The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Subsequent Development ◽  
Asian Population ◽  
Gstm1 Null Genotype ◽  
Increased Risk

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.

scholarly journals ABCA1 69C>T Polymorphism and the Risk of Type 2 Diabetes Mellitus: A Systematic Review and Updated Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ha Young Yoon ◽  
Min Hye Lee ◽  
Yubin Song ◽  
Jeong Yee ◽  
Gonjin Song ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Meta Analysis ◽  
Asian Population ◽  
Increased Risk ◽  
Β Cell Function

BackgroundThe ATP-binding cassette transporter A1 (ABCA1) is likely associated with the risk of type 2 diabetes mellitus (T2DM) via β cell function modification, but the evidence on the association remains unclear. This study aimed to investigate the relationship between the ABCA1 69C&gt;T polymorphism and the risk of T2DM through a systematic review and meta-analysis.Materials and MethodsThe PubMed, Web of Science, and Embase databases were searched for qualified studies published until August 2020. Studies that included the association between the ABCA1 69C&gt;T polymorphism and the risk of T2DM were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated.ResultsWe analyzed data from a total of 10 studies involving 17,742 patients. We found that the CC or CT genotype was associated with increased risk of T2DM than the TT genotype (OR, 1.41; 95% CI, 1.02-1.93). In the Asian population, the C allele carriers had a higher risk of T2DM than those with the TT genotype; the ORs of the CC and CT genotypes were 1.80 (95% CI, 1.21-2.68) and 1.61 (95% CI, and 1.29-2.01), respectively.ConclusionsThis meta-analysis confirmed that the ABCA1 69C&gt;T genotype showed a decrease risk of T2DM compared to the CC or CT genotypes.

scholarly journals TheType 2 Deiodinase Thr92Ala PolymorphismIs Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaowen Zhang ◽  
Jie Sun ◽  
Wenqing Han ◽  
Yaqiu Jiang ◽  
Shiqiao Peng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Meta Analysis ◽  
Increased Risk ◽  
Design And Methods ◽  
Hba1c Levels

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels.Design and Methods.The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed.Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels.Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

scholarly journals The association between insulin therapy and depression in patients with type 2 diabetes mellitus: a meta-analysis

BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e020062 ◽  
Author(s):  
Xiaosu Bai ◽  
Zhiming Liu ◽  
Zhisen Li ◽  
Dewen Yan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Therapy ◽  
Depressive Disorders ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Cochrane Library ◽  
Increased Risk

ObjectivesSeveral patients with type 2 diabetes mellitus (T2DM) have depressive disorders. Whether insulin treatment was associated with increased risk of depression remains controversial. We performed a meta-analysis to evaluate the association of insulin therapy and depression.DesignA meta-analysis.MethodsWe conducted a systematic search of PubMed, PsycINFO, Embase and the Cochrane Library from their inception to April 2016. Epidemiological studies comparing the prevalence of depression between insulin users and non-insulin users were included. A random-effects model was used for meta-analysis. The adjusted and crude data were analysed.ResultsTwenty-eight studies were included. Of these, 12 studies presented with adjusted ORs. Insulin therapy was significantly associated with increased risk of depression (OR=1.41, 95% CI 1.13 to 1.76, p=0.003). Twenty-four studies provided crude data. Insulin therapy was also associated with an odds for developing depression (OR=1.59, 95% CI 1.41 to 1.80, p<0.001). When comparing insulin therapy with oral antidiabetic drugs, significant association was observed for adjusted (OR=1.42, 95% CI 1.08 to 1.86, p=0.008) and crude (OR=1.61, 95% CI 1.35 to 1.93, p<0.001) data.ConclusionsOur meta-analysis confirmed that patients on insulin therapy were significantly associated with the risk of depressive symptoms.

Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting

2021 ◽  
Author(s):  
Siphosethu Cassandra Maphumulo ◽  
Etheresia Pretorius
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systemic Inflammation ◽  
Blood Cells ◽  
Low Grade ◽  
Chronic Hyperglycemia ◽  
Increased Risk

AbstractType 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.

scholarly journals Associations of KCNQ1 Polymorphisms with the Risk of Type 2 Diabetes Mellitus: An Updated Meta-Analysis with Trial Sequential Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiao-xuan Yu ◽  
Min-qi Liao ◽  
Yu-fei Zeng ◽  
Xu-ping Gao ◽  
Yan-hua Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gene Polymorphisms ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Asian Population ◽  
Trial Sequential Analysis ◽  
Case Control Studies

