Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones.

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.

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population.

BACKGROUND: Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men. MATERIALS AND METHODS: This cross-sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography-tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity. RESULTS: After adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high-sensitivity C-reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high-sensitivity C-reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist-to-hip ratio), 12.92% (defined by waist-to-height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity. CONCLUSION: Inflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases.

Exposure to herbicides mixtures in relation to type 2 diabetes mellitus among Chinese rural population: Results from different statistical models.

BACKGROUND: 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. AIMS: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Co-exposure of organophosphorus pesticides is associated with increased risk of type 2 diabetes mellitus in a Chinese population.

OBJECTIVE: 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. METHODS: 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 (ORs) or ß with 95% confidence intervals (CIs), 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. RESULTS: 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. CONCLUSION: 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.

Serum Progesterone is Negatively Associated with Hypertension and Blood Pressure Indicators Among Men and Postmenopausal Women.

Sex hormones have been shown to be negatively associated with hypertension, but the relationship between serum progesterone levels and hypertension has not been adequately studied. Therefore, we aimed to evaluate the association between progesterone and hypertension among Chinese rural adults. A total of 6222 participants were recruited, which included 2577 men and 3645 women. The concentration of serum progesterone was detected by liquid chromatography-mass spectrometer system (LC-MS/MS). Logistic regression and linear regression were used to assess the associations between progesterone levels and hypertension and blood pressure related indicators, respectively. Constrained splines were used to fit the dose-response relationships of progesterone with hypertension and blood pressure related indicators. Moreover, the interactive effects of several lifestyle factors and progesterone were identified by a generalized linear model. After fully adjusting the variables, progesterone levels were inversely associated with hypertension in men [odds ratio (OR): 0.851, 95% confidence interval (CI): 0.752, 0.964]. Among men, a 2.738 ng/ml increase in progesterone was associated with a 0.557 mmHg decrease in diastolic blood pressure (DBP) (95% CI: -1.007, -0.107) and a 0.541 mmHg decrease in mean arterial pressure (MAP) (95% CI: -1.049, -0.034), respectively. Similar results were observed in postmenopausal women. Interactive effect analysis showed that only a significant interaction was observed between progesterone and educational attainment on hypertension in premenopausal women (p=0.024). Elevated levels of serum progesterone were associated with hypertension in men. Except for premenopausal women, a negative association of progesterone with blood pressure related indicators was observed.

Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020.

Background: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province. Methods: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions. Results: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) (P < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all P < 0.05). Conclusion: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management.