Genetic variants in promoter regions associated with type 2 diabetes mellitus: A large‐scale meta‐analysis and subgroup analysis

2019 ◽  
Vol 120 (8) ◽  
pp. 13012-13025 ◽  
Author(s):  
Ling Wu ◽  
Chi Chiu Wang
Author(s):  
Hongshuo Shi ◽  
Yufan Liu ◽  
Min Peng ◽  
Zunqi Kan ◽  
Wenwen Li ◽  
...  

Objectives: Type 2 diabetes mellitus(T2DM) can accelerate the clinical process of atherosclerosis(AS). Dipeptidyl peptidase-4 inhibitors(DPP-4Is) have potential anti-AS effects. And, we completed a meta-analysis of the changes in carotid intima-media thickness(CIMT), flow-mediated dilation(FMD), and pulse wave velocity(PWV) of DPP-4Is to research the effect of DPP-4Is in the progression of AS in T2DM patients. Materials and methods: We included RCTs that evaluated the impact of DPP-4Is on CIMT, FMD, and PWV compared to other treatments from PubMed, Cochrane trials, and Embase database before October 31, 2020. We selected the random-effect model and calculated the weighted mean difference(WMD) to evaluate the effect of CIMT, FMD, and PWV in T2DM patients. Results:Through the meta-analysis, we found that DPP-4Is can significantly reduce CIMT in T2DM patients(WMD =-0.036, 95% CI:-0.055 to-0.017; p≤0.001). Based on the subgroup analysis, we found that CIMT was significantly decreased in patients with greater than 12 months of intervention and without cardiovascular diseases. Besides, we also found that DPP-4Is had a not significant efficacy on the improvement of FMD in T2DM patients(WMD=0.635, 95% CI: -0.112 to 1.383, p= 0.097). Our subgroup analysis showed that for T2DM patients who have cardiovascular diseases, DPP-4Is can significantly increase their FMD. In addition, we also found that DPP-4Is had an insignificant influence on PWV in T2DM patients(WMD= 0.424, 95% CI: -0.198 to 1.046, p= 0.18). but SGLT2 inhibitors may reduce the PWV of T2DM patients. Conclusions: DPP-4Is can alleviate the development of AS in T2DM patients to a certain extent by reducing CIMT. And, we believe that long-term use of DPP-4Is may be more helpful to alleviate the atherosclerotic development of T2DM without obvious cardiovascular history.


2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Jieyuan Cui ◽  
Xiaolin Zhang ◽  
Cheng Guo ◽  
Lin Zhang

Abstract Objectives: To evaluate the effects of the single-nucleotide polymorphism (SNP) rs1800795 in interieukin-6 (IL-6) gene on diabetic microvascular complications of Type 2 diabetes mellitus (T2DM), using statistical meta-analysis. Methods: Literature pertaining to the relationship between the SNP rs1800795 and microvascular complications of T2DM including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and foot disease was retrieved from PubMed, Web of Science Knowledge and SinoMed databases. Original information was analyzed using Stata 12.0, including meta-analysis statistics, test for heterogeneity, evaluation of publication bias and sensitivity. Subgroup analysis was conducted to assess the effect of specific factors on the corresponding results. Results: In total, 14 eligible articles were obtained. The SNP rs1800795 in IL-6 gene is not correlated with risk of microvascular complications in T2DM. Among the original literature, a genetic model (OR = 1.071, 95% CI: 0.681–1.685, P=0.767), an allelic genetic model (OR = 1.010, 95% CI: 0.959–1.063, P=0.703), a heterozygote genetic model (OR = 1.107, 95% CI: 0.916–1.339, P=0.292), a dominant genetic model (OR = 1.108, 95% CI: 0.885–1.387, P=0.372), and a recessive genetic model (OR = 0.978, 95% CI: 0.646–1.478, P=0.917) were included respectively. In the subgroup analysis by types of diabetic microvascular complications, we found no correlation between the SNP rs1000795 polymorphism and complications of T2DM in either the homozygote genetic model or the allelic genetic model (P<0.05). Conclusion: Our results demonstrate that rs1800795 polymorphism in IL-6 gene is not correlated with the susceptibility of microvascular complications of T2DM.


2020 ◽  
Vol 78 (1) ◽  
pp. 87-95
Author(s):  
Reagon Karki ◽  
Sumit Madan ◽  
Yojana Gadiya ◽  
Daniel Domingo-Fernández ◽  
Alpha Tom Kodamullil ◽  
...  

