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Evidence of the relationship between fecal short-chain fatty acids (SCFA) levels, dietary quality and type 2 diabetes mellitus (T2DM) in rural populations is limited. Here, we aimed to investigate the association between fecal SCFA levels and T2DM and the combined effects of dietar quality on T2DM in rural China. In total, 100 adults were included in the case–control study. Dietary quality was assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), and SCFA levels were analysed using the GC-MS system. Generalised linear regression was conducted to calculate the OR and 95 % CI to evaluate the effect of SCFA level and dietary quality on the risk of T2DM. Finally, an interaction was used to study the combined effect of SCFA levels and AHEI-2010 scores on T2DM. T2DM participants had lower levels of acetic and butyric acid. Generalised linear regression analysis revealed that the OR (95 % CI) of the highest acetic and butyric acid levels were 0·099 (0·022, 0·441) and 0·210 (0·057, 0·774), respectively, compared with the subjects with the lowest tertile of level. We also observed a significantly lower risk of T2DM with acetic acid levels > 1330·106 μg/g or butyric acid levels > 585·031 μg/g. Moreover, the risks of higher acetic and butyric acid levels of T2DM were 0·007 (95 % CI: 0·001, 0·148), 0·005 (95 % CI: 0·001, 0·120) compared with participants with lower AHEI-2010 scores (all P < 0·05). Acetate and butyrate levels may be important modifiable beneficial factors affecting T2DM in rural China. Improving dietary quality for body metabolism balance should be encouraged to promote good health. [ABSTRACT FROM AUTHOR]

To explore the independent and combined effects of ESRα methylation and progesterone on impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), a case-control study including 901 subjects was conducted. Generalized linear models were performed to assess the independent and combined effects of ESRα methylation and progesterone on IFG or T2DM. Methylation level of cytosine-phosphoguanine (CpG) 1 in the estrogen receptor α (ESRα) gene was positively related to IFG in both men (odds ratio (OR) (95% confidence interval (CI)): 1.77 (1.05, 3.00)) and postmenopausal women (OR (95% CI): 1.82 (1.09, 3.04)), whereas the association between CpG 1 and T2DM was not significant. Positive associations of progesterone with IFG and T2DM were observed in both men (OR (95% CI): 2.03 (1.18, 3.49) and 3.00 (1.63, 5.52)) and postmenopausal women (OR (95% CI): 2.13 (1.27, 3.56) and 3.30 (1.85, 5.90)). Participants with high CpG 1 methylation plus high progesterone had an increased risk of IFG and T2DM, both in men and postmenopausal women. ESRα methylation and progesterone were positively associated with IFG, and the positive association between progesterone and T2DM was also found. Importantly, we firstly found the combined effects of ESRα methylation and progesterone on IFG and T2DM. [ABSTRACT FROM AUTHOR]

There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR- P <0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P <0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure. [Display omitted] • Individual and combined exposure to various pesticides increased T2DM incidence. • MR analysis supported the causal association of pesticides with T2DM risk. • High levels of PA attenuate the diabetogenic effect of pesticides. [ABSTRACT FROM AUTHOR]

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Background: This study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China. Methods: A case–control study with 914 participants (329 T2DM, 585 controls) was conducted. Serum progesterone was detected with liquid chromatography-tandem mass spectrometry. DNA methylation of SOCS3 was determined by MethylTarget™. Linear regression was applied to evaluate the associations of progesterone and SOCS3 methylation with marks of glucose metabolism. Logistic regression was employed to investigate the independent and combined effects of progesterone and SOCS3 methylation with T2DM in men and postmenopausal women. Results: After multiple adjustment, progesterone was positively associated with T2DM in both men (odds ratio (OR) (95% confidence interval (CI)): 2.77 (1.79, 4.29)) and postmenopausal women (OR (95% CI): 1.85 (1.26, 2.72)). Methylation level of Chr17:76,356,190 or Chr17:76,356,199 (SOCS3) was negatively associated with T2DM in both men (OR (95% CI): 0.58 (0.39, 0.86) or 0.27 (0.14, 0.51)) and postmenopausal women (OR (95% CI): 0.43 (0.29, 0.65) or 0.53 (0.28, 0.99)). Subjects with high progesterone and low Chr17:76,356,190 or Chr17:76,356,199 methylation were more susceptible to have a higher prevalence of T2DM (men: OR (95% CI): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR (95% CI): 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45)). Conclusions: The independent and combined effects of progesterone and SOCS3 methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of SOCS3 could reduce the prevalence of T2DM. Trial registration The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375 [ABSTRACT FROM AUTHOR]

