Risk Of To Type 2 Diabetes Mellitus Research Articles

Potential Association of The Pathogenic Kruppel-like Factor 14 (KLF14) and Adiponectin (ADIPOQ) SNVs with Susceptibility to T2DM.

To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM. To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population. We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included. Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively. We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing.

Haplotype analysis on association between C-reactive protein gene and susceptibility to type 2 diabetes mellitus in Chinese Han population : CRP gene and type 2 diabetes mellitus.

We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis. A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, allinteraction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047. Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

Fermented dietary fiber from soy sauce residue exerts antidiabetic effects through regulating the PI3K/AKT signaling pathway and gut microbiota-SCFAs-GPRs axis in type 2 diabetic mellitus mice

The gut plays a crucial role in the development and progression of metabolic disorders, particularly in relation to type 2 diabetes mellitus (T2DM). While a high intake of dietary fiber is inversely associated with the risk of T2DM, the specific effects of various dietary fibers on T2DM are not fully understood. This study investigated the anti-diabetic properties of fermented dietary fiber (FDF) derived from soy sauce residue in T2DM mice, demonstrating its ability to lower blood glucose levels and ameliorate insulin resistance. Our findings revealed that FDF could enhance hepatic glucose metabolism via the IRS-1/PI3K/AKT/mTOR pathway. Additionally, the anti-diabetic effect of FDF was correlated with alterations in gut microbiota composition in T2DM mice, promoting a healthier gut environment. Specifically, FDF increased the abundance of beneficial flora such as Dubosiella, Butyricimonas, Lachnospiraceae_NK4A136_group, Lactobacillus and Osillibacter, while reducing harmful bacteria including Bilophila, Parabacteroides and Enterorhabdus. Further analysis of microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs), provided evidence of FDF's regulatory effects on cecal contents in T2DM mice. Importantly, FDF treatment significantly restored the G-protein-coupled receptors (GPRs) expression in the colon of T2DM mice. In conclusion, our study suggests that the anti-diabetic effects of FDF are associated with the regulation of both the liver-gut axis and the gut microbiota-SCFAs-GPRs axis.

Association between vitamin D levels and insulin resistance in patients with type 2 diabetes mellitus

Background: Insulin resistance (IR) is a major contributor to type 2 diabetes mellitus (T2DM) and is associated with various metabolic disorders. Vitamin D deficiency (VDD) has been linked to an increased risk of T2DM, but the relationship between vitamin D status and IR in T2DM patients remains unclear. This study explores this association in a male population with T2DM in Baghdad, Iraq.Methods: A case-control study was conducted on 190 male participants: 40 healthy controls and 150 patients categorized into different groups; 40 diabetic patients, 55 with coronary artery disease (CAD) and T2DM (CAD+DM), and 55 with only CAD. Physicians diagnosed them, and they were evaluated by physical and full medical history. All the sample set parameters were measured in the fasting state for each group. The biochemical tests included body mass index (BMI), vitamin D levels, insulin levels, fasting tests glucose (FBG), and HbA1c were measured. Insulin resistance was calculated using the HOMA-IR model.Results: Vitamin D levels were significantly lower in all diabetic groups (DM, CAD+DM) compared to the control group (p<0.001). All diabetic patients had insulin resistance. BMI was significantly higher in the CAD and CAD+DM groups compared to controls (p<0.00001, p<0.004). FBG, HbA1c, insulin levels, and HOMA-IR were all significantly higher in diabetic patients compared to controls (p<0.001 for all). Furthermore, increased HbA1c, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were associated with CAD progression in T2DM patients (p < 0.001).Conclusion: This study suggests that vitamin D deficiency may contribute to insulin resistance in male T2DM patients in Baghdad, Iraq. Maintaining optimal vitamin D levels may be beneficial in diabetes management in this population. Incorporating vitamin D screening into routine check-ups for T2DM patients could aid in early detection and prevention of insulin resistance-associated complications.Keywords: Diabetes mellitus; Insulin resistance; Vitamin D; Coronary artery disease

