Risk Of To Type 2 Diabetes Mellitus Research Articles

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.
 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.
 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.
 RESULTS: The genotype and allele frequencies of the UCP1 gene did not differ significantly between diabetic subjects and controls (p > 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 < 0.001 and OR: 7.434 95% CI: 4.026–13.39, p < 0.001, respectively).
 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.

Preliminary evidence of insulin resistance in young adults with impaired sleep

Objective Impaired sleep is associated with insulin resistance (IR), a precursor to type 2 diabetes mellitus (T2DM), but is poorly understood in young adults. This cross-sectional study examined sleep characteristics, risk factors for T2DM, and IR in college students. Participants: Thirty-two college students (18–25 years) with either short sleep or poor quality sleep were assessed. Methods: Participants completed self-report measures of sleep and T2DM risk factors. One week of objective sleep was measured with wrist actigraphy. IR was calculated from fasting serum glucose and insulin concentrations. Results: The sample slept on average 6.6 hours/night, and over half had IR. Of those with IR, 44.4% had normal body mass index (BMI), 72% had normal fasting glucose concentrations, and all but one had T2DM risk test score indicating they were not at risk. Conclusions: IR was found in over half of participants; however, many typical T2DM risk factors were not present in those with IR.

495-P: Risk Factors for Incident T2DM in Patients with Prediabetes by CKD Status

Longitudinal data are critical to inform prediction of transition to type 2 diabetes mellitus (T2DM) from prediabetes. This study aimed to ascertain T2DM incidence and risk factors, including chronic kidney disease (CKD), in patients with prediabetes. The CURE-CKD registry of electronic health record data includes >2.6 million patients with and at-risk for CKD (T2DM, hypertension, prediabetes). Adults with prediabetes were identified by established criteria for % A1C, random and fasting glycemia, and administrative codes. T2DM was defined by corresponding established criteria. CKD was defined by estimated glomerular filtration rate <60 mL/min/1.73m2, urine albumin-to-creatinine ratio >30 mg/g based upon 2 or more measurements >90 days apart, and administrative codes. Cox proportional hazards regression was used to predict T2DM. From 2006 to 2017, there were 678,493 patients with prediabetes and baseline A1C 5.9±0.3% (mean±SD). Incident T2DM occurred in 185,770 (27%) at a mean of 3.6 years. At baseline, 134,240 (20%) had CKD. Adjusted for age, gender, race/ethnicity, and hypertension, hazard ratios for T2DM were greater in patients with CKD (1.44, 95%CI [1.42, 1.47]) and with increases in 1% A1C (4.59 95%CI [4.47, 4.72]). CKD was common in prediabetes and, along with higher A1C, demonstrated the greatest hazards for incident T2DM. Presence of CKD identifies patients with prediabetes who are high-risk for transition to T2DM. Disclosure K.A. Hennessey: None. R.Z. Alicic: None. K.B. Daratha: None. C. Jones: None. J.J. Neumiller: None. O. Duru: None. S. Nicholas: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Centers for Disease Control and Prevention, George Institute for Global Health, Goldfinch Bio, Inc., National Institutes of Health. S.M. McPherson: None. K.C. Norris: None. K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc.

Transcription factor 7-like 2 gene, rs12255372 (G/T) variant and susceptibility to type 2 diabetes mellitus in North Indians

BackgroundGenetic polymorphisms of the Transcription Factor 7-Like 2 (TCF7L2) gene have been shown to be strongly associated with susceptibility to type 2 diabetes mellitus (T2DM) and its related complications across several ethnicities. ObjectivesThe aim of the present study was to investigate the association of rs12255372 (G/T) polymorphism in TCF7L2 gene with the risk of T2DM in the Indian population. MethodsWe included a total of 712 human subjects (327 T2DM subjects and 385 healthy controls) for various anthropometric, biochemical and genetic parameters. Genotyping of TCF7L2 gene was carried out using the PCR-RFLP method. ResultsSignificantly higher values of body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), and body fat (%) were observed in T2DM subjects than controls (p ≤.001). Dyslipidemia represented by higher levels of triglycerides and reduced values of high-density lipoprotein (HDL) was more predominant in T2DM subjects compared to healthy controls. Both microvascular and macrovascular complications were predominant in T2DM patients than controls. The risk genotype (TT) frequency of TCF7L2 gene was significantly higher in T2DM subjects compared to controls (19.4% vs. 9.8%). The “T” allele was more predominant in T2DM subjects than healthy controls. Logistic regression analysis of the data indicates that the TT genotype of TCF7L2 gene is associated with appox. 2-fold increased risk of developing T2DM (OR = 1.91 95% CI (1.16–3.16); p = .014). Interestingly, no significant association among the genotypic distribution of metabolic traits in T2DM and healthy subjects. ConclusionThe present study established a significant association of TCF7L2 gene (rs12255372 (G/T) polymorphism) with a higher risk of T2DM in the North Indian population.