Background and Aim: The present study was conducted to explore the stratified and joint effects of age at menopause and body mass index (BMI) with the risk of type 2 diabetes mellitus (T2DM) in Chinese rural adults.Methods and Results: A total of 15,406 postmenopausal Chinese women were included in this study. Multivariable logistic regression analysis was used to quantify the stratified and joint effects of age at menopause and BMI on T2DM. Overall, the mean age at menopause and BMI was 48.8 ± 4.7 years and 25.1 ± 3.6 kg/m2, respectively. In general, data suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, later menopause had a higher risk of T2DM (OR, 1.52; 95% CI, 1.16-2.01); 3) the risk of T2DM was higher only in patients with early or normal age at menopause and BMI ≥ 24, with 0R (95% CI) of (1.58, 1.28-1.94) and (1.48, 1.31-1.67), respectively.Conclusion: Our findings suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, a higher risk of T2DM was found only in those with later menopause; 3) women with later menopause had a higher risk of T2DM, irrespective of BMI; 4) in patients with early or normal age at menopause, a higher risk of T2DM was found only in patients with BMI ≥ 24.the Chinese Clinical Trial Registration: ChiCTR-OOC-1500669(URL:http://www.chictr.org.cn/showproj.aspx?proj=11375). [ABSTRACT FROM AUTHOR]

Background and Aims: To assess the associations of sedentary time, suppressor of cytokine signaling (SOCS)-3 DNA methylation with type 2 diabetes mellitus (T2DM), and further identify the role of SOCS3 methylation in mediating the association of sedentary time with T2DM in a Chinese rural population.Methods and Results: A case-control study including 1032 participants from the Henan Rural Cohort study was conducted. Restricted cubic spline analysis and logistic regression model were performed to evaluate the associations between sedentary time, SOCS3 methylation and T2DM. The mediation effect of SOCS3 methylation on the association between sedentary time and T2DM was assessed. Sensitivity analysis was conducted by excluding individuals with diagnosed T2DM. Linear dose-response relationships were found between sedentary time, methylation level of Chr17:76356190 (one novel site on SOCS3) and T2DM. Compared with the first quartile (less than 5 h/d) of sedentary time, the adjusted odds ratio (OR, 95% confidence interval, 95%CI) for those in the third (7-10 h/d) and fourth (≥10 h/d) quartiles were 1.87 (1.22-2.85) and 3.54 (2.14-5.85), respectively. Participants in the fourth quartile of methylation level of Chr17:76356190 had lower risk of T2DM than those in the first quartile (OR (95%CI): 0.23 (0.14-0.38)). Mediation analysis showed 9.66% (6.38%-14.80%) of the association between sedentary time and T2DM was attributable to Chr17:76356190. The comparable effect estimates were observed between sedentary time, methylation level of Chr17:76356190 and undiagnosed T2DM.Conclusion: Sedentary time and methylation level of Chr17:76356190 were both independently associated with T2DM in the Chinese rural population. Furthermore, Chr17:76356190 appeared to partially mediate the effect of sedentary time on T2DM.Chinese Clinical Trial Registration: ChiCTR-OOC-15006699 (URL: http://www.chictr.org.cn/showproj.aspx?proj=11375). [ABSTRACT FROM AUTHOR]

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes. [Display omitted] • Individual and mixtures of OCPs exposure were positively related to T2DM risk. • Higher OCPs levels were observed to be related to lower serum testosterone levels. • A negative correlation between OCPs and androgen receptor methylation (ARm). • Testosterone and ARm plays a mediator and moderator between OCPs and T2DM. • This provides new insights into the pathways for the etiology and control of T2DM. [ABSTRACT FROM AUTHOR]

Plasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. In this study, a total of 2607 subjects aged 18–79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. The geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high‐density lipoprotein cholesterol (HDL-C) levels increased. Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM. [Display omitted] • Positive associations of various PBDE pollutants with T2DM were found in rural China. • PBDE mixtures or PBDE pollution score was positively associated with T2DM. • Higher HDL-C levels attenuated the association of PBDEs with T2DM. [ABSTRACT FROM AUTHOR]

Since neonicotinoids (NNIs) are widely used around the world, they are extensively distributed in the environment and frequently occurred in humans. This study was conducted to assess the risk of NNIs residues in vegetables and fruits in Henan province, and evaluate the associations of NNIs single and mixed exposure with glucose metabolism, and further explore whether testosterone mediated these relationships in Henan rural population. The data of vegetables and fruits were collected from Henan Province in 2020–2021, and participants were drawn from the Henan Rural Cohort study. Hazard quotient (HQ) and hazard index (HI) were used to assess the risk of exposure to the individual and combined NNIs through vegetables or fruits intake. Relative potency factor (RPF) method was utilized to normalize each NNIs to imidacloprid (IMI RPF). Generalized linear models were used to explore the effects of each NNIs and IMI RPF on glucose metabolism. Weight quartile sum (WQS) regression and Bayesian kernel machine regression (BKMR) model were applied to estimate the effect of NNIs mixtures on glucose metabolism. Mediation analysis was employed to explore whether testosterone mediated these relationships. The HQs and HI in both vegetables and fruits were much lower than 1, which indicated that NNIs in vegetables and fruits were not expected to cause significant adverse effects. However, plasma natural logarithm nitenpyram (Ln_NIT), Ln_thiacloprid-amid (Ln_THD-A), and Ln_IMI eq were positively associated with type 2 diabetes mellitus (T2DM) (odds ratio (OR) (95% confidence interval (CI)): 1.12 (1.05, 1.19), 1.21 (1.10, 1.32), and 1.48 (1.22, 1.80)). Both WQS regression and BKMR models observed significantly positive associations between NNIs mixture exposure and T2DM. Testosterone partially mediated these associations among women (PE = 6.67%). These findings suggest that human NNIs exposure may impair glucose metabolism and could contribute to rising rates of T2DM, and it's necessary to regulate the use of pesticides in rural areas. [Display omitted] • Expose to neonicotinoids (NNIs) through intake of vegetables or fruits posed a low risk to population health. • NNIs mixture exposure was positively associated with type 2 diabetes mellitus (T2DM). • Both nitenpyram and thiacloprid-amid exposure were positively associated with T2DM. • Testosterone partially mediated the association of NNIs mixture with T2DM in women. [ABSTRACT FROM AUTHOR]

Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population. To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes. After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95% CI : 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95% CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM. Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure. [Display omitted] • Several herbicides were associated with increased risk of T2DM and prediabetes. • Exposure to the mixture of herbicides was related to the increased risk of T2DM. • The impact of herbicides exposure on T2DM should be paid attention in rural adults. [ABSTRACT FROM AUTHOR]

