Decreased Risk Of Type 2 Diabetes Mellitus Research Articles

Association between the MCP-1 -2518 A > G (rs1024611) polymorphism and susceptibility to type 2 diabetes mellitus and diabetic nephropathy: a meta-analysis

BackgroundStudies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk.MethodsEligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger’s test.ResultsIn total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66–0.93, P = 0.006; PQ = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11–1.71, P = 0.004, PQ = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041).ConclusionThe MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study

BackgroundObservational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two.MethodsTwo-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM.ResultsUnivariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10–5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2.ConclusionsThis study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

The protective effects of lipoxin A4 on type 2 diabetes mellitus: A Chinese prospective cohort study.

Several cellular and animal studies have suggested that lipoxin A4 (LXA4) has a protective effect on type 2 diabetes mellitus (T2DM) development. However, little is known about whether LXA4 influences T2DM development at the population level. We included 2755 non-diabetic participants from a cohort study in China who were followed for about seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association between LXA4 and incident T2DM. Mediation models were used to examine how serum lipids as mediators impact the association between LXA4 and T2DM. In total, 172 newly diagnosed T2DM cases were identified. Multivariate-adjusted HR for T2DM in the fourth compared with the first quartile of LXA4 was 0.62 (95% CI: 0.40-0.96). When used the optimal cutoff value determined by the receiver operating characteristic curve, the results showed participants with LXA4 > 2.84 ng/mL had a decreased T2DM risk compared to those with LXA4 ≤ 2.84 ng/mL (HR: 0.63, 95% CI: 0.45-0.89). The effect of LXA4 on incident T2DM was significantly modified by gender (P -interaction = 0.024) and family history of diabetes (P -interaction = 0.025). Additionally, the association between LXA4 and incident T2DM was partially suppressed by the TyG and TG/HDL-c ratio, with a suppression proportion of 22.2% and 16.0%, respectively. Higher LXA4 levels are significantly associated with a lower risk of T2DM development. The present findings would be helpful in understanding the effect of LXA4 on T2DM development at the population level.

The Correlation of Nrf2 rs6721961 Variants with the Risk of Type 2 Diabetes Mellitus and Obesity in Kurdistan of Iraq

Background: Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disease that the interaction of genetic background with environmental factors could enhance its risk. The nuclear erythroid-2-related factor 2 (Nrf2) protects cells against oxidative damage and toxicity. Objectives: This study aimed to determine the possible correlation between the Nrf2 gene variants with the risk of T2DM and obesity in the Kurdistan of Iraq. Methods: This study was conducted on 250 individuals categorized into 4 groups: 67 obese T2DM patients (body mass index (BMI) ≥ 30 kg/m2), 65 normal BMI diabetic patients (BMI < 25 kg/m2), 62 obese non-diabetics, and 56 normal BMI non-diabetic individuals. The Nrf2 rs6721961 variants were identified by polymerase chain reaction (PCR) technique followed by digestion with the restriction enzyme of NgoMIV. Results: In the obese T2DM group, the levels of waist, and wrist circumference were significantly more than those of obese non-diabetic controls. Total antioxidant capacity level was not significantly different comparing patients with their controls. The Nrf2 T allele significantly decreased the risk of T2DM in normal BMI patients. In addition, carrying the T allele significantly reduced the risk of obesity. Conclusions: According to the results, significantly higher levels of anthropometric parameters was detected in obese T2DM compared with obese non-diabetic controls. The T allele of Nrf2 decreased T2DM risk among patients with normal BMI and obesity risk among Kurdish residents of Iraq. The findings of our research can be used in the prevention and management of T2DM by improving lifestyle habits.

Association of CYP7A1 and CYP2E1 Polymorphisms with Type 2 Diabetes in the Chinese Han Populations.

