Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort.

BACKGROUND: To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. METHODS: Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. RESULTS: During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1-2, 3, 4-5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. CONCLUSIONS: High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

CircRNA hsa_circ_0071336 is associated with type 2 diabetes through targeting the miR-93-5p/GLUT4 axis.

Glucose transporter 4 (GLUT4) is a dominant regulator of whole-body glucose homeostasis. Accumulating evidence has shown that circular RNAs (circRNAs) play significant roles in the pathogenesis of disease. The aim of the present study was to identify the circRNA that can be used as a novel biomarker for type 2 diabetes (T2D) through regulating GLUT4. Based on previous microarray analysis comparing T2D cases and healthy controls, hsa_circ_0071336, which was predicted to be a regulator of GLUT4 by acting as a competitive endogenous RNAs (ceRNA) to sponge miR-93-5p, was selected for further validation. The clinical significance of circulating hsa_circ_0071336 was investigated in a large independent cohort. The results showed that circulating hsa_circ_0071336 was significantly downregulated in blood in T2D and had a high diagnostic accuracy for discriminating T2D and impaired fasting glucose (IFG) from healthy controls. Low expression of circ_0071336 was an independent predictor of T2D, IFG and insulin resistance. A luciferase reporter assay and western-blot analysis indicated that miR-93-5p was a direct target of hsa_circ_0071336, and miR-93-5p may negatively regulate the expression of GLUT4. The expression levels of hsa_circ_007136 were negatively related to miR-93-5p expression and positively correlated with the mRNA expression of GLUT4 in adipose tissues. In conclusion, hsa_circRNA_0071336 can be considered as a potential novel and stable biomarker for T2D and its early detection. hsa_circ_0071336 regulates the GLUT4 expression by sponging miR-93-5p and maybe involved in the pathogenesis of T2D. These findings may unveil new targets for the prevention, diagnosis and treatment of T2D.

The effects of short-term exposure to air pollution on mortality in Baotou, China, during 2015-2019.

Air pollution was considered one of the main causes linked to increased morbidity and mortality around the world. This study aimed to estimate the effect of air pollutants on daily death in Baotou city of Inner Mongolia. Daily deaths data were provided by Baotou Centers for Disease Control and Prevention for the years 2015-2019 (Baotou CDC). The air pollutants, PM2.5, PM10, NO2, SO2, CO and maximum 8-h average concentrations of O3, came from the eight environmental monitoring stations in Baotou city. Time-series plots were used to exploit the trend of air pollutants at calendar time. Generalized additive model was used to estimate the effect of air pollutants on daily death. Restricted cubic spline was employed to investigate non-line relationships between air pollutants and daily death. After adjusting the meteorological factors, non-accidental daily deaths were related to PM2.5 (ER = 0.074%) and PM10 (ER = 0.023%), respectively. In stratified analysis, population aged over 65 years and females were more sensitive to air pollutants exposure and warm season might make people more susceptible to air pollutants compared with cold season. PM2.5 and PM10 increase the risk of non-accidental and cardiovascular daily death, but not respiratory daily death.

Gender-specific predictive ability for the risk of hypertension incidence related to baseline level or trajectories of adiposity indices: a cohort study of functional community.