There are increasing numbers of studies investigating the potential link between microRNAs (miRNAs) and type 2 diabetes mellitus (T2DM) risk. Based on the prior evidence and the differentially expressed candidate plasma exosome miRNAs in our established discovery study, the current meta-analysis studied miR-126 and miR-122 specifically. The purpose of the present study was to systematically and quantitatively evaluate the relationship of miR-126 and miR-22 expression level with T2DM risk as well as related glucose metabolism parameters. Moreover, the present study was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline (PRISMA 2020 statement). PubMed, Embase, Web of Science, Cochrane and Chinese National Knowledge Infrastructure electronic databases were used to identify eligible original studies prior to May 3, 2022. The random-effects models were employed to explore the overall effect estimates [odds ratio (OR) and 95% confidence interval (CI), or correlation coefficient (r, 95% CI)]. The subgroup analyses were conducted to examine the potential sources of heterogeneity. The potential publication bias was assessed by the Begg's funnel plot and Egger's tests. A total of 46 articles were included in the present meta-analysis. The results revealed that higher exposure level of miR-126 was related to lower T2DM risk in 5 analytical epidemiological studies [OR=0.73, 95% CI: (0.55, 0.96)], lower fasting blood glucose (FBG) [N=22, r=-0.26, 95% CI: (-0.42, -0.10)], and lower homeostasis model assessment of insulin resistance (HOMA-IR) index [N=9, r=-0.28, 95% CI: (-0.52, -0.05)]. Besides, positive correlations were observed between miR-122 expression and FBG [N=10, r=0.34, 95% CI: (0.20, 0.48)], as well as HOMA-IR index [N=9, r=0.40, 95% CI: (0.16, 0.64)]. The relationship of miR-126 and miR-122 expression with T2DM risk and these glucose metabolism parameters may be influenced by study types, sample size, different source and mean age of participants. In conclusion, in the general healthy population, higher miR-126 expression was related to lower T2DM risk, FBG level and HOMA-IR index; higher miR-122 expression was closely correlated with higher FBG level and HOMA-IR index. These findings have notable clinical and public health implications for screening and control glucose metabolic disorders, insulin resistance and T2DM development. [ABSTRACT FROM AUTHOR]

Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D3, 25(OH)D2, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D2 and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D3 was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p < 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D2 or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D2, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive <0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D2 was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone. [ABSTRACT FROM AUTHOR]

Recent studies on whether dairy consumption is associated with type 2 diabetes mellitus (T2DM) have yielded inconsistent results, so we explored the relationship between dairy consumption and T2DM through a large-sample, cross-sectional study and a meta-analysis. In the meta-analysis, summary relative risks (RRs) of 23 articles were compiled with a random effects model, and a restricted cubic spline regression model was used to explore whether there is a nonlinear relationship between dairy intake and T2DM risk. This cross-sectional study used baseline data from 38,735 participants of the Henan Rural Cohort study and the association between dairy consumption and T2DM was analyzed by a logistic regression model. The meta-analysis revealed a borderline negative significant association between total dairy intake and risk of T2DM, the RR and 95% confidence interval (CI) was 0.94; (0.89, 1.00), and the risk was lowest at 270 g daily dairy intake. In the cross-sectional study, there were 3654 T2DM patients and 68.3 percent of the respondents had no dairy intake. The average intake of dairy in the total population was 12 g per day. Fully adjusted analyses suggested positive associations, with an odds ratio (OR) comparing the highest with the zero intake of 1.34 (95% CI: 1.22, 1.48) for all participants, which was unaffected by sex. Dairy intake in rural areas of Henan province is low, and we found, in the context of overall low dairy intake, that a high intake was positively associated with T2DM, which is inconsistent with the meta-analysis results suggesting that dairy has marginal protective effects against T2DM. [ABSTRACT FROM AUTHOR]

