scholarly journals Plasma miR-126 levels and its genomic polymorphism SNP rs4636297 in Type 2 diabetes

Author(s):  
Monireh Rezai ◽  
Shirin Shahbazi ◽  
Nasrin Mansournia

Since the variation of microRNAs expression has been described in type2 diabetes, we aimed to evaluate the plasma levels of miR-126 with known roles in the angiogenesis. Genomic polymorphism of miR-126 (SNP rs4636297) was also assessed as it is involved in the processing of pri-miR-126 to mature microRNA.Genotyping of the SNP rs4636297 was carried out by PCR-RFLP using HaeII enzyme. Real-time PCR assay was applied to assess miR-126 expression, which the fold change in gene expression was calculated by the Relative Expression Software Tool (REST). Data analysis was performed using exact-like logistic regression, Fisher exact test and the elrm package with the R software. Our data indicated that the group with BMI greater than 30 was at greater risk of diabetes (odds ratio=14.4, p value=0.00), compared with the BMI=19-25. The mean fold decrease in miR-126 gene expression in diabetic samples relative to normal samples was 0.653 (95% confidence interval: 0.012 - 18.765). All patients with the lowest levels of miR-126, had experienced diabetic complications. Considering the AA genotype as the reference, the odds ratio of diabetic complications for the GG and AG genotype were 1.2 and 1.43, respectively. miR-126 is one of the key factors in predisposition to diabetes and diabetic complication. Since the lowest expression of miR-126 leads to the diabetic complications it can be concluded that genetic predisposing factors should be considered in the management and treatment of Type 2 diabetes.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hassan Awal ◽  
Seshagiri Rao Nandula ◽  
Nabanita KUNDU ◽  
Mona Fakhri ◽  
Beda Brichacek ◽  
...  

Introduction: CD34 +ve Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). Hypothesis: Canagliflozin, an SGLT2 inhibitor when added to other oral antidiabetic medication such Metformin, Insulin, GLP1-agonists, DPP-IV inhibitor, or sulfonylureas, may improve the cardiovascular risk by improving CD34+ EPCs function such as migration, colony formation and maturation towards endothelium. Methods: 29 subjects were enrolled in this 16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo. T2DM (30-70 years old), HbA1c of 6.5-10%, and all stages of CKD were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0, 8, and 16. A mixed model regression analysis was done with a p-value <0.05 considered significant. Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure. There was a reduction in blood glucose level (p=0.0047) and HbA1c (p=0.03). There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin. There is also an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA (p=0.049), VEGF receptor KDR (p=0.13), PECAM-1, a mature endothelial marker was also upregulated (p=0.002) and NOS3 (or eNOS) was also upregulated. There were no significant changes in CD34+ numbers by direct counting and parameters tested. We also tested for serum ketones bodies and found no difference at the dose tested. Data on urine podocyte specific exosome is pending Conclusions: Our study indicates that Canagliflozin improves several components of ECF by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes.


2021 ◽  
Author(s):  
Jyoti Rani ◽  
Anasuya Bhargav ◽  
Malabika Datta ◽  
Urmi Bajpai ◽  
Srinivasan Ramachandran

Abstract Adaptive immune response of the Th1 arm is the main defense against tuberculosis (TB). However, in Type 2 Diabetes Mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to TB and results in poor TB control. The molecular pathways causing susceptibility of diabetics to tuberculosis is not fully understood. Here, an integrative pathway-based approach is used to investigate the perturbed pathways in T2DM patients rendering susceptibility to TB. We obtained 36 genes implicated in the Type 2 diabetes associated tuberculosis (T2DMTB) from literature. Gene expression analysis on T2DM patients’ data (GSE28168) showed that DEFA1 is differentially expressed at Padj < 0.05. The genes CAMP, CD14, CORO1A, LAMP1, TLR4, IL17F and SOCS3 were differentially expressed in T2DM patients at P value < 0.05. 7 microRNAs associated with these T2DMTB genes were obtained from NetworkAnalyst and verified for their literature evidences. The hsa-miR-146a microRNA was differentially expressed at Padj < 0.05. The human host TB susceptibility genes TNFRSF10A, MSRA, GPR148, SLC37A3, PXK, PROK2, REV3L, PGM1, HIST3H2A, PLAC4, LETM2, EMP2 and were also differentially expressed at Padj < 0.05. We included all these genes and added the remaining 28 genes from the T2DMTB set and the rest of differentially expressed genes at Padj < 0.05 in STRING and obtained a well-connected network with high confidence score greater than 0.7. From this network we extracted the KEGG pathways at FDR < 0.05 and retained only Diabetes and TB pathways among the disease pathways. The network was simulated with BioNSi using gene expression data from GSE26168. The Necroptosis pathway showed the maximum perturbations in T2DM patients, followed by NOD-like receptor signaling, Toll-like receptor signaling, NF-kappa-B signaling and MAPK signaling. These pathways likely underlie susceptibility to TB in T2DM patients.


Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 96 ◽  
Author(s):  
Duygu Sak ◽  
Fusun Erdenen ◽  
Cuneyt Müderrisoglu ◽  
Esma Altunoglu ◽  
Volkan Sozer ◽  
...  