The role of small dense LDL-C/large buoyant LDL-C ratio as an independent risk factor in patients with type 2 diabetes mellitus and metabolic syndrome

Dyslipidemia plays a key role in metabolic syndrome (MS), intricately linked to type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences in low-density lipoprotein cholesterol (LDL-C) subfraction levels between T2DM and T2DM with MS, and identify the risk factors associated with the disease. A total of 246 individuals diagnosed with T2DM, including 144 T2DM patients with MS, and 147 healthy subjects were recruited. All participants underwent a comprehensive clinical evaluation. Lipoprotein subfraction analysis was performed using the Lipoprint LDL system. Multivariate logistic regression analysis revealed that several lipid markers, including triglyceride (TG), LDL-C, large buoyant LDL-C (lbLDL-C), small dense LDL-C (sdLDL-C), LDLC2-5, and sdLDL-C/lbLDL-C ratio, were identified as independent risk factors for T2DM. Additionally, TG, sdLDL-C, LDLC-4, LDLC-5, and sdLDL-C/lbLDL-C ratio were found to be independent risk factors for T2DM with MS. Furthermore, the results of the receiver operating characteristic (ROC) curves demonstrated that sdLDL-C, LDLC-4, LDLC-3, and sdLDL-C/lbLDL-C ratio exhibited excellent predictive performance for the risk of T2DM (AUC >0.9). The sdLDL-C/lbLDL-C ratio emerges as a shared independent risk factor for T2DM and MS complications. Furthermore, sdLDL-C/lbLDL-C ratio, along with LDL-4 and LDL-3, exhibits noteworthy predictive capabilities for T2DM.

Menopausal Hormone Therapy in Women with Type 2 Diabetes Mellitus: An Updated Review.

Menopause is accompanied by several metabolic adaptations, which are related to insulin resistance, increased total body fat mass, and central abdominal fat accumulation, predisposing women to type 2 diabetes mellitus (T2DM) development. Metabolic syndrome has a high prevalence in postmenopausal women, indicating the loss of estrogen protection on metabolic and cardiovascular health. Moreover, earlier age at menopause has been related to increased risk of T2DM. Menopausal hormone therapy (MHT) has favorable results in glucose metabolism. Indeed, it reduces the risk of T2DM in women without this condition and improves glycemic control in women with T2DM. Before MHT initiation in women with clinical indications, it is imperative to assess their cardiovascular disease (CVD) risk, using official electronic algorithms for score calculation. The latter will determine regimen, dose, and administration route of MHT. Oral estrogens are preferable in women with low CVD risk, while transdermal administration is indicated in those with moderate and high CVD risk, as the risk of stroke and venous thromboembolism (VTE) is increased with oral administration. Oral 17β-estradiol is usually preferred in women with T2DM, as this route has more beneficial effects on glucose metabolism. Oral estrogens are also suggested in perimenopausal or recently postmenopausal women with low CVD risk. Although oral estrogens have favorable effects when indicated, the risk of VTE or stroke should always be considered. Micronized progesterone, dydrogesterone, and transdermal norethisterone are the progestogens used in postmenopausal women with T2DM and intact uterus. MHT should not be initiated in women > 60years or > 10years in menopause, as there is an increased thromboembolic risk in women with established atherosclerosis and no additional cardiovascular benefit in women without atherosclerosis. In conclusion, MHT administration in postmenopausal women with T2DM can be safe and effective as long as the therapeutic regimen has been properly selected according to their cardiovascular, metabolic, and fracture risk.