• There is a positive correlation between isofenphos, isocarbophos levels with T2DM. • Isofenphos and isocarbophos significantly increased the risk of T2DM. • The association may be mediated by WBC and NE. To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the association of serum testosterone with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) and calculate the proportion explained by obesity status on the relationship.Materials and Methods: A case-control study including 2775 participants was performed. Serum testosterone was quantified by liquid chromatography-tandem mass spectrometry. Conditional logistic regression and multivariable linear regression were performed to estimate the relationships between testosterone and different glucose status. Waist circumference (WC) was used as a mediator to estimate the mediation effect.Results: After adjusting for multiple variables, serum testosterone levels were negatively associated with T2DM in males (per 1 unit natural log-transformed, odd ratio (OR) = 0.73, 95% confidence interval (CI): 0.56, 0.96; Tertile 3 vs Tertile 1, OR = 0.46, 95% CI:0.29, 0.72) while were positively in females (per 1 unit natural log-transformed, OR = 1.56, 95% CI:1.32, 1.84; Tertile 3 vs Tertile 1, OR = 3.55, 95% CI: 2.22, 5.66). In males, a higher testosterone tended to be associated with a lower fasting plasma glucose level and a weaker HOMA2-IR but a stronger HOMA2-β. Opposite findings were observed in females. Furthermore, WC played a full and partial mediating role in the relationship between testosterone and IFG and T2DM both in males and females.Conclusion: Serum testosterone levels had opposite effects on IFG and T2DM in males and females. With higher serum testosterone levels, the dysglycemia progression was decreased among males while increased among females. In addition, WC played a full and partial mediating role in the relationship between testosterone and IFG and T2DM. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the independent and combined dose-response association of napping and night sleep duration with type 2 diabetes mellitus (T2DM) among different genders in the rural Chinese population.Methods: For this research, a total of 19,257 participants were enrolled in the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study. Napping and night sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). Restricted cubic splines and logistic regression were used to estimate the relationship between napping and night sleep duration with T2DM.Results: A linear dose-response relationship between napping duration and T2DM as well as a U-shaped relationship between night sleep duration and T2DM were found. Compared with those who reported no napping, participants who had a napping duration of ≥91 min were associated with a 19% increase in prevalence of T2DM. Adjusted odds ratios (ORs) (95% confidence intervals (CIs)) for T2DM were 1.48 (1.03, 2.14) and 1.50 (1.22, 1.85) for shorter (≤5 h) and longer (>9 h) night sleep duration compared with the referential group. Additionally, the combination of longer napping duration (≥91 min) and night sleep duration (>9 h) increased 104% (95% CI: 45%, 128%) prevalence for T2DM. These associations were not found in males but were evident in females.Conclusions: Longer napping duration and extreme night sleep duration increased the prevalence of T2DM. Meanwhile, longer napping and night sleep duration might be jointly associated with a higher prevalence of T2DM. [ABSTRACT FROM AUTHOR]

Parabens, a widely exposed environmental endocrine disruptor, were reported to disturb glucose metabolism through various pathways in animal models, but epidemiologic studies are limited. Therefore, this study aimed to investigate the plasma parabens level in rural populations and their effects of single and mixed paraben exposure on T2DM based on the Henan Rural Cohort. A total of 1713 participants (880 T2DM and 833 controls) from the Henan Rural Cohort Study were included in this case-control study. Generalized linear regression models were performed to assess the single and joint effects of parabens on T2DM and glucose metabolism indicators. In addition, the dose-response relationship of plasma parabens with T2DM and glucose metabolism indicators were explored by the restricted cubic splines. Bayesian kernel machine regression (BKMR) and quantile g-computation models were utilized to assess overall associations of paraben mixtures with T2DM and glucose metabolism indicators. Σparabens and methylparaben (MeP) exposure significantly increased the risk of T2DM (P < 0.01). However, ethylparaben (EtP) and butylparaben (BuP) were negatively related to T2DM (P < 0.01). Notably, non-linear relationships of EtP and BuP with T2DM were observed. When the level of EtP or BuP was above the inflection point observed in dose-response curve, the ORs and 95% CIs were 1.453 (1.252, 1.686) and 1.982 (1.444, 2.721), respectively. Moreover, the result of quantile g-computation also showed that exposure to high concentration of parabens mixture was positively related to the risk of T2DM. BKMR model indicated that parabens mixture was associated with glycometabolism following a U-shape and parabens mixture increased the risk of dysglycemia when all parabens concentrations were at or above their 55th percentile compared with the median. MeP or paraben mixture exposure levels showed a linear positive association with risk of T2DM. EtP and BuP were nonlinearly associated with glucose metabolism and moderate-high exposure contributed to T2DM. [Display omitted] • Various models were used to evaluate effects of parabens' single and mixed exposure. • Methylparaben and parabens mixture exposure may increase the risk of dysglycemia. • Ethylparaben and Butylparaben were nonlinearly associated with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to examine the association of T2DM/PDM risk with single OPP exposure and multi-OPP co-exposure. Plasma levels of ten OPPs were measured using the gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) among 2734 subjects from the Henan Rural Cohort Study. We used generalized linear regression to estimate odds ratios (OR s) or β with 95% confidence intervals (CI s), and constructed quantile g-computation and Bayesian kernel machine regression (BKMR) models to investigate the association of OPPs mixture with the risk of T2DM and PDM. High detection rates ranged from 76.35% (isazophos) to 99.17% (malathion and methidathion) for all OPPs. Several plasma OPPs concentrations were in positive correlation with T2DM and PDM. Additionally, positive associations of several OPPs with fasting plasma glucose (FPG) values and glycosylated hemoglobin (HbA1c) levels were observed. In the quantile g-computation, we identified significantly positive associations between OPPs mixtures and T2DM as well as PDM, and fenthion had the greatest contribution for T2DM, followed by fenitrothion and cadusafos. As for PDM, the increased risk was largely explained by cadusafos, fenthion, and malathion. Furthermore, BKMR models suggested that co-exposure to OPPs was linked to an increased risk of T2DM and PDM. Our findings suggested that the individual and mixture of OPPs exposure were associated with an increased risk of T2DM and PDM, implying that OPPs might act an important role in the development of T2DM. [Display omitted] • OPPs mixtures were positively associated with the risk of T2DM and PDM among Chinese population. • We utilized the quantile g-computation and BKMR models to analyze the joint effects of co-exposure OPPs mixtures. • Main contributors included fenthion, fenitrothion, cadusafos, and malathion. • Several OPPs were significantly associated with elevated FPG and HbA1c levels. [ABSTRACT FROM AUTHOR]