Background: Taurine has an active role in providing glucose homeostasis and diabetes causes a decline in taurine levels. This paper investigates the relationship between taurine and diabetic complications, patients’ demographic features, and biochemical parameters. Methods: Fifty-nine patients with type 2 diabetes mellitus (T2DM), and 28 healthy control subjects between the ages of 32 and 82 were included in the study. The mean age of subjects was 55.6 ± 10.3 and mean diabetes duration was 10.2 ± 6.0 years. The most commonly accompanying comorbidity was hypertension (HT) (64.5%, n = 38), and the most frequent diabetic complication was neuropathy (50.8%, n = 30). Plasma taurine concentrations were measured by an enzyme-linked immunoassay (ELISA) kit. Results: Plasma taurine concentrations were significantly lower in diabetic patients (0.6 ± 0.1 mmol/L) than controls (0.8 ± 0.2 mmol/L) and in hypertensive (0. 6 ± 0.1 mmol/L) patients (p = 0.000, p = 0.027 respectively). Conclusion: Plasma taurine levels were decreased in patients with T2DM and this was not related to FBG, HbA1c, and microalbuminuria. With regard to complications, we only found a correlation with neuropathy. We suggest that taurine levels may be more important in the development of diabetes; however, it may also have importance for the progression of the disease and the subsequent complications. We further assert that taurine measurement at different times may highlight whether there is a causal relationship in the development of complications.


2024 ◽  
Vol 84 ◽  
Author(s):  
A. Q. Alkhedaide ◽  
A. Mergani ◽  
A. A. Aldhahrani ◽  
A. Sabry ◽  
M. M. Soliman ◽  
...  

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.


2020 ◽  
Vol 7 (5) ◽  
pp. 754
Author(s):  
Damanpreet Singh ◽  
Gurinder Mohan ◽  
Arshdeep Bansal

Background: Hypothyroidism is an endocrine disorder resulting from deficiency of thyroid hormones, and Diabetes is a metabolic disorder that share the phenotype of hyperglycaemia. Both the endocrinopathies have been found to be associated with dyslipidaemia and atherosclerosis that result into various complications. Our aim was to assess the difference of dyslipidaemia in patients suffering from hypothyroidism with diabetes as compared to diabetes alone.Methods: Study was conducted in department of medicine in SGRDIMSR, Sri Amritsar. A total of 120 patients were enrolled for the present study, the one who presented to hospital from January 2018 to August 2019 diagnosed with diabetes mellitus type 2. The patients were divided into two groups. 60 patients having type 2 diabetes without hypothyroidism (control group). 60 patients having type 2 diabetes with hypothyroidism (study group). Fasting lipid profile were performed in both the groups and were analysed for the study.Results: Dyslipidaemia was seen more in study group as compared to control group with mean cholesterol of 488.3(±144.43) and mean triglyceride levels of 354.30(±128.57) in study  group as compared to control group with mean cholesterol and triglyceride levels of 179.7(±81.47) and 177.08(±118.18) with p-value of 0.001 and 0.01 respectively which were significant. Also, obesity and diabetic complication were more in patients of dual endocrinopathies as compared to diabetes alone which were also significant statistically.Conclusions: From our study it is concluded that type 2 diabetes with hypothyroidism causes more dyslipidaemia as compare to type 2 diabetes alone. So proper screening of thyroid profile of type 2 diabetic patients and its correction helps in achieving better lipidemic control which further prevent complications.


2020 ◽  
Author(s):  
Seshagiri Rao Nandula ◽  
Nabanita Kundu ◽  
Hassan Awal ◽  
Beda Brichacek ◽  
Mona Fakhri ◽  
...  

Abstract Background: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Effect of sodium glucose channel inhibitors (SGLT2 inhibitors) such as Canagliflozin (CG) on a cellular CVD risk indicator such as CD34+ve cells, in patients with T2DM with established CKD has not been explored,Methods: 29 subjects taking metformin and/or Insulin were enrolled in a 16 weeks, double blind, randomized placebo matched trial, with a low dose 100 mg CG compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 7–10%,. CD34+ cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done with p value less than 0.05 were considered significant.Results: Gene expression analysis of CD34+ve cells showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX). A significant increase in gene expression of endothelial markers PECAM1 (p=0.002), VEGF-A(p= 0.04) and CXCR4 receptor (p= 0.06) followed by an increase in migratory function of CD34+ve cells is observed in Canagliflozin treated group as compared to placebo group. A significant reduction in glucose (p=0.01) levels was observed along with improved systolic and diastolic blood pressure in the CG group. Significant increase in adiponectin (p=0.02) was also noted in treatment group. Urinary exosomal protein examining podocyte health (podocalyxin, Wilm’s tumor and nephrin) showed improvement.Conclusion: We conclude that Canagliflozin on addition to metformin and/or Insulin, in subjects with type 2 diabetes demonstrates a functional improvement of CD34+ Endothelial Progenitor Cell function and gene expression and improves endothelial function


2015 ◽  
Vol 23 (4) ◽  
pp. 603-610 ◽  
Author(s):  
Natália Chantal Magalhães da Silva ◽  
Érika de Cássia Lopes Chaves ◽  
Emilia Campos de Carvalho ◽  
Leonardo César Carvalho ◽  
Denise Hollanda Iunes

AbstractObjective: to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus.Method: this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value <0.05).Results: participants who received the therapy showed better scores in some impairment indicators related to skin and hair (hair growth, elasticity/turgor, hydration, perspiration, texture and integrity of the skin/ skin peeling).Conclusion: the foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 52-LB
Author(s):  
MAYSA SOUSA ◽  
ARITANIA SANTOS ◽  
MARIA ELIZABETH R. SILVA

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