Progression to type 2 diabetes mellitus and associated risk factors after hyperglycemia first detected in pregnancy: A cross-sectional study in Cape Town, South Africa.

BackgroundGlobal data indicate that women with a history of hyperglycemia first detected in pregnancy (HFDP) are at up to 7 times risk of progressing to type 2 diabetes mellitus (T2DM) compared with their counterparts who have pregnancies that are not complicated by hyperglycemia. However, there are no data from the sub-Saharan African region, which has the highest projected rise in diabetes prevalence globally. The aim of this study was to determine the proportion of women who progress to T2DM and associated risk factors 5 to 6 years after HFDP in Cape Town, South Africa.Methods and findingsAll women with HFDP, at a major referral hospital in Cape Town, were followed up 5 to 6 years later using a cross-sectional study. Each participant had a 75 g oral glucose tolerance test; anthropometric measurements and a survey were administered. A total of 220 participants were followed up. At this time, their mean age was 37.2 years (SD 6.0). Forty-eight percent (95% CI 41.2–54.4) progressed to T2DM, 5.5% (95% CI 3.1–9.4) had impaired fasting glucose, and 10.5% (95% CI 7.0–15.3) had impaired glucose tolerance. Of the participants who progressed to T2DM, 47% were unaware of their diabetes status. When HFDP was categorized post hoc according to WHO 2013 guidelines, progression in the diabetes in pregnancy (DIP) group was 81% (95% CI 70.2–89.0) and 31.3% (95% CI 24.4–39.3) in the gestational diabetes mellitus (GDM) category. Factors associated with risk of progression to T2DM were; at follow-up: waist circumference (odds ratios [OR] 1.1, 95% CI 1.0–1.1, p = 0.007), hip circumference (OR 0.9, 95% CI 0.8–1.0, p = 0.001), and BMI (OR 1.1, 95% CI 1.0–1.3, p = 0.001), and at baseline: insulin (OR 25.8, 95% CI 3.9–171.4, p = 0.001) and oral hypoglycaemic treatment during HFDP (OR 4.1, 95% CI 1.3–12.9, p = 0.018), fasting (OR 2.7, 95% CI 1.5–4.8, p = 0.001), and oral glucose tolerance test 2-hour glucose concentration at HFDP diagnosis (OR 4.3, 95% CI 2.4–7.7, p < 0.001). Our findings have limitations in that we did not include a control group of women without a history of HFDP.ConclusionsThe progression to T2DM in women with previous HFDP found in this study highlights the need for interventions to delay or prevent progression to T2DM after HFDP. In addition, interventions to prevent HFDP may also contribute to reducing the risk of T2DM.

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population.

Objective: To evaluate the potential association between the genetic variants in miRNA processing genes (RAN, XPO5, DICER1, and TARBP2) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes.Methods: We conducted a case-control study in genotyping of five polymorphic loci, including RAN rs14035, XPO5 rs11077, DICER1 rs13078, DICER1 rs3742330, and TARBP2 rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too.Results: We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in DICER1 rs13078 (OR: 0.64; 95%CI: 0.42–0.95; P: 0.026). The AA haplotype in DICER1 was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42–0.94; P-value: 0.023). T2DM patients with the TT+TC genotype at RAN rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04–3.45; P-value: 0.037). We also identified two three-factor interaction models. One is a three-factor [DICER1 rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25–28.26; P = 0.025). Another three-factor [RAN rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM (OR = 41.60, 95%CI = 11.75–147.35, P < 0.001).Conclusion: Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, DICER1 and RAN, and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population.

Systematic Meta-analysis Revealed an Association of PGC-1α rs8192678 Polymorphism in Type 2 Diabetes Mellitus.