Predictive value of triglycerides to high-density lipoprotein cholesterol and triglyceride glycemic index for diabetes incidence in pre-diabetes patients: a prospective cohort study

BackgroundThe triglyceride glucose (TyG) and triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-c) are the indices that can predict the progression of pre-diabetes to type 2 diabetes mellitus (T2DM). This study aimed to examine the relationship between TyG and TG/HDL-c indices with the incidence of T2DM in pre-diabetes patients.MethodsA total of 758 pre-diabetic patients aged 35–70 years who were enrolled in a prospective Fasa Persian Adult Cohort were followed up for 60 months. TyG and TG/HDL-C indices were obtained at baseline data and divided into quartiles. The 5-year cumulative incidence of T2DM was analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates.ResultsDuring 5 years of follow-up, there were 95 incident cases of T2DM, with an overall incidence rate of 12.53%. After adjusting for age, sex, smoking, marital status, socioeconomic status, body mass index, waist circumference, hip circumference, hypertension, total cholesterol, and dyslipidemia, the multivariate-adjusted hazard ratios (HRs) demonstrated that patients with the highest TyG and TG/HDL-C indices quartile were at higher risk of T2DM (HR = 4.42, 95%CI 1.75–11.21) and (HR = 2.15, 95%CI 1.04–4.47), respectively, compared to participants in the lowest quartile. As the quantiles of these indices increase, the HR value shows a significant increment (P < 0.05).ConclusionThe results of our study showed that the TyG and TG/HDL-C indices can be important independent predictors for the progression of pre-diabetes to T2DM. Therefore, controlling the components of these indicators in pre-diabetes patients can prevent developing T2DM or delay its occurrence.

The role of single-nucleotide polymorphisms of some candidate genes of carbohydrate and fat metabolism in predicting the risk of type 2 diabetes mellitus

Over the past decade, some progress has been made in identifying and characterizing variants of DNA polymorphisms of genes associated with predisposition to type 2 diabetes mellitus (T2DM). The analysis of gene polymorphisms in combination with socio-demographic, clinical and metabolic parameters can be considered as a promising approach to identify high-risk groups for the development of T2DM. The review includes foreign and domestic studies of predictive models for the risk of developing T2DM comprising single-nucleotide polymorphisms, published in the period from 2006 to 2021. The search for the literature sources was carried out on the PubMed platform. The predictive accuracy of polygenic risk scores was assessed by comparing the area under the curve (AUC). The most commonly used clinical predictors of T2DM risk are sex, age, BMI, family history of diabetes, presence of arterial hypertension, waist circumference, waist-to-hip ratio. All genetic risk models for T2DM had lower AUC values than phenotypic (clinical) risk models. The addition of genetic factors has, in turn, improved AUC compared to purely clinical risk models in many studies, which may be a useful tool for primary prevention of T2DM. However, only those polymorphisms that strongly confirm their association with the risk of developing T2DM in different populations studies should be added to predictive risk scales.

Gut microbial indicators of metabolic health underlie age-related differences in obesity and diabetes risk among Native Hawaiians and Pacific Islanders.

Native Hawaiians and Pacific Islanders (NHPIs) suffer from higher prevalence of and mortality to type 2 diabetes mellitus (T2DM) than any other major race/ethnic group in Hawaii. Health inequities in this indigenous population was further exacerbated by the SARS-CoV-2 pandemic. T2DM progression and medical complications exacerbated by COVID-19 are partially regulated by the gut microbiome. However, there is limited understanding of the role of gut bacteria in the context of inflammation-related diseases of health disparities including T2DM and obesity. To address these gaps, we used a community-based research approach from a cohort enriched with NHPI residents on the island of Oahu, Hawaii (N=138). Gut microbiome profiling was achieved via 16s rDNA metagenomic sequencing analysis from stool DNA. Gut bacterial capacity for butyrate-kinase (BUK)-mediated fiber metabolism was assessed using quantitative PCR to measure the abundance of BUK DNA and RNA relative to total bacterial load per stool sample. In our cohort, age positively correlated with hemoglobin A1c (%; R=0.39; P<0.001) and body mass index (BMI; R=0.28; P<0.001). The relative abundance of major gut bacterial phyla significantly varied across age groups, including Bacteroidetes (P<0.001), Actinobacteria (P=0.007), and Proteobacteria (P=0.008). A1c was negatively correlated with the relative levels of BUK DNA copy number (R=-0.17; P=0.071) and gene expression (R=-0.33; P=0.003). Interestingly, we identified specific genera of gut bacteria potentially mediating the effects of diet on metabolic health in this cohort. Additionally, α-diversity among gut bacterial genera significantly varied across T2DM and BMI categories. Together, these results provide insight into age-related differences in gut bacteria that may influence T2DM and obesity in NHPIs. Furthermore, we observed overlapping patterns between gut bacteria and T2DM risk factors, indicating more nuanced, interdependent interactions among these factors as partial determinants of health outcomes. This study adds to the paucity of NHPI-specific data to further elucidate the biological characteristics associated with pre-existing health inequities in this racial/ethnic group that is significantly underrepresented in biomedical research.

Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: Systematic review and meta-analysis.

BackgroundTo estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria.MethodsSystematic review and meta-analysis were conducted by searching Medline, Embase, and Cochrane between January 1, 2010 and December 31, 2021 for observational studies investigating progression to T2DM after GDM. Inclusion criteria were IADPSG-diagnosed GDM, studies with both GDM and controls, postpartum follow-up duration at least one year. Data were pooled by random effects meta-analysis models. Heterogeneity was assessed by I2 statistic. The pooled relative risk for incidence of T2DM and pre-diabetes between GDM participants and controls were estimated. Reasons for heterogeneity among studies were investigated by prespecified subgroup and meta-regression analysis. Publication bias was assessed by the Begg’s and Egger’s tests.ResultsThis meta-analysis of six studies assessed a total of 61932 individuals (21978 women with GDM and 39954 controls). Women with IADPSG-diagnosed GDM were 6.43 times (RR=6.43, 95% CI:3.45-11.96) more likely to develop T2DM in the future compared with controls. For GDM women, the cumulative incidence of T2DM was 12.1% (95% CI: 6.9%-17.3%), while the pooled cumulative incidence of T2DM was estimated to be 8% (95% CI: 5-11%) in studies with 1 to 5 years of follow-up and increased to 19% (95% CI: 3-34%) for studies with more than 5 years of follow-up. Women with IADPSG-diagnosed GDM had 3.69 times (RR=3.69, 95% CI:2.70-5.06) higher risk of developing pre-diabetes (including impaired fasting glucose and/or impaired glucose tolerance) than controls. Meta-regression analysis showed that the study effect size was not significantly associated with study design, race, length of follow-up, and maternal age (P>0.05). Overall, the studies had a relatively low risk of bias.ConclusionsWomen with IADPSG-diagnosed GDM have higher risk of developing T2DM and pre-diabetes. The risk of T2DM in GDM women are higher with longer follow-up duration. Our results highlight the importance of promoting postpartum screening and keeping health lifestyle as well as pharmacological interventions to delay/prevent the onset of T2DM/pre-diabetes in GDM women.Systematic review registration https://www.crd.york.ac.uk/prospero, identifier (CRD42022314776)

Relationships of ABO and Rhesus blood groups with type 2 diabetes mellitus: a systematic review and meta-analysis.

ObjectivesThe susceptibility to type 2 diabetes mellitus (T2DM) has been linked to blood type. We aimed to characterize the relationships of the ABO and Rhesus blood groups with T2DM.MethodsLiterature searches were performed using the Medline, PubMed, Scopus, Cochrane, EMBASE, and Google Scholar databases to identify studies published up to 31 March 2022. The PRISMA guidelines were used for reporting. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using fixed-effects models.ResultsTwenty-six studies of 6870 patients with T2DM and 11,879 controls were identified. Compared with the other ABO groups, people with blood type B were at higher risk of T2DM (OR: 1.30, 95% CI: 1.20–1.41), while group O was associated with a lower risk (OR: 0.92, 95% CI: 0.86–0.98). There were no significant associations of T2DM with blood types A or AB, or Rh factor.ConclusionIndividuals with blood type B are at higher risk of developing T2DM. Therefore, they should be screened for T2DM on a frequent basis and be made aware of the importance of maintaining a balanced diet and regular exercise for the prevention of obesity and T2DM.PROSPERO registration numberCRD42022353945.