BACKGROUND: Early prevention of hypertension is important for global cardiovascular disease morbidity and mortality. This study aims to explore better predictors for hypertension incidence related to baseline level or trajectories of adiposity indices, as well as the gender-specific effect. METHODS: 6085 subjects from a functional community cohort in urban Beijing participated in our study. Restricted cubic splines were used to estimate nonlinear associations of body mass index (BMI) and waist-to-height ratio (WHtR) as continuous variable with risk of hypertension. Stepwise logistic regression model was performed to estimate the relative risks (RRs) of adiposity indices and metabolic status, adjusted for covariates. Nomogram models and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of BMI trajectory groups and WHtR trajectory groups on hypertension incidence. Further, all analysis were performed by gender. RESULTS: The risk of hypertension incidence was related to BMI trajectory groups (persistent overweight: RR = 1.88, 95% CI: 1.48-2.37; persistent obesity: RR = 2.79, 95% CI: 2.18-3.56; persistent the highest: RR = 4.30, 95% CI: 3.20-5.78) and WHtR trajectory groups (persistent medium: RR = 2.69, 95% CI: 2.07-3.50; persistent high: RR = 3.85, 95% CI: 2.92-5.09; increasing to higher: RR = 7.00, 95% CI: 4.96-9.89). In total population, BMI trajectories and WHtR trajectories showed similar ability to predict the risk of hypertension incidence with AUC 0.723 and 0.726, respectively. After stratified by gender, both BMI trajectories and WHtR trajectories showed higher power in female than male (BMI trajectories: 0.762 vs. 0.661; WHtR trajectories: 0.768 vs. 0.661). CONCLUSIONS: BMI and WHtR trajectories have higher predictive power for hypertension incidence compared to baseline data. Females are more vulnerable to obesity than males.

Association between insulin resistance and incidence of carotid atherosclerotic plaque: A cohort study.

BACKGROUND AND AIMS: There is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study. METHODS AND RESULTS: The study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose-response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose-response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14-2.04), 1.86 (1.40-2.46), and 2.55 (1.94-3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08-1.90), 1.59 (1.20-2.12), and 1.69 (1.26-2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025). CONCLUSION: IR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.

Association of household solid fuel use and long-term exposure to PM2.5 with arthritis in middle-aged and older population in China: A cohort study.

Air pollutants are common modifiable risk factors for arthritis. To explore the longitudinal effects of air pollution on arthritis based on a cohort study in middle-aged and elder people of China. Data was obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 7449 participants aged 45 years and older were involved in our study. The generalized linear mixed models were conducted to examine the separate and joint effects of household air pollution and outdoor air pollution on arthritis, respectively. We found a strong significant association between air pollution and arthritis incidence. Individuals cooking primarily with solid fuel were more likely in higher risk of arthritis compared with cleaner fuel (OR= 1.15; 95% CI: 1.08-1.23). The group-based trajectory model identified four trajectory groups, compared with group "High-Decreasing rapidly", adjusted ORs of incident arthritis for group "Middle-Decreasing moderately", "Low-Decreasing slowly" and "Low-Stably" were 1.36 (95% CI, 1.03-1.79), 1.36 (95% CI, 1.01-1.83) and 1.81 (95% CI, 1.30-2.52), respectively. These associations were generally higher in participants younger than 65 years. In addition, solid fuel use and PM2.5 exposure had additive and multiplicative effects on arthritis. The results suggested that solid fuel use and long-term PM2.5 exposure were associated with a higher incidence of arthritis. Therefore, it is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to reduce PM2.5 concentration.

Pri-miR-144 rs9279 is associated with type 2 diabetes and regulation of stress response.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) may alter miRNA expression, binding affinity, and/or messenger RNA expression levels of the target genes, thus leading to disease susceptibility. This study explored the association between SNPs in neuroendocrine stress response-related miRNAs and type 2 diabetes (T2D). In the screening stage, the association between six candidate SNPs of miRNAs and T2D was analyzed in a case-control study including 504 T2D cases and 494 healthy controls. Homozygous GG genotype of pri-miR-144 rs9279 showed significant association with increased risk of T2D compared with homozygous TT genotype (adjusted odds ratio [OR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; p = .023) and the combined TT/TG genotype (adjusted OR = 1.59, 95% CI: 1.08-2.36; p = .020). In the validation stage, the association was further validated in a second independent set of subjects. The GG genotype showed consistent directions and effect sizes that were identified in previous additive and recessive models. The expression levels of miRNAs were further compared between different genotypes in the 179 newly diagnosed cases and 183 frequency-matched healthy controls. As a result, the GG genotype carriers had significantly upregulated expression of plasma miR-144 and cortisol, as compared to individuals with TT and TG genotypes, respectively, in total subjects and subgroups (p < .05). Eventually, NR3C1 was proved to be a stress-related target gene of miR-144, indicating that pri-miR-144 rs9279 may contribute to the development of T2D by altering regulation of stress response.