Background Genome-wide association study (GWAS) provides an unprecedented opportunity to reveal substantial genetic contribution to type 2 diabetes mellitus (T2DM) and glycemic identification of allelic heterogeneity and population-specific genetic variants, yet it also faces difficulty due to the vast amount of potential confounding factors and limited availability of clinical data. To identify responsible susceptibility loci and genomic polymorphism for T2DM and glycemic traits, we have systematically investigated a genome-wide association study related to T2DM. Although GWAS has captured many common genetic variations, which are related to T2DM, each risk allele (RA) of single-nucleotide polymorphisms (SNPs) at these loci is not conclusive. Therefore, it is common to present a combination of several SNPs to infer T2DM risk, yet it is still insufficient to be deterministic. To streamline the identification of a deterministic genetic variation in T2DM, we developed this meta-analysis as a showcase to comprehensively identify the association between cumulative RAs and T2DM risk by combining different studies in reported literature and databases. After all, we identified that PGC-1α rs8192678 polymorphism can be considered as a potentially deterministic biomarker in T2DM risk. Previous studies have potentially linked PGC-1α rs8192678 polymorphism to type 2 diabetes mellitus (T2DM) risk, but the results remain inconsistent in different populations and are not conclusive. We developed a new meta-analysis approach to systematically identify the association between PGC-1α rs8192678 polymorphism and T2DM, and we have comprehensively assessed different ethnic groups to validate our findings. Methods We performed comprehensive information retrieval and knowledge discovery meta-analysis by searching extensively published literature and different electronic databases to acquire eligible studies for the above association study. We developed a method to use pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) in five genetic models (allelic, dominant, recessive, homozygous, and heterozygous genetic models) to identify the relationship among ethnicity subgroup analyses comprehensively. Results We identified 20 eligible studies consisting of 16,182 subjects (8,038 cases and 8,144 controls) in our meta-analysis. PGC-1α rs8192678 polymorphisms of all subjects showed a significant association with T2DM susceptibility under all genetic models: allelic (OR: 1.24, 95% CI: 1.13-1.35), dominant (OR: 1.27, 95% CI: 1.14-1.42), recessive (OR: 1.24, 95% CI: 1.14-1.36), homozygous (OR: 1.40, 95% CI: 1.20-1.64), and heterozygous (OR: 1.20, 95% CI: 1.06-1.35). In the subgroup analysis, we identified a significant association between PGC-1α rs8192678 polymorphism and T2DM in the Caucasian and Indian populations under all genetic models we investigated. This is the most comprehensive study of the subject to date. Conclusion Our development of meta-analysis revealed that the minor allele (A) carriers, especially AA genotype carriers, can lead to risk of T2DM in the Caucasian and Indian populations. This is the first report that such risk has been confirmed. Our finding shed new light into the genetic alteration in T2DM.

Association of EGF A61G polymorphism and EGF expression with type 2 diabetes mellitus in Indian population

BackgroundEpidermal Growth Factor (EGF) plays critical role in regeneration of pancreatic β-cells and insulin secretion. The deficiency in EGF expression affects pancreatic β-cell's proliferation, maintenance and its function like insulin secretion which may result in individual susceptibility to Type 2 Diabetes Mellitus (T2DM). EGF A61G is a functional SNP that modulate EGF levels and eventually affects activity of β-cells. ObjectiveThe present study explores EGF A61G polymorphism (rs4444903) and correlates it with the risk of developing T2DM and mRNA expression. MethodsThe study included 90 subjects, T2DM patients (n = 30) and healthy controls (n = 60). Blood sample was collected from subjects to study EGF A61G polymorphism by PCR-RFLP and EGF mRNA expression level by Real-time PCR. ResultsThe EGF gene A61G polymorphism was found to be in significant association with T2DM. A/G genotype (OR = 4.07, 95%CI = 1.303 to 12.71, p = 0.0206) and ‘A’ allele (OR = 1.91, 95%CI = 1.017 to 3.568, p = 0.043) were significantly associated with risk of T2DM. The prevalence of allele ‘A’ was found to be higher in diabetic males and females (52.5% and 55% respectively). As compared to healthy subjects EGF mRNA expression levels showed significant down-regulation in T2DM patients (p = 0.005). The relative EGF mRNA expression in A/A and A/G genotype was significantly lower than G/G genotype. ConclusionThe present study suggests that EGF gene A61G polymorphism may be a genetic risk factor for susceptibility of T2DM in Indian population. However, this marker deserves further investigation using more sample size.

