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 ◽  
...  

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 < 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 < 0.001) recessive model (GG vs AA + AG: OR = 1.343; 95% CI: 1.187–1.518; p < 0.001) and dominant model (GG + AG vs AA: OR = 1.221; 95% CI: 1.155–1.292; p < 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.

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Xiaoliang Guo ◽  
Chenxi Li ◽  
Jiawei Wu ◽  
Qingbu Mei ◽  
Chang Liu ◽  
...  

Abstract Tumor necrosis factor-α (TNF-α) is involved in insulin resistance and has long been a candidate gene implicated in type 2 diabetes mellitus (T2DM), however the association between TNF-α polymorphisms -308G/A and -238G/A and T2DM remains controversial. The present study sought to verify associations between these polymorphisms and T2DM susceptibility using a meta-analysis approach. A total of 49 case–control studies were selected up to October 2018. Statistical analyses were performed by STATA 15.0 software. The odds ratios (ORs) and 95% confidence intervals were calculated to estimate associations. Meta-analyses revealed significant associations between TNF-α −308G/A and T2DM in the allele model (P=0.000); the dominant model (P=0.000); the recessive model (P=0.001); the overdominant model (P=0.008) and the codominant model (P=0.000). Subgroup analyses also showed associations in the allele model (P=0.006); the dominant model (P=0.004) and the overdominant model (P=0.005) in the Caucasian and in the allele model (P=0.007); the dominant model (P=0.014); the recessive model (P=0.000) and the codominant model (P=0.000) in the Asian. There were no associations between TNF-α −238G/A and T2DM in the overall and subgroup populations. Meta-regression, sensitivity analysis and publication bias analysis confirmed that results and data were statistically robust. Our meta-analysis suggests that TNF-α −308G/A is a risk factor for T2DM in Caucasian and Asian populations. It also indicates that TNF-α −238G/A may not be a risk factor for T2DM. More comprehensive studies will be required to confirm these associations.


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.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaowen Zhang ◽  
Jie Sun ◽  
Wenqing Han ◽  
Yaqiu Jiang ◽  
Shiqiao Peng ◽  
...  

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.


BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e020062 ◽  
Author(s):  
Xiaosu Bai ◽  
Zhiming Liu ◽  
Zhisen Li ◽  
Dewen Yan

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ha Young Yoon ◽  
Min Hye Lee ◽  
Yubin Song ◽  
Jeong Yee ◽  
Gonjin Song ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qiaoli Zeng ◽  
Dehua Zou ◽  
Qiaodi Zeng ◽  
Xiaoming Chen ◽  
Yue Wei ◽  
...  

Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T &gt; C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk.Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models).Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082–1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095–5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055–2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148–3.257, p = 0.013) with random effects model. After omitting Gouda’s study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004–1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model.Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.


2020 ◽  
Vol 107 (5) ◽  
pp. 453-463
Author(s):  
Panagiotis Anagnostis ◽  
Nifon K. Gkekas ◽  
Charoula Achilla ◽  
Georgia Pananastasiou ◽  
Polyxeni Taouxidou ◽  
...  

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e029073 ◽  
Author(s):  
Xianzhe Wang ◽  
Jiabin Liu ◽  
Lijin Huang ◽  
Hai Zeng ◽  
Guoxin He ◽  
...  

IntroductionType 2 diabetes mellitus (T2DM) is a substantial health problem worldwide. Pre-diabetic state is associated with increased risk for the development of diabetes. There are various pharmacological therapies with glucose-lowering activity for diabetes prevention. Of those, most are being compared with placebo instead of active agents. The relative effects and safety of different glucose-lowering drugs still remain uncertain. To address this gap, we will conduct a systematic review and network meta-analysis (NMA) to evaluate comparative efficacy and safety of glucose-lowering agents for T2DM prevention in patients with pre-diabetes.Methods and analysisPubMed, the Cochrane library and Embase will be searched from inception to December 2019 for relevant randomised controlled trials (RCTs) that examined anti-diabetic drugs for diabetes prevention in patients with pre-diabetes. Two reviewers working independently will screen titles, abstracts and full papers. Data extraction will also be completed by two independent authors. The primary outcome will be the incidence of T2DM in patients with pre-diabetes at baseline. Secondary outcomes will include the achievement of normoglycaemia, all-cause mortality, cardiovascular mortality and hypoglycaemic event. Pairwise meta-analysis and NMA will be conducted for each outcome using a frequentist random-effects model. Additionally, subgroup analyses will also be performed. The comparison-adjusted funnel plot will be used to assess publication bias. The overall quality of evidence will be rated with the Grading of Recommendations Assessment, Development and Evaluation framework. Data analysis will be conducted using Stata V.14.0.Ethics and disseminationEthics approval is not required. We plan to submit the results of this study to a peer-review journal.PROSPERO registration numberCRD42019119157.


2021 ◽  
Vol 10 (3) ◽  
pp. 565
Author(s):  
Ronald Pratama Adiwinoto ◽  
Robert Dwitama Adiwinoto ◽  
Jongky Hendro Prajitno

Diabetic retinopathy (DR) is the major cause of visual impairment in the working-age population with type 2 diabetes mellitus (T2DM). Magnesium (Mg) is involved in various metabolic processes and in experimental animal studies; Mg has shown essential roles in physiological eye function. Magnesium deficiency is common in T2DM; therefore we analyzed the association between serum Mg status and the presence of DR in T2DM patients. Systematic literature searching in several databases, from 1988 to September 2020, was performed using search terms: “serum magnesium” or “hypomagnesemia” and “diabetic retinopathy” or “retinopathy”. A total of 3,227 patients from 17 studies were included in this meta-analysis. Hypomagnesemia was associated with increased risk of developing DR (OR 4.52 [2.08, 9.81], p=0.0001) in T2DM patients. Serum Mg levels also lower in patients with DR than those without DR (MD –0.30 mg/dL [–0.44, –0.15], p&lt;0.0001). Additionally, serum Mg levels were lower in patients with proliferative DR (PDR) than those with non-proliferative DR (NPDR) (MD-0.21 mg/dL [–0.34, –0.09], p=0.0009). Leave-one-out sensitivity analysis did not change the overall effect. Hypomagnesemia or low serum Mg levels in T2DM patients increased the risk of developing DR.


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