A novel strategy of identifying circRNA biomarkers in cardiovascular disease by meta-analysis.

Circular RNAs (circRNAs) are stable and abundantly expressed in vivo but are abnormally expressed in several diseases. This study aimed to identify circRNAs acting as potential biomarkers for cardiovascular disease (CVD). Research were retrieved from the articles published by September 2018 in eight databases to compare circRNA expression profiles between CVD and non-CVD in human and animal models. Meta-analysis under a random effects model was conducted. Subgroup analysis of tissue, species, and disease-specific circRNAs was examined. Sensitivity analysis was performed to explain the uncertainty among all studies. Diagnostic accuracy of circRNAs in CVD was analyzed to testify the discriminative ability. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted. Among 6,284 differentially expressed circRNAs from 32 original studies, only 322 circRNAs were reported in three or more studies. The meta-analysis identified 63 significantly dysregulated circRNAs, 44 upregulated and 19 downregulated. Among the tissue-specific or disease-specific circRNAs identified in the subgroup analysis, two circRNAs (circCDKN2BAS and circMACF1) showed the potential to be circulating biomarkers for CVD. Sensitivity analysis demonstrated 69% of circRNAs were in conformity with the overall analysis. The pooled diagnostic odds ratio was 2.94 (95% confidence interval [CI], 2.35-3.58), and the overall area under the curve value was 0.86 (95% CI, 0.83-0.89). GO and KEGG enrichment analyses indicated that the target genes of circRNAs participate in cardiogenesis-related processes and pathways. This study demonstrates circRNAs have a high diagnostic value as potential biomarkers for CVD, and two candidate circRNAs, circCDKN2BAS and circMACF1, are potential circulating biomarkers for CVD diagnosis and treatment.

Expression of miR-18a and miR-34c in circulating monocytes associated with vulnerability to type 2 diabetes mellitus and insulin resistance.

Chronic stress may facilitate the development of metabolic disorders including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). MiR-18a and miR-34c modulate central cell responsiveness to stress by targeting glucocorticoid receptor (GR) and corticotropin-releasing factor receptor type 1 (CRFR1) mRNA, which are important regulators of the hypothalamus-pituitary-adrenal (HPA) axis. This study explored the relationship between T2DM/IR and expression of miR-18a and miR-34c in peripheral blood mononuclear cells (PBMCs) in an occupational sample. Three groups of study subjects were involved, including T2DM patients, impaired fasting glucose (IFG) individuals and healthy controls. The degree of IR was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR). The expression of miR-18a and miR-34c in PBMCs was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Expression levels of miR-18a and miR-34c were significantly correlated with cortisol, corticotropin-releasing factor (CRF) and interleukin 6 (IL-6) (P < 0.05). The increased levels of miR-18a were associated with risk of T2DM (adjusted OR = 1.48, 95% CI: 1.25-1.75, P < 0.001) and IFG (adjusted OR = 1.33, 95% CI: 1.09-1.63, P = 0.005). By contrast, the decreased levels of miR-34c were associated with risk of T2DM (adjusted OR = 0.81, 95% CI: 0.75-0.88, P < 0.001) and IFG (adjusted OR = 0.87, 95% CI: 0.81-0.94, P < 0.001). After adjusting for potential confounders, miR-18a and miR-34c were independent positive and negative predictors of HOMA-IR, respectively (P < 0.001). The miRNA panel with the two miRNAs demonstrated high accuracy in the diagnosis of T2DM (AUC = 0.851, 95% CI: 0.786-0.800, P < 0.001). MiR-18a and miR-34c in PBMCs may be important marker of stress reaction and may play a role in vulnerability to T2DM as well as IR.