Background. Previous studies have examined the role of the KQT-like subfamily Q member1 (KCNQ1) gene polymorphisms on the risk of type 2 diabetes mellitus (T2DM), but the findings are inconclusive. Objective. To examine the association between the KCNQ1 gene polymorphisms and the risk of T2DM using an updated meta-analysis with an almost tripled number of studies. Methods. Five electronic databases, such as PubMed and Embase, were searched thoroughly for relevant studies on the associations between seven most studied KCNQ1 gene polymorphisms, including rs2237892, rs2237897, rs2237895, rs2283228, rs231362, rs151290, and rs2074196, and T2DM risk up to September 14, 2019. The summary odds ratios (ORs) with their 95% confidence intervals (CIs) were applied to assess the strength of associations in the random-effects models. We used the trial sequential analysis (TSA) to measure the robustness of the evidence. Results. 49 publications including 55 case-control studies (68,378 cases and 66,673 controls) were finally enrolled. In overall analyses, generally, increased T2DM risk was detected for rs2237892, rs2237895, rs2283228, rs151290, and rs2074196, but not for rs231362 under all genetic models. The ORs and 95% CIs for allelic comparison were 1.23 (1.14-1.33) for rs2237892, 1.21 (1.16-1.27) for rs2237895, 1.27 (1.11-1.46) for rs2237897, 1.25 (1.09-1.42) for rs2283228, 1.14 (1.03-1.27) for rs151290, 1.31 (1.23-1.39) for rs2074196, and 1.16 (0.83, 1.61) for rs231362. Stratified analyses showed that associations for rs2237892, rs2237895, rs2283228, and rs151290 were more evident among Asians than Caucasians. TSA demonstrated that the evidence was sufficient for all polymorphisms in this study. The genotypes of the three SNPs (rs2237892, rs2283228, and rs231362) were significantly correlated with altered KCNQ1 gene expression. Conclusion. This meta-analysis suggested that KCNQ1 gene polymorphisms (rs2237892, rs2283228, rs2237895, rs151290, and rs2074196) might be the susceptible factors for T2DM, especially among Asian population.

P2482Sex-based differences in cardioprotective role of SGLT-2 inhibitors in patients with type 2 diabetes mellitus

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Madan ◽  
S Sohal ◽  
B Parapid ◽  
L Sperling ◽  
J L Januzzi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Mixed Effect ◽  
Pooled Data ◽  
Major Cardiovascular Events ◽  
Effect Model

Abstract Background Randomized studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce major cardiovascular events in patients with type 2 diabetes mellitus. However, it is not known whether there are significant sex-based differences in the cardioprotective role of SGLT-2 inhibitors. Purpose To investigate whether sex differences exist in reduction of major cardiovascular events (MACE)in patients with type 2 diabetes mellitus when treated with SGLT2i. Methods A comprehensive PubMed search was conducted using keywords, (“Diabetes” AND (“Dapagliflozin” OR “Empagliflozin” OR “Canagliflozin” OR “Ertugliflozin”) AND “Outcomes”) that resulted in a total of 221 studies. Studies were included in our meta-analysis if they were randomized controlled trials, placebo-controlled, reported MACE as the primary outcome and reported sex-based subgroup analyses of these outcomes. Only 2 RCTs (EMPA-REG and DECLARE-TIMI 58) met our inclusion criteria.The sex-based event data for both trials was pooled to calculate risk ratios (RR) with 95% confidence intervals (CI). Analyses was performed using Comprehensive Meta-analysis (CMA) software. Fixed effect models, random effect models and mixed effect models were used. Results Pooled datafrom the 2 RCTs (EMPA-REG and DECLARE-TIMI 58) resulted in a total of 24,180 patients who were included in our primary analysis. Of these, 2331 patients were reported to have MACE. In our pooled data, SGLT2i reduced MACE in patients with diabetes with an overall risk ratio of 0.92 (0.85–0.99), p=0.03 (I2=0, p=0.31)using fixed effect model (Table 1). We also performed subgroup analysis of the pooled data categorizing by sex and using mixed effect model. Our subgroup analysis by sex showed a Q statistic of 1.88 with p-value of 0.17 suggesting that there is no significant difference in MACE reduction between men and women with diabetes when treated with SGLT2i. However, on further analyzing the sex differences in the individual trials, we found that women may have greater reduction in MACE compared with their male counterparts (RR in females: 0.66 (0.42–1.04); RR in males: 0.92 (0.84–1.00)), however this finding did not meet statistical significance (Table 2). Conclusion Our meta-analysis included the pooled data from 2 major RCTs (EMPA-REG and DECLARE-TIMI 58) assessing the cardioprotective role of SGLT2i in diabetic patients and shows that SGLT2i significantly reduce the risk of major adverse CV events in patients with type 2 diabetes mellitus. However, we did not find any significant sex-based differences in reduction of MACE between men and women with diabetes when treated with SGLT2i.