Ethnicity-Specific Association Between Ghrelin Leu72Met Polymorphism and Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis.

Background: The Leu72Met polymorphism of ghrelin gene has been associated with genetic predisposition to type 2 diabetes mellitus (T2DM), while conclusions remain conflicting. Hence, we performed this updated meta-analysis to clarify the association between Leu72Met polymorphism and T2DM susceptibility.Methods: Six electronic databases were consulted for articles published before 1 January, 2018. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated under five genetic models to assess this association. We used I2-test and Q statistics to measure heterogeneity across the included studies. Subgroup analyses and publication bias were also performed.Results: Thirteen case-control studies involving 4720 T2DM patients and 4206 controls were included in this meta-analysis. The overall results using fixed-effects models showed that Leu72Met polymorphism was significantly associated with an increased risk of T2DM under homozygous model (OR = 1.307, 95%CI 1.001–1.705, p = 0.049). Further subgroup analyses stratified by ethnicity revealed that the risk for T2DM was only increased in Asians (homozygous model: OR = 1.335, 95%CI 1.014–1.758, p = 0.040), while decreased in Caucasians (dominant model: OR = 0.788, 95%CI 0.635–0.978, p = 0.030; heterozygous model: OR = 0.779, 95%CI 0.626–0.969, p = 0.025; allelic model: OR = 0.811, 95%CI 0.661–0.995, p = 0.045). Funnel plots were basically symmetrical, and all p-values of Egger's test under five genetic models were >0.050, which indicated no evidence of publication bias.Conclusions: Our results demonstrate that the Leu72Met polymorphism of ghrelin gene may be protective against T2DM in Caucasians, while predisposing to T2DM in Asians.

Low serum creatinine predicts risk for type 2 diabetes.

As an insulin target tissue, skeletal muscle is inversely related to type 2 diabetes mellitus (T2DM). Serum creatinine originates mainly from creatine in muscle and is considered as a reliable surrogate marker for muscle mass in apparently healthy subjects. It is therefore hypothesized that low serum creatinine could effectively predict increased risk of T2DM. Yet information is scarce regarding the longitudinal relationship between serum creatinine and T2DM. This study aims to investigate this relation in a large general population of both men and women. A prospective cohort study (n=57587; follow-up range: 1-9years, mean: 3.57years, 95% confidence interval: 3.55-3.58years) was conducted in a general population sample from Tianjin, China. Multivariable Cox proportional hazards regression models were used to assess the relationship between baseline serum creatinine and the risk of developing T2DM (as defined by the American Diabetes Association criteria). During the follow-up period, 2017 subjects developed T2DM. The multivariate-adjusted hazard ratios (95% confidence interval) for T2DM incidence across quintiles of serum creatinine were 1.00 (reference), 0.86 (0.75, 0.99), 0.82 (0.72, 0.94), 0.85 (0.74, 0.97), and 0.77 (0.67, 0.89; P for trend <.01). Similar results were observed in both sexes (interaction P=.56). These findings indicate that serum creatinine concentration is inversely related to incident T2DM in both men and women. Measuring serum creatinine may assist in the early detection of individuals at high risk of developing T2DM.

European versus Asian differences for the associations between paraoxonase-1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus.

Many studies have examined the associations between paraoxonase‐1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta‐analysis to clarify the association of the two PON1 variants with T2DM risk. We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios (ORs) for the association and their corresponding 95% confidence intervals (CIs) were calculated by a random‐ or fixed‐effect model. A total of 50 eligible studies, including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1, P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45–0.98) under a heterozygous genetic model. With regard to the PON1 L55M polymorphism, significant protective effects of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61–0.97) and dominant (OR = 0.80, 95% CI = 0.65–0.99) genetic models were found in the European population, while no significant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta‐analysis, our results firmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic backgrounds.

Study and evaluation the impact of vitamin D receptor variants on the risk of type 2 diabetes mellitus in Han Chinese.