BackgroundType 2 diabetes mellitus (T2DM) is caused by diverse environmental and genetic risk factors. Previous studies have reported that cytochrome P450 (CYP) is a promising gene for T2DM. Therefore, we aimed to determine the effects of CYP7A1 and CYP2E1 polymorphisms on T2DM susceptibility among the Chinese Han population.MethodsA case-control study was conducted to assess the potential relationship of four polymorphisms (rs8192879, rs12542233, rs2070672 and rs2515641) with T2DM susceptibility in the Chinese population, involving 512 T2DM patients and 515 age- and gender-matched healthy individuals. We used the Agena MassARRAY platform to detect CYP7A1 and CYP2E1 polymorphisms. The relationship between genetic polymorphisms and T2DM risk was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models.ResultsAfter adjusting for age and gender, rs12542233 in the CYP7A1 gene was significantly associated with decreased T2DM risk (recessive: OR = 0.67, 95% CI = 0.49–0.91, p = 0.012; after FDR correction, p = 0.048). The CYP7A1 rs12542233 was associated with a reduced risk of T2DM in people over 59 years of age (p = 0.010). In the population with BMI ≤ 24 kg/m2, CYP7A1 rs12542233 was associated with an increased risk of T2DM (p < 0.05). In the population with BMI > 24 kg/m2, CYP2E1 rs2515641 can significantly reduce the risk of T2DM (p < 0.05). And rs8192879, rs2070672 and rs2515641 could significantly increase the risk of diabetes retinopathy in T2DM patients (p < 0.05). Furthermore, the Trs8192879Crs12542233 haplotype was significantly associated with T2DM (p = 0.019).ConclusionCYP7A1 and CYP2E1 polymorphisms may contribute to T2DM susceptibility in the Chinese Han population, especially in stratified analysis.

Evaluation of association studies and a systematic review and meta-analysis of VDR polymorphisms in type 2 diabetes mellitus risk.

Numerous original studies and 4 published meta-analyses have reported the association between the Vitamin D receptor (VDR) BsmI, FokI, ApaI, and TaqI polymorphisms and type 2 diabetes mellitus (T2DM) risk. However, the results were inconsistent. Therefore, an updated meta-analysis was performed to further explore these issues.To further explore the association between the VDR BsmI, FokI, ApaI, and TaqI polymorphisms and T2DM risk.PubMed, EMBASE, Scopus, and Wanfang databases were searched. The following search strategy were used: (VDR OR vitamin D receptor) AND (polymorphism OR variant OR mutation) AND (diabetes OR mellitus OR diabetes mellitus). Pooled crude odds ratios with 95% confidence intervals were applied to evaluate the strength of association in 5 genetic models. Statistical heterogeneity, the test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 12.0). To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) and Bayesian false discovery probability (BFDP) test.Overall, the VDR BsmI polymorphism was associated with a significantly decreased T2DM risk in Asians; the VDR FokI polymorphism was associated with a significantly decreased T2DM risk in Asians, African countries, and Asian countries; the VDR ApaI polymorphism was associated with a significantly decreased T2DM risk in Caucasians and North American countries.On the VDR ApaI polymorphism, a significantly increased T2DM risk was found in a mixed population. However, when we further performed a sensitivity analysis, FPRP, and BFDP test, less-credible positive results were identified (all FPRP > 0.2 and BFDP > 0.8) in any significant association.In summary, this study strongly indicates that all significant associations were less credible positive results, rather than from true associations.

Co-exposure of serum calcium, selenium and vanadium is nonlinearly associated with increased risk of type 2 diabetes mellitus in a Chinese population

BackgroundMetals play an important role in type 2 diabetes mellitus (T2DM). This study aimed to explore the association of T2DM risk with single metal exposure and multi-metal co-exposure. MethodsA case-control study with 223 T2DM patients and 302 controls was conducted. Serum concentrations of 19 metals were determined by inductively coupled plasma mass spectrometry (ICP-MS). Those metals with greater effects were screened out and co-exposure effects of metals were assessed by least absolute shrinkage and selection operator (LASSO) regression. ResultsSerum calcium (Ca), selenium (Se) and vanadium (V) were found with greater effects. Higher levels of Ca and Se were associated with increased T2DM risk (OR = 2.23, 95%CI: 1.38–3.62, Ptrend = 0.002; OR = 3.16, 95%CI: 1.82–5.50, Ptrend < 0.001), but higher V level was associated with decreased T2DM risk (OR = 0.58, 95%CI: 0.34–0.97, Ptrend < 0.001). Serum Ca and V concentrations were nonlinearly associated with T2DM risk (Poverall < 0.001, Pnonliearity < 0.001); however, Se concentration was linearly associated with T2DM risk (Poverall < 0.001, Pnonliearity = 0.389). High co-exposure score of serum Ca, Se and V was associated with increased T2DM risk (OR = 3.50, 95%CI: 2.08–5.89, Ptrend < 0.001) as a non-linear relationship (Poverall < 0.001, Pnonliearity = 0.003). ConclusionsThis study suggest that higher levels of serum Ca and Se were associated with increased T2DM risk, but higher serum V level was associated with decreased T2DM risk. Moreover, co-exposure of serum Ca, Se and V was nonlinearly associated with T2DM risk, and high co-exposure score was positively associated with T2DM risk.

