic Diseases ◽  
Metabolic Diseases ◽  
Present Review ◽  
Mtdna Mutations

Background: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and as a result, death.In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies and type 2 diabetes mellitus. Objective: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis, Results: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension and various types of cardiomyopathies. Conclusion: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for treatment of these pathologies. MtDNA mutations associated withthe absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of diseases of vascular and metabolic genesis.

scholarly journals Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

2021 ◽  
Vol 9 (1) ◽  
pp. e001948
Author(s):  
Marion Denos ◽  
Xiao-Mei Mai ◽  
Bjørn Olav Åsvold ◽  
Elin Pettersen Sørgjerd ◽  
Yue Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Family History ◽  
Genetic Predisposition ◽  
Effect Modification ◽  
P Value ◽  
Family History Of Diabetes ◽  
Increased Risk ◽  
History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

scholarly journals Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 58 ◽  
Author(s):  
Michael D. Schaid ◽  
Yanlong Zhu ◽  
Nicole E. Richardson ◽  
Chinmai Patibandla ◽  
Irene M. Ong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Prostaglandin E2 ◽  
Genetic Model ◽  
Cell Mass ◽  
Arachidonic Acid Metabolite ◽  
Β Cell ◽  
Human Organ ◽  
Cell Dysfunction ◽  
Primary Mouse

The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the Ptger3 gene, in the loss of functional β-cell mass in Type 2 diabetes (T2D). The primary endogenous EP3 ligand is the arachidonic acid metabolite prostaglandin E2 (PGE2). Expression of the pancreatic islet EP3 and PGE2 synthetic enzymes and/or PGE2 excretion itself have all been shown to be upregulated in primary mouse and human islets isolated from animals or human organ donors with established T2D compared to nondiabetic controls. In this study, we took advantage of a rare and fleeting phenotype in which a subset of Black and Tan BRachyury (BTBR) mice homozygous for the Leptinob/ob mutation—a strong genetic model of T2D—were entirely protected from fasting hyperglycemia even with equal obesity and insulin resistance as their hyperglycemic littermates. Utilizing this model, we found numerous alterations in full-body metabolic parameters in T2D-protected mice (e.g., gut microbiome composition, circulating pancreatic and incretin hormones, and markers of systemic inflammation) that correlate with improvements in EP3-mediated β-cell 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.

PREVALENCE OF HYPERTENSION AMID PATIENTS WITH TYPE-2 DIABETES MELLITUS- AT A TERTIARY LEVEL HOSPITAL IN CENTRAL INDIA

2021 ◽  
pp. 57-59
Author(s):  
Hakimuddin Malvi ◽  
Syed Maqsood Husain
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Central India ◽  
P Value ◽  
Tertiary Level ◽  
Cross Sectional ◽  
Study Results ◽  
Level Hospital

Background: India has been recognized as the diabetes capital of the world by the year of 2025 Hypertension is a signicant danger factor for cardiovascular infection, stroke and ischemic coronary illness. Objective: The aim of this paper is prevalence of hypertension amid patients with type 2 diabetes mellitus- at a tertiary level hospital in central India. Methods: Present work is hospital based cross-sectional study was conduct in Chirayu Medical College & Hospital, Bhopal. The study population consisted of total 300 subjects. Data obtained directly from patients and patients medical les, and the following data were included in the study . Results: The results showed that the after using chi-square test we found that hypertension was signicantly higher p value(<0.05) among female patients (69%),patients with long duration diabetes (77%)10 years and more, also it was signicantly higher among patients with current smokers (69%). Conclusion: In this study the prevalence of hypertension is increasing in patient with T2DM. Hypertension was the most danger factor for micro vascular and macro vascular confusion of T2DM.

scholarly journals A study of cardiological autonomic neuropathy in Type 2 Diabetes Mellitus with reference to QT interval for its diagnosis

2019 ◽  
Vol 7 (7) ◽  
pp. 2574
Author(s):  
Lakshmi Priya Inapakolla ◽  
Ramgopal Teja Kotla
Keyword(s):  
Type 2 Diabetes ◽  
Autonomic Neuropathy ◽  
Autonomic Dysfunction ◽  
Cardiovascular Autonomic Neuropathy ◽  
Cardiac Autonomic Neuropathy ◽  
P Value ◽  
Qtc Interval ◽  
Duration Of Diabetes ◽  
Cardiac Autonomic Dysfunction

