Common Variants of Homocysteine Metabolism Pathway Genes and Risk of Type 2 Diabetes and Related Traits in Indians

Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variantMTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR=0.78(95% CI=0.67–0.92),P=0.003) and was also associated with 2 h postload plasma glucose (P=0.04), high-density lipoprotein cholesterol (P=0.004), and total cholesterol (P=0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.

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

Current Diabetes Reviews ◽

10.2174/1573399814666171215120228 ◽

2018 ◽

Vol 15 (1) ◽

pp. 31-43 ◽

Cited By ~ 6

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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An Obesity-RelatedFTOVariant and the Risk of Preeclampsia in a Finnish Study Population

Journal of Pregnancy ◽

10.1155/2011/251470 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Miira Klemetti ◽

Leena M. Hiltunen ◽

Sanna Heino ◽

Seppo Heinonen ◽

Eero Kajantie ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Early Onset ◽

Elevated Blood ◽

Study Population ◽

Normotensive Pregnancy ◽

Finnish Study ◽

Risk Of Preeclampsia

Previous studies have demonstrated a common variant of the obesity and fat mass-relatedFTOgene, rs9939609, to be associated with obesity, type 2 diabetes, and elevated blood pressure. We investigated whether theFTOSNP rs9939609 is associated with the risk of preeclampsia (PE) in a Finnish study population. 485 women with prior PE and 449 women who had given birth after a normotensive pregnancy were genotyped (TaqMan) for the SNP rs9939609. The prevalences of genotypes AA, AT, and TT were 15%, 53%, and 32%, respectively, among the PE cases, and 16%, 47%, and 37%, respectively, among the controls (P=0.199). We found no evidence of an association between theFTOSNP rs9939609 and PE. However, our cases were dominated by severe, early-onset PE. Thus, we are unable to exclude an association with the milder, later-onset form of the disease in which the role of maternal metabolic predisposition could be more significant.Erratum to “An Obesity-RelatedFTOVariant and the Risk of Preeclampsia in a Finnish Study Population”

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Effects of Canagliflozin on Fatty Liver Indexes in Patients with Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps29831 ◽

2018 ◽

Vol 21 ◽

pp. 222-235 ◽

Cited By ~ 12

Author(s):

Boyu Li ◽

Ying Wang ◽

Zhikang Ye ◽

Hui Yang ◽

Xiangli Cui ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Liver ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Controlled Trials ◽

Randomized Controlled ◽

Glutamyl Transferase

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) affects about 75% of patients with type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to determine the effect of canagliflozin on fatty liver indexes in T2DM patients. METHODS: A literature search of PubMed, Embase and Cochrane was conducted up to March 30, 2017. The liver function test and lipid profile were extracted from randomized controlled trials (RCTs) to evaluate the effect of canagliflozin on fatty liver. Weighted mean differences (WMDs) or relative risks and 95% confidence intervals (CIs) were computed by using either fixed or random-effects models. Sensitivity analysis and publication bias were evaluated. RESULTS: Our results showed that canagliflozin decreased serum concentrations of alanine amino transferase (WMD: -11.68 [95% CI: -18.95, -10.95]; P<0.001), aspartate amino transferase (WMD: -7.50 [95% CI: -10.61, -4.38]; P<0.001), gamma-glutamyl transferase (WMD: -15.17 [95% CI: -17.73, -12.61]; P<0.001), triglycerides (WMD: -0.10 [95% CI: -0.15, -0.05]; P<0.001) but increased low-density lipoprotein cholesterol (WMD: 0.1 [95% CI: 0.06, 0.13]; P<0.001), high-density lipoprotein cholesterol (WMD: 0.06 [95% CI: 0.05, 0.07]; P<0.001) at week 26 or 52. CONCLUSIONS: Our results indicated that canagliflozin may have a protective effect on fatty liver in T2DM patients. The limitation was that the liver biopsy was hard to obtain in published studies. More RCTs specified on NAFLD are needed to get further information. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Effects of Probiotic Supplementation on Dyslipidemia in Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Foods ◽

10.3390/foods9111540 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1540

Author(s):

Chen Wang ◽

Chengcheng Zhang ◽

Sijia Li ◽

Leilei Yu ◽

Fengwei Tian ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Density Lipoprotein ◽

Controlled Trials ◽

Probiotic Supplementation ◽

Randomized Controlled

The effectiveness of probiotic consumption in controlling dyslipidemia in type 2 diabetes mellitus (T2DM) has been unclear. We reviewed relevant randomized controlled trials (RCTs) to clarify the effect of probiotic intake on dyslipidemia in T2DM patients. The Web of Science, Scopus, PubMed and Cochrane Library databases were used for searching relevant RCTs published up to October 2020. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations were selected as the primary indicators for dyslipidemia. The results of 13 eligible RCTs showed that probiotic intake could significantly reduce TC (SMD: −0.23, 95% CI: (−0.37, −0.10)) and TG (SMD: −0.27, 95% CI: (−0.44, −0.11)) levels, but did not regulate LDL-C or HDL-C concentrations. Subgroup analysis showed that multispecies probiotics (≥two species), but not single-species probiotics, significantly decreased TC and TG concentrations. Furthermore, powder, but not liquid, probiotics could reduce TC and TG concentrations. This meta-analysis demonstrated that probiotic supplementation is helpful in reducing TC and TG concentrations in T2DM patients. However, more well-controlled trials are needed to clarify the benefits of probiotics on dyslipidemia in T2DM patients.

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Association of miR-146a polymorphism rs2910164 and type 2 diabetes risk: a meta-analysis

Journal of International Medical Research ◽

10.1177/0300060520931313 ◽

2020 ◽

Vol 48 (8) ◽

pp. 030006052093131

Author(s):

Liqing Cheng ◽

Min Zhou ◽

Dongmei Zhang ◽

Bing Chen

Keyword(s):

Type 2 Diabetes ◽

Gene Polymorphisms ◽

Disease Duration ◽

Genetic Model ◽

Meta Analysis ◽

Confounding Factors ◽

Dominant Model ◽

Subgroup Analyses

Objective Circulating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D. Methods PubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities. Results Four studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887–2.541), 1.102 (0.931–1.304), 1.276 (0.900–1.811), 1.204 (0.878–1.652), 1.238 (0.880–1.740), and 1.350 (0.904–2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model. Conclusions Our findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.

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The Role of Aerobic Training Variables Progression on Glycemic Control of Patients with Type 2 Diabetes: a Systematic Review with Meta-analysis

Sports Medicine - Open ◽

10.1186/s40798-019-0194-z ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 2

Author(s):

Rodrigo Sudatti Delevatti ◽

Cláudia Gomes Bracht ◽

Salime Donida Chedid Lisboa ◽

Rochelle Rocha Costa ◽

Elisa Corrêa Marson ◽

...

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Glycemic Control ◽

Aerobic Training ◽

Meta Analysis

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

European Heart Journal ◽

10.1093/eurheartj/ehz748.0812 ◽

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.

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