Association between intercellular adhesion molecule 1 (ICAM1) polymorphisms and diabetic foot susceptibility

The objective of the present study was to explore the association between intercellular adhesion molecule 1 (ICAM1) polymorphisms (rs5498 and rs3093030) and diabetic foot (DF) susceptibility in a Chinese Han population.128 type 2 diabetes mellitus (T2DM) patients with DF, 147 T2DM patients without DF, and 155 healthy individuals were enrolled in this study. ICAM1 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotypes and alleles of the polymorphisms were compared by χ test between the 2 groups. Association between ICAM1 polymorphisms and DF susceptibility was expressed through odds ratio (OR) with corresponding 95% confidence interval (95%CI). Effects of ICAM1 polymorphisms on DF clinical characteristics were analyzed by t test.GG genotype of rs5498 polymorphism was distinctly correlated with decreased T2DM risk (OR = 0.369, 95%CI = 0.152-0.895) and reduced susceptibility to DF among healthy controls (OR = 0.316, 95%CI = 0.119-0.837). Similar results were discovered between rs5498 G allele and decreased risk of T2DM (OR = 0.676, 95%CI = 0.475-0.963) and DF (OR = 0.656, 95%CI = 0.453-0.950) among healthy controls. Individuals carrying rs3093030 T allele had low susceptibility to DF developed from T2DM (OR = 0.634, 95%CI = 0.412-0.974). DF patients carrying rs5498 AA genotype had significantly higher serum creatinine levels than GG genotype carriers (P = .003).ICAM1 rs3093030 polymorphism may act as a protective factor against DF developed from T2DM, moreover, rs5498 may be involved in onset of T2DM.Clinical trial number: ChiCTR-INR-18010231.

Association between RBMS1 gene rs7593730 and BCAR1 gene rs7202877 and Type 2 diabetes mellitus in the Chinese Han population.

Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 are related to type 2 diabetes. However, the association of these loci with type 2 diabetes mellitus (T2DM) has not been examined in Chinese. We performed a replication study to investigate the association of the 2 susceptibility loci with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991 with T2DM and 970 controls) for each of the 2 single nucleotide polymorphisms (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined their association with T2DM using logistic regression analysis. We also analyzed the correlation of the SNP alleles and clinical phenotypes. In additive model, genotype association analysis of BCAR1 rs7202877 loci revealed that the homozygous of rs7202877 GG carriers had significantly decreased T2DM risk compared to homozygous carriers of TT (P=0.038, OR 0.44, 95% CI 0.20-0.96). In the recessive model, the GG genotype GG had significantly decreased T2DM risk compared to GT+TT (P=0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C (mmol/L) (P=0.007). As for rs7593730, the carriers of CT and TT genotype had significantly decreased T2DM risk compared to the carriers of CC genotype (CT: CC P=0.038, OR 0.71, 95% CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95% CI 0.13-0.76). In a dominant model, TT+CT: CC (P=0.013, OR 0.673, 95% CI 0.49-0.92) and in a recessive model, TT: CT+CC (P=0.019, OR 0.59, 95% CI 0.39-0.92). The T allele carriers had significantly decreased T2DM risk compared to the carriers of C (P=0.002, OR 0.65, 95% CI 0.50-0.86). Allele T was statistically correlated with FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the Chinese population.

Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, praw<0.001, pFDR<0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk.

The association of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus in European, American, and African populations: a meta-analysis

Introduction: Several studies regarding the association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus (T2DM) showed inconsistent results. This study aimed to investigate the association of ENPP1 K121Q gene polymorphism with T2DM risk using meta-analysis. The study was limited to the American, European, and African populations.Methods: PubMed and Embase databases were searched for eligible publications. The following information was extracted from each study: name of first author, publication year, country of origin, sample size of cases and controls, and size of each allele. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between ENPP1 K121Q gene polymorphism and T2DM risk were assessed using random or fixed effect model. A comprehensive meta-analysis (CMA) 2.0 was used to analyze the data.Results: Nineteen studies (17717 cases/28022 controls) on the association between ENPP1 K121Q gene polymorphism and T2DM risk were included in this meta-analysis. The results indicated that the ENPP1 K121Q gene polymorphism was associated with increased T2DM risk (Q vs. K genetic model, OR 95% CI = 1.11 [1.02–1.22], p = 0.014; QQ vs. KK + KQ, OR 95% CI = 1.14 [1.01–1.23], p = 0.039) and decreased T2DM risk (K vs. Q, OR 95% CI = 0.90 [0.82–1.00], p = 0.014; KK vs. KQ + QQ, OR 95% CI = 0.89 [0.80–0.98], p = 0.024).Conclusions: The results indicate that the ENPP1 K121Q gene polymorphism is associated with the risk of T2DM in the American, European, and African populations.