Genetic variations of tumor necrosis factor-α and prostaglandin-endoperoxide synthase 2 genes among Egyptian patients with type 2 diabetes mellitus and diabetic nephropathy

ObjectivesThe current study aimed to determine whether genetic differences in the tumor necrosis factor-α (TNF-α) and prostaglandin-endoperoxide synthase 2 (PTG2) genes are linked to type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). BackgroundDN is a major cause of chronic kidney disease (CKD). Unfortunately, the precise pathogenic mechanisms of DN are not completely understood. Recent data suggest a link between inflammatory cytokines and the chronic complications of T2DM. TNF-α and PTG2 are key mediators of inflammation. Subjects and methodsThis is a case-control study that includes 100 patients (group 1: 50 diabetic patients with diabetic nephropathy and group 2: 50 patients without diabetic nephropathy) and 50 age- and sex-matched healthy controls (group 3). Genotyping of TNF-α (rs3651525) and PTGS2 (rs689466) by real-time PCR was applied. ResultsTNF-α (rs3651525) and PTGS2 (rs689466) genotype frequency and allelic distribution are in Hardy-Weinberg equilibrium (HWE). When T2DM patients with nephropathy were compared to those without DN, regression analysis for the PTGS2 rs689466 and TNF-rs361525 single nucleotide polymorphisms (SNPs) demonstrated that none of the SNP genotypes showed a major risk factor for DN susceptibility. As regards TNF-α rs361525, GA and AA genotypes were significantly associated with a higher risk of T2DM when compared to GG, and A allele showed a 3.721-fold increased risk.TNF-α rs361525 AA genotype (OR, 10.980; 95% CI 1.385–87.066) and TNF-rs361525 GA genotype (OR, 3.050; 95% CI 1.315–7.0758) are the most substantially linked parameters with the risk of diabetes mellitus in univariate analysis.According to the multivariate analysis, the AA and GA genotypes of the SNP rs361525 significantly affect the development of diabetes mellitus. No remarkable association was found between the PTGS2 (rs689466) polymorphism and diabetes mellitus and diabetic nephropathy. ConclusionIn contrast to the lack of a significant correlation between PTGS2 (rs689466) and DM or DN, TNF-α rs361525 was connected to the possibility of developing diabetes mellitus in our study.

Association analysis of SOCS3, JAK2 and STAT3 gene polymorphisms and genetic susceptibility to type 2 diabetes mellitus in Chinese population

AimThe association of polymorphisms in the three genes of SOCS3, JAK2 and STAT3 with genetic susceptibility to type 2 diabetes mellitus (T2DM) was explored, and its interaction with environmental factors such as hypertension and triglycerides was analyzed.MethodsThe Hardy–Weinberg balance test was used to analyze the random balance of genes in the population. The analysis of the association of SNPs with T2DM was performed using Pearson’s chi-square test. Haplotype frequency distribution, SNPs-SNPs interaction and environmental factors were analyzed by chi-square test and logistic regression.ResultsThe genotype distribution of SNPs rs2280148 of the SOCS3 gene was statistically significant. The allele frequency distribution of SNPs (rs4969168/rs2280148) was statistically different. After covariate correction, the SOCS3 gene locus (rs4969168) showed an association with T2DM in additive model, while the rs2280148 locus showed an association with T2DM in all three models. The locus (rs10974914/rs10815157) allele and genotype frequency distribution of JAK2 were statistically significant. After covariate correction, two SNPs in the gene showed association with T2DM in both additive and recessive models. The distribution of genotype frequencies of SNPs rs1053005 locus in gene STAT3 was statistically significant between the two groups. In recessive genetic models, rs1053005 locus polymorphisms was associated with T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene as well as haplotype J2 (A G)/J 3 (G C) of the JAK2 gene were closely associated with T2DM. There was an interaction between SNPs rs4969168 and SNPs rs2280148 in the SOCS3 gene. There was an interaction between the SOCS3, JAK2 and STAT3 genes and hypertension/triglycerides.ConclusionThe SOCS3 and JAK2 genes may be associated with T2DM in the Chinese population, in which SNPs carrying the A allele (rs4969168)/G allele (rs2280148)/C allele (rs10815157) have a reduced risk of T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene and haplotype J2 (A G)/J 3 (G C) of the JAK2 gene may be influencing factor for T2DM. The interaction between SNPs rs4969168 and SNPs rs2280148 increases the risk of T2DM. Hypertension and triglycerides may interact with SNPs of T2DM susceptibility genes.