Background: Recent studies have suggested comorbid association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) through identification of shared molecular mechanisms. However, the inference is pre-dominantly literature-based and lacks interpretation of pre-disposed genomic variants and transcriptomic measurables. Objective: In this study, we aim to identify shared genetic variants and dysregulated genes in AD and T2DM and explore their functional roles in the comorbidity between the diseases. Methods: The genetic variants for AD and T2DM were retrieved from GWAS catalog, GWAS central, dbSNP, and DisGeNet and subjected to linkage disequilibrium analysis. Next, shared variants were prioritized using RegulomeDB and Polyphen-2. Afterwards, a knowledge assembly embedding prioritized variants and their corresponding genes was created by mining relevant literature using Biological Expression Language. Finally, coherently perturbed genes from gene expression meta-analysis were mapped to the knowledge assembly to pinpoint biological entities and processes and depict a mechanistic link between AD and T2DM. Results: Our analysis identified four genes (i.e., ABCG1, COMT, MMP9, and SOD2) that could have dual roles in both AD and T2DM. Using cartoon representation, we have illustrated a set of causal events surrounding these genes which are associated to biological processes such as oxidative stress, insulin resistance, apoptosis and cognition. Conclusion: Our approach of using data as the driving force for unraveling disease etiologies eliminates literature bias and enables identification of novel entities that serve as the bridge between comorbid conditions.


2019 ◽  
Vol 7 (1) ◽  
pp. e000728
Author(s):  
Sanbao Chai ◽  
Shuqing Yu ◽  
Zhirong Yang ◽  
Shanshan Wu ◽  
Le Gao ◽  
...  

ObjectivesTo evaluate the risk of cancers of digestive system with incretin-based therapies among patients with type 2 diabetes mellitus.Research design and methodsMedline, Embase, Cochrane Library and ClinicalTrials.gov databases were searched for randomized controlled clinical trials that compared incretin-based drugs with placebo or other antidiabetic drugs. Paired reviewers independently screened citations, extracted data and assessed risk of bias of included studies. Network meta-analysis was performed, followed by subgroup analysis. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence.ResultsA total of 84 studies (n=101 595) involving cancers of digestive system were identified (a median follow-up of 30 weeks). The risk of cancers of digestive system with incretin-based therapies was comparable with insulin (OR: 0.86, 95% CI 0.27 to 2.69), metformin (OR: 0.32, 95% CI 0.07 to 1.38), sodium-glucose co-transporter 2 (OR: 5.26, 95% CI 0.58 to 47.41), sulfonylureas (OR: 1.27, 95% CI 0.68 to 2.39), thiazolidinediones (OR: 0.42, 95% CI 0.13 to 1.42), alpha-glucosidase inhibitors (OR: 2.98, 95% CI 0.12 to 73.80), and placebo (OR: 0.87, 95% CI 0.71 to 1.05). The results of subgroup analysis based on the type of digestive system cancers indicated that incretin-based therapies did not increase the risk of gastrointestinal cancers, respectively. The results of subgroup analysis based on age, duration, mean HbA1c, trial duration, and sample size did not indicate the risk of digestive system cancers.ConclusionsModerate to high Grading of Recommendations Assessment, Development and Evaluation evidence suggests that incretin-based therapies were not associated with an increased risk of cancer of digestive system in patients with type 2 diabetes mellitus.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1159-P
Author(s):  
GLENN M. DAVIES ◽  
ANN MARIE MCNEILL ◽  
ELIZA KRUGER ◽  
STACEY L. KOWAL ◽  
FLAVIA EJZYKOWICZ ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2393-PUB
Author(s):  
KENICHIRO TAKAHASHI ◽  
MINORI SHINODA ◽  
RIKA SAKAMOTO ◽  
JUN SUZUKI ◽  
TADASHI YAMAKAWA ◽  
...  

Author(s):  
Arwa Aljabali ◽  
Roaa Maghrabi ◽  
Ahmad Shok ◽  
Ghufran Alshawmali ◽  
Abdullah Alqahtani ◽  
...  

2019 ◽  
Vol 18 (3) ◽  
pp. 247-255
Author(s):  
Sierra-Puente D. ◽  
Abadi-Alfie S. ◽  
Arakanchi-Altaled K. ◽  
Bogard-Brondo M. ◽  
García-Lascurain M. ◽  
...  

Spices such as cinnamon (Cinnamomum Spp.) have been of interest due to their phytochemical composition that exert hypoglycemic effects with potential for management of type 2 diabetes mellitus (T2DM). We summarize data from 27 manuscripts that include, one book chapter, 3 review articles, 10 randomized controlled trials, 4 systematic reviews with meta-analysis, and 9 preclinical studies. The most frequently used cinnamon variety was Cinnamomum cassia rather than the Cinnamomum zeylanicum, whereas outcomes were defined as fasting blood glucose, glycated hemoglobin, and oral glucose tolerance test. A great variability in methodology such as different doses (from 120 mg to 6 g), duration of intervention, data retrieved and use of different concomitant medication, were found to be key aspects of most of trials and systematic reviews with meta-analysis available to date. Low quality studies have been made in most cases with a lot of heterogeneity clouding significance of results. More research needs to be done in order to yield accurate evidence for evidence-based recommendations. Its use is not currently a reliable nor advisable option for the treatment of T2DM.


2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


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