Vitamin D and the vitamin D receptor (VDR) are associated with susceptibility to type 2 diabetes mellitus (T2DM). The purpose of the present study was to screen more single nucleotide polymorphisms (SNPs) of VDR and assess their effects on the risk of T2DM in Han Chinese. Four SNPs were genotyped in 1191 individuals (397 cases, 794 controls). Allele frequencies and genotype distributions were analyzed. Effects were investigated by evaluating genotype distribution with regard to phenotypes, insulin resistance, and β-cell function. Haplotype analysis and gene risk score (GRS) were used to evaluate the combined and additive roles of VDR SNPs on T2DM pathogenesis. There was a significant association between rs739837 and T2DM in two models and allele frequency distribution. The novel locus rs2239179 differed significantly between cases and controls, especially in males and those aged >55 years, in three models and allele frequency distribution. The TT genotype of rs739837 was associated with higher triglyceride than GG and TG genotypes, and higher total cholesterol levels than the GG genotype. Compared with the GTGA haplotype, the GCGG haplotype reduced the risk of T2DM. Trend Chi-squared tests showed that there was significant association between the weighted GRS and the risk of T2DM (Ptrend = 0.034). This study provides novel evidence that rs739837 is associated with lipid metabolism in T2DM patients. The rs739837 and rs2239179 SNPs were associated with the risk of T2DM in Han Chinese. The VDR SNPs had combined and additive effects on the risk of T2DM.

Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population.

Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the genetic variants might be used as molecular markers for evaluating the risk of T2DM and diabetic nephropathy. © 2016 IUBMB Life, 68(7):516-525, 2016.

Low Carbohydrate-Diet Scores and Long-term Risk of Type 2 Diabetes Among Women With a History of Gestational Diabetes Mellitus: A Prospective Cohort Study.

Low-carbohydrate diets (LCDs) may improve short-term glycemic control in patients with gestational diabetes mellitus (GDM), but the long-term effect on progression from GDM to type 2 diabetes mellitus (T2DM) is unknown. We aimed to examine the long-term risk of T2DM in association with a low-carbohydrate dietary pattern among women with a history of GDM. Overall, 4,502 women with a history of GDM from the Nurses' Health Study II (NHSII) cohort, as part of the Diabetes & Women's Health (DWH) study, were followed up from 1991 to 2011. Overall, animal, or vegetable LCD scores, which represent adherence to different low-carbohydrate dietary patterns, were calculated using diet intake information assessed every 4 years since 1991 by validated food-frequency questionnaires. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. We documented 722 incident cases of T2DM during 68,897 person-years of observation. The multivariable-adjusted HRs (95% CIs) of T2DM, comparing the highest with lowest quintiles, were 1.36 (1.04-1.78) for overall LCD score (P = 0.003 for trend), 1.40 (1.06-1.84) for animal LCD score (P = 0.004 for trend), and 1.19 (0.91-1.55) for vegetable LCD score (P = 0.50 for trend). Among women with a history of GDM, a low-carbohydrate dietary pattern, particularly with high protein and fat intake mainly from animal-source foods, is associated with higher T2DM risk, whereas a low-carbohydrate dietary pattern with high protein and fat intake from plant-source foods is not significantly associated with risk of T2DM.

Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms in type 2 diabetes mellitus: A meta-analysis of 15,059 subjects

AimsToll-like receptor 4 (TLR4) gene Asp299Gly and Thr399Ile polymorphisms have been reported to be associated with susceptibility to type 2 diabetes mellitus (T2DM) with inconsistent results. In an effort to clarify earlier inconclusive results, a meta-analysis evaluating the precise associations between TLR4 gene Asp299Gly and Thr399Ile polymorphisms and T2DM risk was performed. MethodsWe searched the PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar until July 17, 2014. Additionally, hand searching of the references of identified articles were performed. Original observational studies dealing with the associations between TLR4 gene Asp299Gly and Thr399Ile polymorphisms and T2DM risk were selected. Heterogeneity and publication bias were determined and the meta-analysis was performed by Review Manager 5.1.4 and Stata 11.0. ResultsSeventeen articles involving 25 studies were included in the final meta-analysis, covering a total of 5963 T2DM cases and 9096 controls. For TLR4 gene Asp299Gly polymorphism, 17 studies were combined showing no evidence for association between TLR4 gene Asp299Gly polymorphism and T2DM risk. For TLR4 gene Thr399Ile polymorphism, eight studies were combined. There was also lack of evidence for significant association between TLR4 gene Thr399Ile polymorphism and T2DM risk. In addition, the similar results were obtained in the sensitivity analyses. ConclusionsThe present meta-analysis indicates that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with increased T2DM risk.

Type 2 Diabetes Mellitus and the Association of Candidate Genes in Asian Indian Population from Hyderabad, India.