Ethnicity Differences in the Association of UCP1-3826A/G, UCP2-866G/A and Ala55Val, and UCP3-55C/T Polymorphisms with Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis.

Background The relationship between uncoupling protein (UCP) 1-3 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) has been extensively studied, while conclusions remain contradictory. Thus, we performed this meta-analysis to elucidate whether the UCP1-3826A/G, UCP2-866G/A, Ala55Val, and UCP3-55C/T polymorphisms are associated with T2DM. Methods Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Heterogeneity analysis, subgroup analysis, sensitivity analysis, and publication bias were also performed. Results A total of 38 case-control studies were included in this meta-analysis. The overall results revealed significant association between T2DM and the UCP2 Ala55Val polymorphism (recessive model: OR = 1.25, 95% CI 1.12-1.40, P < 0.01; homozygous model: OR = 1.33, 95% CI 1.03-1.72, P = 0.029, respectively). In subgroup analysis stratified by ethnicity, T2DM risk was increased with the UCP2 Ala55Val polymorphism (allele model: OR = 1.17, 95% CI 1.02-1.34, P = 0.023; recessive model: OR = 1.28, 95% CI 1.13-1.45, P < 0.01; homozygous model: OR = 1.39, 95% CI 1.05-1.86, P = 0.023, respectively), while decreased with the UCP2-866G/A polymorphism in Asians (dominant model: OR = 0.86, 95% CI 0.74-1.00, P = 0.045). Conclusions Our results demonstrate that the UCP2-866G/A polymorphism is protective against T2DM, while the UCP2 Ala55Val polymorphism is susceptible to T2DM in Asians.

Association between Dietary Inflammatory Index and Type 2 diabetes mellitus in Xinjiang Uyghur autonomous region, China.

BackgroundDiet and inflammation have both been studied in relation to type 2 diabetes mellitus (T2DM). The aim of this cross-sectional study was to examine the association between the Dietary Inflammatory Index (DII®) and T2DM.MethodsSubjects were adults enrolled in the baseline study of the Xinjiang multi-ethnic natural population cohort and health follow-up study from January to May 2019. The study involved 5,105 subjects (58.7% men) between 35 and 74 years of age. The DII score was calculated from a data obtained via a food frequency questionnaire consisting of 127 food items.ResultsLogistic regression analyses were used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of DII in relation to T2DM. After adjusting for potential confounders, compared to subjects in the 1st DII quintile, subjects in the 5th quintile (i.e., with the most pro-inflammatory diet) had higher odds of T2DM (OR = 3.27, 95%CI:2.38,4.50; p < 0.001).ConclusionsOur results suggest that a pro-inflammatory diet is associated with a higher risk of T2DM in this population of Chinese adults.

Association of ACE I/D and PAI-1 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus.