Investigation of the Relationship Between Chronic Stress and Insulin Resistance in a Chinese Population.

BACKGROUND: Chronic stress may facilitate the development of metabolic diseases. Insulin resistance is present long before the clinical manifestations of individual metabolic abnormalities. To explore whether chronic stress is an independent risk factor of insulin resistance, we investigated the relationship between the stress system, selected parameters of energy homeostasis, and insulin resistance in a Chinese population. METHODS: We recruited 766 workers employed at four companies in Beijing. The degree of insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). The highest quartile of HOMA-IR among all study subjects was further defined as insulin resistance in our study. The short standard version of the Copenhagen Psychosocial Questionnaire (COPSOQ) was used to assess job-related psychosocial stress. Pearson's correlation coefficients were calculated between cortisol level and HOMA-IR and components of metabolic syndrome, with stratification by gender. The relationship between cortisol and HOMA-IR independent of obesity was analyzed using a linear mixed model with company as a cluster unit. RESULTS: The values of the two scales of COPSOQ, including "demands at work" and "insecurity at work", were significantly associated with insulin resistance and cortisol concentration (P < 0.05). Cortisol was significantly positively correlated with glucose, HOMA-IR, and waist circumference in males and females (P < 0.05). After adjusting for potential confounders, cortisol was an independent positive predictor for HOMA-IR (P < 0.05). CONCLUSIONS: These findings showed that chronic stress was associated with insulin resistance and may contribute to the development of insulin resistance.

Association of suboptimal health status with psychosocial stress, plasma cortisol and mRNA expression of glucocorticoid receptor α/ß in lymphocyte.

Suboptimal health status (SHS) has become a new public health challenge in China. This study investigated whether high SHS is associated with psychosocial stress, changes in cortisol level and/or glucocorticoid receptor (GR) isoform expression. Three-hundred eighty-six workers employed in three companies in Beijing were recruited. The SHS score was derived from data collection in the SHS questionnaire (SHSQ-25). The short standard version of the Copenhagen Psychosocial Questionnaire (COPSOQ) was used to assess job-related psychosocial stress. The mean value of the five scales of COPSOQ and distribution of plasma cortisol and mRNA expression of GRα/GRß between the high level of SHS group and the low level of SHS group were compared using a general linear model procedure. Multiple linear regression analysis was used to analyze the effect of psychosocial stress on SHS. We identified three factors that were predictive of SHS, including "demands at work", "interpersonal relations and leadership" and "insecurity at work". Significantly higher levels of plasma cortisol and GRß/GRα mRNA ratio were observed among the high SHS group. High level of SHS is associated with decreased mRNA expression of GRα. This study confirmed the association between chronic psychosocial stress and SHS, indicating that improving the psychosocial work environment may reduce SHS and then prevent chronic diseases effectively.

Let-7 related genetic variation and risk of metabolic syndrome in a Chinese population.

MicroRNA (miRNA) related genetic variation may change miRNA binding affinity and mRNA expression levels of the target genes, thus leading to altered metabolic parameters. This study explored the influence of let-7 related single nucleotide polymorphisms (SNPs) on individual susceptibility to metabolic syndrome (MetS) in a Chinese population. Seven SNPs located at the pri-let-7 gene region, pre-let-7 gene region or 3'-UTR of the KRAS gene were selected. The SNPs were genotyped in 503 MetS patients and 529 normal controls using the high-throughput Sequenom genotyping platform. Unconditional logistic regression analysis was utilized to estimate the association between these SNPs and the risk of MetS. There are three SNPs significantly associated with MetS. The A allele of rs17276588 was associated with an increased risk effect for MetS (Adjusted OR=1.75, 95%CI 1.37-2.25, P<0.001). Rs10993081 AG genotype was significantly associated with an increased risk of MetS compared with AA genotypes (Adjusted OR=1.42, 95%CI 1.11-1.83, P=0.006). Rs10877887 TC genotype was significantly associated with an increased risk of MetS compared with TT genotypes (Adjusted OR=1.52, 95% CI 1.16-1.99, P=0.002). Additionally, interactions between rs7045890 and rs712, rs17276588 and rs10877887 were significantly associated with risk of MetS. In conclusion, our study found that let-7 related genetic variation is associated with MetS and may contribute to the susceptibility of MetS. Larger, prospective studies are warranted to validate our findings.