As the major vitamin D binding protein (DBP), the group-specific component (GC) plays an important role in the bioactivity of vitamin D. Abnormal expression of GC gene may be associated with vitamin D related disease, type 2 diabetes mellitus (T2DM). DNA methylation is an important regulator of gene expression. It has been reported that methylation in 3′ untranslated region played a role in regulation of protein expression via interaction with miRNA. This study hypothesized that DNA methylation of 3′ near region of GC gene ( 3 ′ GC ) might be associated with T2DM. The methylation status of the 3 ′ GC was assessed with high resolution melt method. Logistic regression was applied to assess the risk of T2DM at different levels of 3′ GC methylation. The results showed that methylation level of the 3 ′ GC was higher in T2DM patients than in non-T2DM individuals ( P = .038). There was a significant association between 3 ′ GC methylation level and T2DM (adjusted OR 1.282; 95% CI 1.062–1.548; P = .01). The association was independent upon serum glucose and insulin (adjusted OR 1.561; 95% CI 1.083–2.249; P = .017). Furthermore, there was a positive correlation between methylation level and the level of DBP in T2DM patients ( r = 0.126, P = .036). The association was also significant after adjusting the potential impact of rs705117 ( P = .044). Besides, a positive correlation between methylation level and the level of fasting serum insulin was observed in non-T2DM ( r = 0.101, P < .001). These results suggest that methylation status of the 3 ′ GC is most likely associated with DBP expression, insulin secretion, and T2DM. [ABSTRACT FROM AUTHOR]