Tea consumption and risk of type 2 diabetes mellitus: a systematic review and meta-analysis update

ObjectiveTea has been suggested to decrease blood glucose levels and protect pancreatic β cells in diabetic mice. However, human epidemiological studies showed inconsistent results for the association between tea consumption...

English

&nbsp; Polymorphism in Renin-Angiotensin-Aldosterone System (RAAS) genes have been studied extensively in various ethnic groups and largely with inconsistent findings on relationship with the risk of developing type 2 diabetes mellitus (T2DM). In this study, we investigated the association of Insertion/Deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) and -344 C/T polymorphism of aldosterone synthase [cytochrome P450 (CYP11B2)] with T2DM in an Emirati population and&nbsp;interactive effects between these two gene polymorphisms on T2DM risk.&nbsp;A total of 243 Emirati subjects (133 healthy control and 110 T2DM patients) were selected for the study. The ACE genotypes were determined by polymerase chain reaction (PCR) followed by agarose gel electrophoresis. The CYP11B2 genotyping was performed by PCR-&nbsp;Restriction Fragment Length Polymorphism Analysis(RFLP).&nbsp;ACE genotypes were not associated with T2DM&nbsp;risk.&nbsp;The frequencies of D allele were 0.68 and 0.64 in the patients and healthy group respectively and the differences were not statistically significant. For CYP11B2 -344C/T polymorphism, CC genotype was found significantly higher in healthy subjects than in T2DM patients (22.1 Vs 9.8%, p=0.016). The subjects with CC genotype were at decreased T2DM risk in the recessive model [Odd ratio 0.38 (0.17-0.84)]. &nbsp;An interactive effect on T2DM risk was found between ACE-ID and CYP11B2 -CC genotypes.&nbsp;In the subjects with combination of ID + CC genotypes, risk of T2DM was further reduced (odd ratio 0.05 vs 1.12). The association of CC with T2DM was independent of age and gender. To date, this study is the first report on association of CYP11B2 -344C/T with T2DM and its possible interaction with ACE I/D polymorphism in an Emirati population. The results suggest that ACE I/D polymorphism does not affect T2DM risk independently however, subjects with CC genotypes either alone or in combination with ACE &nbsp;I/D heterozygote would be at decreased risk of developing T2DM. &nbsp; Key words: &nbsp;Type 2 diabetes mellitus, CYP11B2, Renin-Angiotensin-Aldosterone System, angiotensin converting enzyme, genetic polymorphism

Prospective Evaluation of B-type Natriuretic Peptide Concentrations and the Risk of Type 2 Diabetes in Women

Animal data suggest that natriuretic peptides play an important role in energy metabolism, but prospective studies evaluating a relationship between these peptides and type 2 diabetes mellitus (T2DM) in humans are few and results are conflicting. We used a prospective case-cohort approach (n = 491 T2DM cases, n = 561 reference subcohort) within the Women's Health Study to evaluate baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and the risk of incident T2DM. We also tested for associations between 4 common variants in the natriuretic peptide A and B genes (NPPA and NPPB) and NT-proBNP concentrations (n = 458) and incident T2DM (n = 1372 cases among 22 607 women). Case subjects had higher median baseline body mass index (29.4 vs 25.0 kg/m(2), P < 0.001) and lower baseline median (interquartile range) NT-proBNP concentrations [46.8 ng/L (26.1-83.2) vs 66.7 ng/L (39.3-124.7), P < 0.001]. In proportional hazards models adjusting for established diabetes risk factors, women in the highest quartile of baseline NT-proBNP concentration (≥ 117.4 ng/L) had a 49% reduction in risk of T2DM [hazard ratio (HR) 0.51, 0.30-0.86, P = 0.01] relative to those in the lowest quartile. Two of the 4 tested variants in NPPA and NPPB (rs632793, rs198389) were associated with increased NT-proBNP concentrations and reduced risk of T2DM. For example, each copy of the minor allele of rs632793 was associated with increased NT-proBNP [β (SE) = 0.201 (0.063), P < 0.01] and decreased T2DM risk (HR 0.91, 0.84-0.989, P = 0.026). NT-proBNP concentrations that are high, but still within the reference interval, associate with reduced risk of incident diabetes in women and support a favorable role for natriuretic peptides in the prevention of T2DM.