A number of studies were carried out to assess the association of angiotensin I converting enzyme (ACE) I/D and plasminogen activator inhibitor-1 (PAI-1-1) 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus (T2DM). However, there are a few studies in Iranian patients with T2DM. Here, we tested for an association of ACE I/D and PAI-1 4G/5G polymorphisms with T2DM risk. One hundred-eighteen patients with T2DM and 125 healthy subjects were participates in this study. The ACE I/D (rs4340) and PAI-1 4G/5G (rs1799889) polymorphisms was genotyped by conventional and PCR-RFLP assays, receptively. The associations was evaluated by calculating the odds ratio (OR) and 95% confidence interval (95% CI). The genotype distribution of ACE I/D and PAI-1 4G/5G polymorphisms were not deviated from the Hardy-Weinberg equilibrium in healthy controls. The ACE II, ID, and DD genotype frequencies were 18.6%, 48.3%, and 33.1% in the T2DM patients versus 24.0%, 45.6% and 30.4% in healthy subjects, respectively. The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were 16.9%, 51.7%, and 31.4% in cases versus 24.8%, 57.6% and 17.6% in controls, respectively. There is a significant distribution in genotype/allele of PAI-1 4G/4G between cases with T2DM and healthy control, but not for ACE I/D. Moreover, the 5G/5G genotype is significantly (OR = 2.139,CI 95% 1.171-3.907, p = 0.013) increasedtheriskofT2DMby two folds in the cases than healthy controls. Our findings suggest that PAI-1 4G/5G may be likelihood risk factor for the development of T2DM in the Iranian patients. The higher frequency of PAI-1 5G/5G genotype in patients with T2DM revealed that individuals with the 5G allele may be at higher risk of T2DM development than those with 4G. However, there was no significant association between ACE I/D polymorphism and T2DM in our population. Future rigorous, well-designed studies with larger sample should replicate this study to confirm our findings in Iranian T2DM patients.

Meta-analysis: Interleukin 6 gene -174G/C polymorphism associated with type 2 diabetes mellitus and interleukin 6 changes.

The gene coding interleukin 6 (IL‐6) is a promising candidate in predisposition to type 2 diabetes mellitus (T2DM). This study aimed to meta‐analytically examine the association of IL‐6 gene −174G/C polymorphism with T2DM and circulating IL‐6 changes across −174G/C genotypes. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Twenty‐five articles were meta‐analysed, with 20 articles for T2DM risk and 9 articles for circulating IL‐6 changes. Overall, there was no detectable significance for the association between −174G/C polymorphism and T2DM, and this association was relatively obvious under dominant model (OR: 0.82, 95% CI: 0.56‐1.21). Improved heterogeneity was seen in some subgroups, with statistical significance found in studies involving subjects of mixed races (OR: 0.63, 95% CI: 0.46‐0.86). Begg's and filled funnel plots, along with Egger's tests revealed week evidence of publication bias. In genotype‐phenotype analyses, carriers of −174CC and −174CG genotypes separately had 0.10 and 0.03 lower concentrations (pg/mL) of circulating IL‐6 than −174GG carriers. Albeit no detectable significance for the association of −174G/C with T2DM, our findings provided suggestive evidence on a dose‐dependent relation between −174G/C mutant alleles and circulating IL‐6 concentrations, indicating possible implication of this polymorphism in the pathogenesis of T2DM.

Association of fourteen years diet quality trajectories and type 2 diabetes mellitus with related biomarkers.