Association of household solid fuel use and long-term exposure to ambient air pollution with estimated 10-year high cardiovascular disease risk among postmenopausal women.

This study aimed to explore the separate and joint effects of long-term ambient air pollution and household air pollution exposure on 10-year high cardiovascular disease (CVD) risk among postmenopausal women. A total of 4679 postmenopausal women from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. Information of fuel type was collected by standard questionnaires and use of solid fuel was considered as a proxy for household air pollution. Data of ambient air pollutants (PM1, PM2.5, PM10, SO2, NO2, CO, O3) were obtained from the ChinaHighAirPollutants (CHAP) datasets. Logistic regression models were performed to assess the separate and joint effects of long-term exposure to ambient air pollution and use of solid fuel on 10-year high CVD risk. We found use of solid fuel and its duration and ambient air pollutants (PM1, PM2.5, PM10, SO2, NO2) were all positively associated with 10-year high CVD risk among postmenopausal women (P < 0.05). Compared to those used clean fuel and exposed to low ambient air pollution levels, odds ratios (ORs) and 95% confidence intervals (CIs) for participants using solid fuels and exposed to high ambient air pollution levels (PM1, PM2.5, PM10, SO2, NO2, CO, O3) were 1.66 (1.35, 2.05), 1.66 (1.35, 2.04), 1.49 (1.22, 1.83), 1.28 (1.05, 1.57), 1.67 (1.34, 2.07), 1.28 (1.04, 1.57), 1.46 (1.18, 1.80), respectively. Moreover, significant additive interactions of solid fuel use with PM1 and PM2.5 on 10-year high CVD risk were observed, with approximately 18% and 23% of 10-year high risk of CVD attributable to the interaction. Overall, indoor and outdoor air pollution had separate and joint effects on 10-year high CVD risk among postmenopausal women. Therefore, simultaneously improving indoor and outdoor air quality are of great importance and could have a joint impact on prevention of CVD and improved health among postmenopausal women.

The role of m6A modification in type 2 diabetes: A systematic review and integrative analysis.

This study focuses on the latest developments in the studies of m6A modification and provides an up-to-date summary of the association between m6A modification and type 2 diabetes (T2D). The possible mechanisms of m6A related to T2D were summarized by literature review. The differentially expressed genes (DEGs) of m6A methylase in T2D were analyzed from 12 datasets in Gene Expression Omnibus (GEO). The associations between m6A level and T2D were explored in four electronic databases, including PubMed, EmBase, Web of Science and CNKI. Standard mean difference (SMD) and 95 % confidence interval (95 %CI) was calculated to assess the total effect in integrative analysis. Differential expression genes detected in at least three of six tissues were ZC3H13, YTHDC1/2, and IGF2BP2. LRPPRC were differentially expressed in five tissues except in arterial tissue. A total of 6 studies were included for integrative analysis. The mean m6A levels were significantly lower in T2D than those in normal controls (SMD = -1.35, 95 %CI: -2.58 to -0.11). This systematic review and integrative analysis summarize the previous studies on the association between m6A modification and T2D and the possible role of m6A modification in the progression of T2D, such as abnormal blood glucose, abnormal pancreatic ß-cell function, insulin resistance, and abnormal lipid metabolism. The integrative analysis showed that decreased level of m6A was associated with T2D. These findings provide new targets for early detection and treatment for T2D.

