Associations of serum glucocorticoid levels on hypertension and blood pressure-related indicators: a nested case-control study in rural China.

BACKGROUND: The relationship between glucocorticoids and hypertension has shown inconsistent findings in previous studies. To address this, our study employed a nested case-control design in rural areas to further investigate the association between serum glucocorticoid levels and hypertension, and blood pressure-related indicators. METHODS: This study employed a nested case-control design, involving 560 pairs of hypertensive cases and matched controls. The concentrations of serum cortisol (F), cortisone (E) and 11-deoxycortisol (S) were determined using liquid chromatography-tandem mass spectrometry. We employed various methods, including generalized linear model (GLM), conditional logistic regression model, restricted cubic spline regression, subgroup analysis, interaction, and joint effects, with adjustments for multiple covariates to analyze the relationships between glucocorticoids, hypertension, and blood pressure-related indicators. RESULTS: After multivariable adjustments, ln-F, ln-F/E, and ln-S were positively associated with SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP), while ln-E was negatively associated with DBP and MAP (P < 0.05). Interestingly, ln-S showed no statistically significant association with hypertension prevalence (P > 0.05), whereas ln-F and ln-F/E were positively associated with it (P < 0.05). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.153 (1.011-1.315) for ln-F and 2.072 (1.622-2.645) for ln-F/E, respectively. In contrast, ln-E exhibited a negative association with hypertension prevalence (adjusted OR = 0.837, 95% CI 0.714-0.982). Moreover, a significant association was observed between the combined use of high-dose F/E and high-dose S with hypertension prevalence (adjusted OR = 3.273, 95% CI 2.013-5.321). Blood pressure indicators and hypertension prevalence significantly increased with elevated serum F and F/E concentrations (P < 0.05). Interaction analysis further revealed that among women, the positive association between F/E and hypertension prevalence was more pronounced than in men (P < 0.05), and S exhibited a more significant positive association with hypertension prevalence in the overweight population (P < 0.05). CONCLUSION: Serum F/E and S levels demonstrated positive associations with hypertension and blood pressure-related indicators, and their combined influence exhibited a synergistic effect on hypertension. Notably, F, F/E, and S were associated with heightened hypertension risk, warranting particular attention in women and overweight populations.

Association of short-chain fatty acids and the gut microbiome with type 2 diabetes: Evidence from the Henan Rural Cohort.

BACKGROUND AND AIMS: Human studies about short-chain fatty acids (SCFAs), the gut microbiome, and Type 2 diabetes (T2DM) are limited. Here we explored the association between SCFAs and T2DM and the effects of gut microbial diversity on glucose status in rural populations. METHODS AND RESULTS: We performed a cross-sectional study from the Henan Rural Cohort and collected stool samples. Gut microbiota composition and faecal SCFA concentrations were measured by 16S rRNA and GC-MS. The population was divided based on the tertiles of SCFAs, and logistic regression models assessed the relationship between SCFAs and T2DM. Generalized linear models tested the interactions between SCFAs and gut microbial diversity on glucose indicators (glucose, HbAlc and insulin). Compared to the lowest tertile of total SCFA, acetate and butyrate, the highest tertile exhibited lower T2DM prevalence, with ORs and 95% CIs of 0.291 (0.085-0.991), 0.160 (0.044-0.574) and 0.171 (0.047-0.620), respectively. Restricted cubic spline demonstrated an approximately inverse S-shaped association. We also noted interactions of the ACE index with the highest tertile of valerate on glucose levels (P-interaction = 0.022) and the Shannon index with the middle tertile of butyrate on insulin levels (P-interaction = 0.034). Genus Prevotella_9 and Odoribacter were inversely correlated with T2DM, and the genus Blautia was positively associated with T2DM. These bacteria are common SCFA-producing members. CONCLUSIONS: Inverse S-shaped associations between SCFAs (total SCFA, acetate, and butyrate) and T2DM were observed. Valerate and butyrate modify glucose status with increasing gut microbial diversity.

New findings on the risk of hypertension from organophosphorus exposure under different glycemic statuses: The key role of lipids?