Diet quality fluctuates throughout one’s adulthood, yet it remains unclear how long-term diet quality changes are related to type 2 diabetes mellitus (T2DM) and its biomarkers. We aimed to examine the association of long-term diet quality with T2DM and its biomarkers. Diet quality was assessed by the revised DBI-07, in which diet quality distance levels (DQD) represented the overall diet quality. Participants were clustered into classes sharing similar DQD levels using latent class mixed model. We used Cox regression and random effect linear regression to assess DQD trajectories’ association with T2DM and its biomarkers. Three DQD trajectories were derived: moderate to gradual decrease, high to moderate, high stable DQD level representing 2.14%, 6.18% and, 91.68% of the population. Compared to class 1, class 2 and 3 were associated with an increased risk of T2DM [HR=4.40; 95%CI: 2.02-9.59]; [HR=3.68; 95% CI: 2.11-6.43]. When class 3 was used as a reference, class 1 was also associated with an increased risk of TDM [HR=2.71; 95%CI: 1.55-4.73]. Our findings suggest that a long-term unhealthy diet is associated with an increased risk of T2DM. Gradually reducing DQD level may not make a difference, which establishes the importance of promoting healthy eating habits at early adulthood.

SLC30A8 gene polymorphism rs13266634 associated with increased risk for developing type 2 diabetes mellitus in Jordanian population.

Several genome-wide association studies (GWAS) have identified the single nucleotide polymorphism (SNP) rs13266634 in the Solute carrier family 30 member 8 (SLC30A8) gene as a risk factor to type 2 diabetes mellitus (T2DM). Nevertheless, other studies reported controversial findings of no significant association between the rs13266634 with T2DM. In this study, we aimed to investigate the association of this SNP with T2DM among Jordanian population in addition to define its corresponding allelic and genotypic frequencies. This case-control study enrolled 358 T2DM patients and 326 healthy controls who fulfilled the inclusion criteria. Blood samples were collected from all participants and were used for the rs13266634 SNP genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We demonstrated a significant association between the C/T rs13266634 SNP and T2DM among Jordanian population. A significant difference was found between the cases and controls regarding the allelic (P=0.003) distribution. Compared to people having T allele, those with C allele had higher risk of T2DM (OR=1.47 ; 95% CI: 1.14 - 1.89; P=0.003). Having a CC genotype versus TT genotype was significantly associated with increased risk to T2DM (OR=2.44; 95% CI: 1.16 - 5.12; P=0.019) after adjusting for age, gender, and BMI. Under the recessive model, subjects with CC genotype were more likely to have T2DM compared to those with CT or TT genotypes, (OR=1.64; 95% CI: 1.18 - 2.26; P =0.003) after adjusting for age, gender and BMI. The rs13266634 SNP is significantly associated with T2DM susceptibility among Jordanian Population.

Analysis of Uncoupling Protein 1 and β3-adrenergic Receptor Single Nucleotide Polymorphisms in Saudi Population with Type 2 Diabetes Mellitus

BACKGROUND: Uncoupling proteins (UCP) and β3-adrenergic receptor (ADRB3) gene polymorphism have been implicated in the susceptibility to type 2 diabetes mellitus (T2DM) but the results are inconsistent and inconclusive.&#x0D; AIM: The aim was to investigate the relationship between -3826A/G (rs1800592) of UCP 1 and ADRB3 Trp64Arg (C/T) (rs4994) gene polymorphism and the incidence of T2DM among Saudis.&#x0D; METHODS: Genotyping of both UCP1 and ADRB3 genes was carried out in 110 healthy controls and 108 unrelated Saudis with T2DM using polymerase chain reaction-based restriction fragment length polymorphism.&#x0D; RESULTS: The genotype and allele frequencies of the UCP1 gene did not differ significantly between diabetic subjects and controls (p &gt; 0.05). However, the CT genotype and the T allele of ADRB3 were higher in diabetic subjects compared with the controls while the CC genotype and C allele were higher in the controls relative to the diabetic subjects (Odds ratios [OR]: 7.85, 95% confidence interval [CI]: 4.23–14.59, p &lt; 0.001 and OR: 7.434 95% CI: 4.026–13.39, p &lt; 0.001, respectively).&#x0D; CONCLUSION: The UCP1 -3826A/G polymorphism may not be associated with the susceptibility to T2DM among Saudis while T allele of ADRB3 may be related to the risk of T2DM, whereas the CC genotype and C allele may confer protection to T2DM.