Effect of metabolites levels on type 2 diabetes mellitus and glycemic traits: a Mendelian randomization study

2021 ◽  
Author(s):  
Yue Sun ◽  
Ya-Ke Lu ◽  
Hao-Yu Gao ◽  
Yu-Xiang Yan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Significance Level ◽  
Inverse Variance ◽  
Meta Analyses

Abstract Objective To assess the causal associations of plasma levels of metabolites with type 2 diabetes mellitus (T2DM) and glycemic traits. Methods Two-sample mendelian randomization (MR) was conducted to assess the causal associations. Genetic variants strongly associated with metabolites at genome-wide significance level (P < 5 × 10 −8) were selected from public GWAS, and SNPs of Outcomes were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for T2DM and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the fasting glucose, insulin and HbA1c. The Wald ratio and inverse-variance weighted methods were used for analyses, and MR-Egger was used for sensitivity analysis. Results The β estimates per 1 SD increasement of arachidonic acid (AA) level was 0.16 (95% CI: 0.078, 0.242; P<0.001). Genetic predisposition to higher plasma AA levels were associated with higher FG levels (β 0.10 [95%CI: 0.064, 0.134], P<0.001), higher HbA1c levels (β 0.04 [95%CI: 0.027, 0.061]) and lower FI levels (β -0.025 [95%CI: -0.047, -0.002], P=0.033). Besides, 2-hydroxybutyric acid (2-HBA) might have positive causal effect on glycemic traits. Conclusions Our findings suggest that AA and 2-HBA may have the causal associations on T2DM and glycemic traits. It is beneficial for clarifying the pathogenesis of T2DM, which would be valuable for early identification and prevention for T2DM.

scholarly journals Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Abraham Nigussie Mekuria ◽  
Yohanes Ayele ◽  
Assefa Tola ◽  
Kirubel Minsamo Mishore
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cancer Incidence ◽  
Lower Risk ◽  
Meta Analysis ◽  
Random Effects Model ◽  
Inverse Variance ◽  
Risk Of Cancer

Background. Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus. Objective. A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients. Methods. Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using I2 statistics. Publication bias was evaluated using the funnel plot asymmetry test. The Newcastle-Ottawa scale (NOS) was used to assess the study quality. Results. A total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR=0.74, 95% CI: 0.55-0.99, I2=97.89%, p<0.00001; adjusted RR=0.76, 95% CI: 0.54–1.07, I2=98.12%, p<0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting. Conclusions. According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.

A Mendelian Randomization Study on Infant Length and Type 2 Diabetes Mellitus Risk

2019 ◽  
Vol 19 (4) ◽  
pp. 224-231 ◽  
Author(s):  
He Zhuang ◽  
Ying Zhang ◽  
Shuo Yang ◽  
Liang Cheng ◽  
Shu-Lin Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Causal Relationship ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Pleiotropic Effect ◽  
Individual Snps

Objective: Infant length (IL) is a positively associated phenotype of type 2 diabetes mellitus (T2DM), but the causal relationship of which is still unclear. Here, we applied a Mendelian randomization (MR) study to explore the causal relationship between IL and T2DM, which has the potential to provide guidance for assessing T2DM activity and T2DM- prevention in young at-risk populations. Materials and Methods: To classify the study, a two-sample MR, using genetic instrumental variables (IVs) to explore the causal effect was applied to test the influence of IL on the risk of T2DM. In this study, MR was carried out on GWAS data using 8 independent IL SNPs as IVs. The pooled odds ratio (OR) of these SNPs was calculated by the inverse-variance weighted method for the assessment of the risk the shorter IL brings to T2DM. Sensitivity validation was conducted to identify the effect of individual SNPs. MR-Egger regression was used to detect pleiotropic bias of IVs. Results: The pooled odds ratio from the IVW method was 1.03 (95% CI 0.89-1.18, P = 0.0785), low intercept was -0.477, P = 0.252, and small fluctuation of ORs ranged from -0.062 ((0.966 - 1.03) / 1.03) to 0.05 ((1.081 - 1.03) / 1.03) in leave-one-out validation. Conclusion: We validated that the shorter IL causes no additional risk to T2DM. The sensitivity analysis and the MR-Egger regression analysis also provided adequate evidence that the above result was not due to any heterogeneity or pleiotropic effect of IVs.

scholarly journals Zinc Intake and Status and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1027 ◽  
Author(s):  
José C. Fernández-Cao ◽  
Marisol Warthon-Medina ◽  
Victoria H. Moran ◽  
Victoria Arija ◽  
Carlos Doepking ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Zinc Concentration ◽  
Meta Analysis ◽  
Plasma Zinc ◽  
Zinc Intake ◽  
Meta Analyses

Zinc could have a protective role against type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aimed to evaluate the association between dietary, supplementary, and total zinc intake, as well as serum/plasma and whole blood zinc concentration, and risk of T2DM. Observational studies, conducted on cases of incident diabetes or T2DM patients and healthy subjects that reported a measure of association between zinc exposure and T2DM, were selected. Random effects meta-analyses were applied to obtain combined results. Stratified meta-analyses and meta-regressions were executed to assess sources of heterogeneity, as well as the impact of covariates on the findings. From 12,136 publications, 16 studies were selected. The odds ratio (OR) for T2DM comparing the highest versus lowest zinc intake from diet was 0.87 (95% CI: 0.78–0.98). Nevertheless, no association between supplementary or total zinc intake from both diet and supplementation, and T2DM was observed. A direct relationship was found between serum/plasma zinc levels and T2DM (OR = 1.64, 95% CI: 1.25–2.14). A moderately high dietary zinc intake, in relation to the Dietary Reference Intake, could reduce by 13% the risk of T2DM, and up to 41% in rural areas. Conversely, elevated serum/plasma zinc concentration was associated with an increased risk of T2DM by 64%, suggesting disturbances in zinc homeostasis.

Systematic Literature Review and Network Meta-analysis (NMA) of SGLT2i as Monotherapy for Type 2 Diabetes Mellitus (T2DM)

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1159-P
Author(s):  
GLENN M. DAVIES ◽  
ANN MARIE MCNEILL ◽  
ELIZA KRUGER ◽  
STACEY L. KOWAL ◽  
FLAVIA EJZYKOWICZ ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Meta Analysis

Plant-based diet and risk of type 2 diabetes mellitus: a systematic review and meta-analysis

2020 ◽  
pp. 1301-1306
Author(s):  
Arwa Aljabali ◽  
Roaa Maghrabi ◽  
Ahmad Shok ◽  
Ghufran Alshawmali ◽  
Abdullah Alqahtani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis

Cinammon (Cinnamomum Spp.) and Type 2 Diabetes Mellitus

2019 ◽  
Vol 18 (3) ◽  
pp. 247-255
Author(s):  
Sierra-Puente D. ◽  
Abadi-Alfie S. ◽  
Arakanchi-Altaled K. ◽  
Bogard-Brondo M. ◽  
García-Lascurain M. ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Key Aspects

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.

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.

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