Genetic and environmental factors play an important role in susceptibility to type 2 diabetes mellitus (T2DM). Several genes have been implicated in the development of T2DM. Genetic variants of candidate genes are, therefore, prime targets for molecular analysis. In this study, we have selected 3 candidate genes, namely, TCF7L2, SLC30A8, and IGF2, for assessing their association with T2DM in an Indian population. Five hundred individuals were enrolled in this case-control study- 250 T2DM patients and 250 healthy control individuals. Clinical characteristics were obtained for all subjects, and genotype analysis was performed by PCR-RFLP analysis. Allele and genotyping frequencies, odds ratios, and 95% confidence intervals were calculated for 3 single nucleotide polymorphisms (SNPs), 1 each from TCF7L2 (rs7903146), SLC30A8 (rs13266634), and IGF2 (rs680) in T2DM patients. The rs7903146 and rs680 polymorphisms were found to be significantly associated with T2DM (p < 0.05), whereas the rs13266634 polymorphism was not (p > 0.05). The multifactor dimensionality reduction method identified the particular polymorphisms associated with an increased risk of disease. The present study indicated that the gene-gene interaction model successfully predicted T2DM risk based on TCF7L2 and SLC30A8 polymorphisms. These results provide strong evidence of independent association between T2DM and the 3 SNPs analysed herein.

Association of TLR4 gene polymorphisms with susceptibility to type 2 diabetes mellitus in the Chinese Han population.

Toll-like receptor 4 (TLR4) gene plays important roles in the susceptibility to type 2 diabetes mellitus (T2DM). This study aims to detect the potential association of TLR4 gene polymorphisms with the susceptibility to T2DM in the Chinese Han population. 685 T2DM patients and 690 healthy controls were enrolled in this case-control study. The genotypes of TLR4 gene polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods. We detected the g.13726T>C and g.15090G>A genetic polymorphisms. Our data supported that the g.13726T>C and g.15090G>A genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the homozygote comparison, recessive model, and allele contrast (all P-values<0.01). The allele-C and genotype-CC of g.13726T>C and allele-A and genotype-AA of g.15090G>A genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. These preliminary findings indicate that the g.13726T>C and g.15090G>A genetic polymorphisms of TLR4 gene are potentially related to the susceptibility to T2DM in the studied population, and might be used as molecular markers for evaluating the risk of T2DM.

The Impact of Cigarette Smoking on Metabolic Syndrome

Metabolic syndrome (MetS) is a constellation of interconnected cardiometabolic disorders, including obesity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is a precursor to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD); it increases the risk of T2DM by 3-4 times and the risk of CVD by 1.4-fold, and is more prevalent in obese individuals. As the obesity rates increase, the prevalence of MetS in the population is increased. In 2006, the global prevalence of MetS in adults was estimated to be 20%-25%, and in China, in 2007-2008, using the criteria of the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG), it reached 21.9% among the adult population aged ≥20 years old. Smoking is a significantand modifiablerisk factor for many of the common chronic diseases, such as cancer, lung disease, and CVD, and is a potential MetS risk factor. Many people are active or passive smokers; globally, 1.1 billion people are smokers, which is approximately one third of the adult population. In 2002, the Chinese National Survey described 350 million active smokers, and 540 million passive smokers, aged between 15 and 69 years of age. Consequently, the impact of smoking on MetSand other diseasesis of great interest. The association between active smoking and MetS risk, or the risk of one of its associated disorders, is not fully understood. Among more than 1 000 components, nicotine is the best-known of the major harmful components released from cigarette smoke. Nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central and peripheral nervous system. As ligand-gated ion channels, nicotine mediates a fast synaptic transmission of the neurotransmitter at the neuromuscular junction and ganglia through binding to nAChRs. This directly or indirectly augments the release of several important neurotransmitters and hormone, mainly including arginine vasopressin (AVP), corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), growth hormone (GH), dopamine (DA), serotonin, glutamate, and γ-aminobutyric acid in the central nervous system, acetylcholine (ACh) in the central and peripheral nervous system, epinephrine and norepinephrine by the adrenal medulla, cortisol by the adrenal cortex. Note that the hypothalamic-pituitary-adrenal axis (HPA) and the renin-angiotensin-aldosterone system (RAAS) have been implicated in those processes. So it is obvious that there are associations between smoking and some metabolic disorders. Here, we review the associations between smoking and MetS, and smoking and its associated disorders, and present the available evidence of the risk of MetS associated with smoking.