Aims: Association between T2DM and vitamin D was found in many epidemiologic reports. And 24-hydroxylase encoded by CYP24A1 is the very enzyme that degrades the active vitamin D metabolite. We aimed to investigate the association between rs4809957 in CYP24A1 and T2DM, as well as vitamin D level.Methods: A total of 419 pedigrees containing 1556 participants were included. T2DM diagnosis, 25(OH)D measurement and genotyping of rs4809957 were conducted for all the individual. Then association between rs4809957 and T2DM, as well as 25(OH)D level, was investigated by family-based association test (FBAT) and 1:1 matched case-control study.Results: The FBAT results revealed that there was transmission disequilibrium for allele G in T2DM families by both additive model (Z = 2.183, P = 0.029049) and recessive model (Z = 2.236, P = 0.025347). Allele G was also associated with 25(OH)D level in both additive model (Z = 2.549, P = 0.010811) and dominant model (Z = 2.012, P = 0.044187). On the other hand, results of case-control study suggested that vitamin D deficiency was a risk factor for T2DM (OR 1.987; 95%CI 1.331-2.964; P = 0.001). Further stratified analysis revealed that vitamin D deficiency increased T2DM risk in women (OR 2.347; 95%CI 1.373-4.012; P = 0.002), instead of men (OR 1.600; 95%CI 0.874-2.931; P = 0.127). In addition, T2DM patients with GG and AG genotypes were more susceptible to vitamin D deficiency than the control (P = 0.006 and P = 0.038, respectively).Conclusion: There was transmission disequilibrium for allele G of rs4809957 in T2DM families, which was linked to vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Obesity and ambient air pollution are independent risk factors of type 2 diabetes mellitus (T2DM), however, the evidence regarding their joint associations on T2DM was sparsely studied in low-middle income countries. A total of 38,841 participants were selected from Henan Rural Cohort study which was carried out during 2015–2017. Obesity was identified by body mass index (BMI), WC (waist circumstance), WHR (waist-to-hip ratio), WHtR (waist-to-height ratio), BFP (body fat percent), and VFI (visceral fat index). Three-year averaged-concentrations of NO 2 , PM 1 , PM 2.5 , and PM 10 were assessed by using the method of spatiotemporal model incorporated into the satellites data. The independent associations of obesity indicators and exposure to air pollutants on fasting blood glucose (FBG) and T2DM were assessed by generalized linear and logistic regression model, respectively, and their interaction associations on T2DM were quantified by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Positive associations of six obesity measures and four air pollutants with FBG levels and prevalent T2DM were observed. Obese participants measured by BMI plus high exposure to NO 2 , PM 1 , PM 2.5 and PM 10 were related to a 2.96-fold (2.66–3.29), 2.87-fold (2.58–3.20), 2.98-fold (2.67–3.32) and 3.01-fold (2.70–3.35) increased risk for prevalent T2DM, respectively; similarity of joint associations of the other obesity measures and air pollutants on T2DM were observed. The additive associations of different obesity measures and air pollutants with prevalent T2DM were further found. The synergistic associations of obesity and air pollutants on FBG levels and prevalent T2DM were observed, indicating that obese participants were at high risk for prevalent T2DM in highly polluted rural regions. [Display omitted] • Comprehensive assessment of association between obesity and T2DM were conducted. • Joint associations of obesity and air pollutants on T2DM were explored. • Both obesity and exposure to high air pollutants were related to prevalent T2DM. • Obese individuals were more susceptible to prevalent T2DM in highly polluted areas. [ABSTRACT FROM AUTHOR]

Aims: We aimed to evaluate the associations of mineralocorticoids with type 2 diabetes mellitus (T2DM) and glucose homeostasis among rural Chinese adults.Methods: A total of 2713 participants were selected from the Henan Rural Cohort study. Serum mineralocorticoids were measured by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were employed to evaluate the associations of mineralocorticoids with pre-diabetes and T2DM. Linear regression was implemented to assess the associations of aldosterone and 11-deoxycorticosterone with different markers of glucose homeostasis by different diabetes status.Results: Elevated aldosterone and 11-deoxycorticosterone were associated with an increased prevalence of pre-diabetes and T2DM (P < 0.05), with a nonlinear dose-response trend, but the association between 11-deoxycorticosterone and T2DM was no statistical significance after adjustment. A 100% increase in ln-aldosterone was associated with a 0.029 mg/dl higher fasting plasma glucose (FPG) and a 1.2% higher HOMA2-IR among those with normal glucose tolerance (NGT), and related to a 0.034 mg/dl lower FPG, a 1.1% higher HbA1c and a 1.3% higher HOMA2-β among individuals with pre-diabetes. A 100% increment in ln-11-deoxycorticosterone was associated with a 16% increase in HbA1c and a 5.6% decrease in HOMA2-β in participants with T2DM.Conclusions: Higher aldosterone and 11-deoxycorticosterone are associated with T2DM risk and glucose homeostasis disorder among different diabetes status. [ABSTRACT FROM AUTHOR]