scholarly journals The Role of Combined SGLT1/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Bertram Pitt ◽  
Gabriel Steg ◽  
Lawrence A. Leiter ◽  
Deepak L. Bhatt
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Relative Increase ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Sglt2 Inhibition

Abstract Purpose In patients with type 2 diabetes mellitus (T2DM), both sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have demonstrated significant improvements in cardiovascular and kidney outcomes independent of their glycemic benefits. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings. Methods and Results Thus far, the results from SCORED and SOLOIST (trials studying the SGLT1/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding. Conclusions The role of SGLT1/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.

scholarly journals Different Associations Between CDKAL1 Variants and Type 2 Diabetes Mellitus Susceptibility: A Meta-analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiaoli Zeng ◽  
Dehua Zou ◽  
Shanshan Gu ◽  
Fengqiong Han ◽  
Shilin Cao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Regulatory Subunit ◽  
Dominant Model ◽  
Increased Risk ◽  
Pathogenesis Related Protein ◽  
Allele Model

Background:CDK5 regulatory subunit associated protein 1 like 1 (CDKAL1) is a major pathogenesis-related protein for type 2 diabetes mellitus (T2DM). Recently, some studies have investigated the association of CDKAL1 susceptibility variants, including rs4712523, rs4712524, and rs9460546 with T2DM. However, the results were inconsistent. This study aimed to evaluate the association of CDKAL1 variants and T2DM patients.Methods: A comprehensive meta-analysis was performed to assess the association between CDKAL1 SNPs and T2DM among dominant, recessive, additive, and allele models.Results: We investigated these three CDKAL1 variants to identify T2DM risk. Our findings were as follows: rs4712523 was associated with an increased risk of T2DM for the allele model (G vs A: OR = 1.172; 95% CI: 1.103–1.244; p &lt; 0.001) and dominant model (GG + AG vs AA: OR = 1.464; 95% CI: 1.073–1.996; p = 0.016); rs4712524 was significantly associated with an increased risk of T2DM for the allele model (G vs A: OR = 1.146; 95% CI: 1.056–1.245; p = 0.001), additive model (GG vs AA: OR = 1.455; 95% CI: 1.265–1.673; p &lt; 0.001) recessive model (GG vs AA + AG: OR = 1.343; 95% CI: 1.187–1.518; p &lt; 0.001) and dominant model (GG + AG vs AA: OR = 1.221; 95% CI: 1.155–1.292; p &lt; 0.001); and rs9460546 was associated with an increased risk of T2DM for the allele model (G vs T: OR = 1.215; 95% CI: 1.167–1.264; p = 0.023). The same results were found in the East Asian subgroup for the allele model.Conclusions: Our findings suggest that CDKAL1 polymorphisms (rs4712523, rs4712524, and rs9460546) are significantly associated with T2DM.

Significant Association between Microrna Gene Polymorphisms and Type 2 Diabetes Mellitus Susceptibility in Asian Population: A Meta-Analysis

2020 ◽  
Author(s):  
Zhifang DENG ◽  
Wenqi GAO ◽  
Wei LUO ◽  
Li AI ◽  
Min HU
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Asian Population ◽  
Healthy Population ◽  
Nucleotide Polymorphisms ◽  
Microrna Gene

Background: The gene polymorphisms in microRNA might relate to susceptibility of type 2 diabetes mellitus (T2DM). However, the results of existing studies were inconsistent and obscure. To investigate the precise associations between microRNA gene polymorphisms and T2DM risk, the present meta-analysis was performed. Methods: The literatures were searched from four electronic databases, PubMed, Embase, CNKI and Wanfang. Subsequently, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were both used to evaluate the associations between two single nucleotide polymorphisms (SNPs) (microRNA146a rs2910164 (G>C), microRNA124a rs531564 (C>G)) and risk of T2DM in Asian population. Results: Totally, there were 4 studies included in our present analysis in the language of English and Chinese. There were partly significant associations between susceptibility of T2DM and SNPs (microRNA146a rs2910164 (G>C), microRNA124a rs531564 (C>G)). The G allele in microRNA146a rs2910164 (G>C) and C allele in microRNA124a rs531564 (C>G) both presented remarkably reduced risk of T2DM when compared with the healthy population. Conclusion: The microRNA146a rs2910164 (G allele) and microRNA124a rs531564 (C allele) might function as protective factors in the pathogenetic process of T2DM in Asian population.

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