Background: Presence of cardiac autonomic neuropathy (CAN) is responsible for silent myocardial infarction and sudden death in diabetics. Hence recognizing cardiac dysautonomia early, which is asymptomatic will help to delay or arrest its progression.Methods: A cross-sectional study to evaluate the Prevalence of Cardiovascular Autonomic Neuropathy in Type 2 diabetes and correlate it with duration of Diabetes and to investigate the relationship between cardiac autonomic dysfunction and corrected QT interval.Results: In the study population, the prevalence of definite CAN was 8%, 24% and 58% in group A, B and C respectively. The prevalence of definite CAN increases with increase in duration of diabetes. P value <0.001 significant.Conclusions: A significant correlation is present between Cardiovascular autonomic dysfunction and QTc prolongation. QTc interval in the ECG can be used to diagnose Cardiovascular autonomic neuropathy with a reasonable sensitivity and specificity.

scholarly journals FAKTOR DURASI MENDERITA DM TIPE 2 MEMPENGARUHI PERUBAHAN KEMAMPUAN EFIKASI DIRI

2020 ◽  
Vol 8 (01) ◽  
pp. 52-69
Author(s):  
Nurul Kartika Sari ◽  
Rivan Firdaus
Keyword(s):  
Type 2 Diabetes ◽  
Sex Education ◽  
Significant Relationship ◽  
Self Efficacy ◽  
Sampling Technique ◽  
P Value ◽  
Cross Sectional ◽  
Type 2 Dm ◽  
As Stress

Background: Diabetes Mellitus (DM) cases increased by 776 cases from the previous year based on data from Abdul Wahab Sjahranie Regional Hospital. There are many changes that occur in the life of people with type 2 diabetes, such as stress, anxiety, anger, and feeling useless. These problems can be minimized if the patient also has the knowledge and ability as well as good self-efficacy to manage the disease by doing self-care. Aim: To analyze the factors associated with the self-efficacy of type 2 DM patients. Methods: a quantitative study with a cross sectional approach. The purposive sampling technique for Type 2 DM patients at Abdul Wahab Sjahranie Hospital Samarinda, totaling 60 respondents from September-October 2018. Results: showed a significant relationship between duration of suffering and self-efficacy of DM patients with a p value <0.001, and there was no significant relationship between age, sex, education level, knowledge, motivation and self-efficacy with a p value> 0.001. Conclusion: The duration of type 2 diabetes is related to the patient's self-efficacy ability.  

scholarly journals Estimation of Aldose Reductase Activity and Malondialdehyde Levels in Patients with Type 2 Diabetes Mellitus

2019 ◽  
Vol 12 (2) ◽  
pp. 1001-1007
Author(s):  
Sandeep Kumar ◽  
Ajay Kumar ◽  
Mohammad Mustufa Khan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Sugar ◽  
Aldose Reductase ◽  
Pearson Correlation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
P Value ◽  
Thiobarbituric Acid Reactive Substance

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia due to insufficient secretion or action of insulin.Elevated oxidative stress and diminished antioxidants may play an important role to develop T2DM and its complications. Aldose reductase (AR) enzyme plays a key role in the reduction of glucose to sorbitol by Polyol pathway. To estimate the AR activity and malondialdehyde (MDA) levels and in patients with T2DM. In this case-control study, a total number of 60 subjects (30 T2DM and 30 age-matched controls) wererecruited.Fasting blood sugar (FBS), Post-Prandial blood sugar (PPBS), AR activity and MDA levels were estimated in all the subjects. The AR activity was estimated by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidation method. The plasma MDA levels were estimated by the thiobarbituric acid reactive substance (TBARS) method. For Statistical analysis, all the data were compared between the two groups by using unpaired t-test. Pearson correlation coefficient was calculated among T2DM. A P value <0.05 was considered as statistically significant for all data analyzed. The mean of FBS, PPBS, AR activity, and MDA levels were found significantly high in T2DM as compared to controls (P<0.001, P<0.001, P<0.001, P<0.001, respectively). A significant positive correlation was found between FBS and PPBS among T2DM (r=0.71, P<0.01). However, There was no significant correlation found between AR activity and MDA level among T2DM (r=0.002, P>0.05). Results showed thatthe mean of FBS, PPBS, AR activity, and MDA levels were found significantly higher in T2DM than controls. There was no significant correlation found between AR activity and MDA level among T2DM.

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