Proteomics in Cardiovascular disease.

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD.

Association of phenotypic frailty and frailty index with type 2 diabetes and dyslipidemia in middle-aged and elderly Chinese: A longitudinal cohort study.

PURPOSE: Frailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI). MATERIALS AND METHODS: Multivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia. RESULTS: 10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05). CONCLUSION: Frailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator.

Identification of circular RNA hsa_circ_0034621 as a novel biomarker for carotid atherosclerosis and the potential function as a regulator of NLRP3 inflammasome.

BACKGROUND AND AIMS: NLRP3 inflammasome plays a key role in vascular inflammation and atherosclerosis. Circular RNAs (circRNAs) are involved in disease development by regulating gene expression, and have emerged as promising novel disease biomarkers. This study aimed to identify the NLRP3 inflammasome-associated circRNA biomarkers of carotid atherosclerosis. METHODS: Based on the differential expression profiles of circRNAs in patients with carotid artery plaque (CAP) and healthy controls, hsa_circ_0043621, hsa_circ_0051995, and hsa_circ_0123388 were screened and validated using real-time quantitative polymerase chain reaction (RT-qPCR). Potential circRNA-miRNA-mRNA interactions were explored using a luciferase assay. The biological roles of the validated circRNAs were investigated in human umbilical vein endothelial cells (HUVECs) using Western blotting, transwell, and CCK-8 assays. Clinical significance was assessed using receiver operating characteristic (ROC) curves and logistic regression analysis. RESULTS: The expression levels of all candidate circRNAs were significantly higher in patients with CAP than in controls (p<0.05), which was consistent with the results of the microarray analysis. Overexpression of hsa_circ_0043621 significantly increased the expression of NLRP3, induced migration of HUVECs, and inhibited cell proliferation. hsa_circ_0043621 demonstrated reasonable diagnostic accuracy for CAP detection and increased intima-media thickness (IMT). hsa_circ_0043621 upregulation was an independent predictor of an increased risk of CAP and increased IMT. CONCLUSIONS: hsa_circ_0043621 is a valuable circulating biomarker of carotid atherosclerosis and may contribute to its pathogenesis by regulating the NLRP3 inflammasome.

Associations between polymorphisms in the glucocorticoid-receptor gene and cardiovascular risk factors in a Chinese population.

BACKGROUND: Glucocorticoid is an important regulator of energy homeostasis. Glucocorticoid receptor (GR) gene polymorphisms that contribute to variability in glucocorticoid sensitivity have been identified. We explored the associations of single-nucleotide polymorphisms (SNPs) of the GR gene with traditional cardiovascular risk factors in the Chinese Han population. METHODS: We recruited 762 consecutive adults who underwent a regular physical examination at Beijing Xuanwu Hospital. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), body mass index (BMI), and waist-to-hip ratio were measured. Fourteen tag SNPs and 5 functional SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Differences between genotypes/alleles for each SNP were adjusted for sex and age and tested using a general linear model procedure. Various models of inheritance, including additive, dominant, and recessive, were tested. RESULTS: Among the 19 SNPs examined, 5 markers were associated with cardiovascular risk factors. The rs41423247 GG genotype and the rs7701443 AA genotype were associated with higher BMI and systolic blood pressure (P < 0.0004), and the rs17209251 GG genotype was associated with higher systolic blood pressure (P < 0.0004). Lower systolic blood pressure, total cholesterol, and LDL cholesterol were observed among rs10052957 A allele carriers (P < 0.0004), and lower plasma glucose and LDL-cholesterol concentrations were observed among rs2963156 TT carriers (P < 0.0004). CONCLUSIONS: Polymorphism of the GR gene was associated with cardiovascular risk factors and may contribute to susceptibility to cardiovascular disease.