BACKGROUND AND OBJECTIVE: Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different glycemic statuses may respond differently to the biological effects of OPs. Therefore, this study, based on the Henan rural cohort, aims to investigate the association between OPs exposure and HTN, and further explores whether lipids mediate these associations. METHODS: We measured the plasma levels of OPs in 2730 participants under different glycemic statuses using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). A generalized linear model, Quantile g-computation (QGC), adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) models were used to assess the impact of OPs exposure on HTN, with least absolute shrinkage and selection operator (LASSO) penalty regression identifying main OPs. Mediation models were used to evaluate the intermediary role of blood lipids in the OPs-HTN relationship. RESULTS: The detection rates for all OPs were high, ranging from 76.35 % to 99.17 %. In the normal glucose tolerance (NGT) population, single exposure models indicated that malathion and phenthoate were associated with an increased incidence of HTN (P-FDR < 0.05), with corresponding odds ratios (ORs) and 95 % confidence intervals (CIs) of 1.624 (1.167,2.260) and 1.290 (1.072,1.553), respectively. QGC demonstrated a positive association between OP mixtures and HTN, with malathion and phenthoate being the primary contributors. Additionally, the AENET model's Exposure Response Score (ERS) suggested that the risk of HTN increases with higher ERS (P < 0.001). Furthermore, BKMR revealed that co-exposure to OPs increases HTN risk, with phenthoate having a significant impact. Furthermore, triglycerides (TG) mediated 6.55 % of the association between phenthoate and HTN. However, no association was observed in the impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) populations. CONCLUSIONS: Our findings suggest that in the NGT population, OPs may significantly contribute to the development of HTN, proposing TG as a potential novel target for HTN prevention.

Association of the short-chain fatty acid levels and dietary quality with type 2 diabetes: a case-control study based on Henan Rural Cohort.

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.

Association of low-carbohydrate diet scores and type 2 diabetes in Chinese rural adults: The Henan Rural Cohort Study.

PURPOSE: To investigate the association between low-carbohydrate diet scores (LCDs) and the risk of type 2 diabetes in rural China. METHODS: A total of 38,100 adults were included in the Henan Rural Cohort Study. Macronutrient intake was assessed via a validated food-frequency questionnaire to create low-carbohydrate diet (LCD) scores. Multivariate logistic regression models and subgroup analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: After multivariable adjustment, participants with a high total low-carbohydrate diet score have a high risk of T2D (extreme-quartile OR = 1.23, 95% CI: 1.04-1.41; P = 0.007), whereas plant-based LCD score is not related to T2D risk. Among individuals with a BMI < 24 (extreme-quartile OR = 1.22, 95% CI: 1.01-1.47; P < 0.001) or high levels of physical activity (extreme-quartile OR = 1.42, 95% CI: 1.17-1.72; P < 0.001), the animal-based LCD score is positively correlated with the risk of T2D. CONCLUSION: Among Chinese rural populations, high-fat-low carbohydrate diet is associated with an increased risk of type 2 diabetes. High intake of animal protein and fat also increases T2D risk in those who are overweight or have high physical activity.

The relationship between cooking fuel use and sex hormone levels: A cross-sectional study and Mendelian randomization study.

PURPOSE: The aim of this study was to investigate the effect of solid fuel use on serum sex hormone levels. Furthermore, the effects of improved kitchen ventilation and duration of cooking time on the relationship between solid fuel use and serum sex hormone levels will be further explored. METHODS: In this cross-sectional study, 5386 individuals were recruited. Gender and menopausal status modified associations between solid fuel type and serum sex hormone levels was investigated through generalized linear models and further analyzed by improving kitchen ventilation and length of cooking time on the relationship between solid fuel use and serum sex hormone levels. To identify the causal association, mendelian randomization of two-sample was performed. RESULTS: In observational analyses, for ln-17-hydroxyprogesterone, ln-testosterone, and ln-androstenedione among premenopausal women, the estimated ß and 95 % CI of sex hormone levels for the effect of solid fuel users was -0.337 (-0.657, -0.017), -0.233 (-0.47, 0.005), and - 0.240 (-0.452, -0.028) respectively, and - 0.150 (-0.296, -0.004) in ln-progesterone among postmenopausal women. It was found that combining solid fuels with long cooking periods or no ventilation more effectively reduced testosterone and androstenedione in premenopausal women. We further found the adverse effects of using solid fuel on progesterone, testosterone, and androstenedione levels were enhanced with the increases of PM1, PM2.5, PM10, and NO2. Corresponding genetic, the causal risk effect of solid fuel were - 0.056 (-0.513, 0.4) and 0.026 (-3.495, 3.547) for testosterone levels and sex hormone binding globulin, respectively. CONCLUSION: Using gas or solid fuel was negatively related to sex hormone levels. A combination of using solid fuels, cooking for a long time, or cooking without ventilation had a stronger effect on sex hormone levels. However, genetic evidence did not support causality for the associations. WHAT IS ALREADY KNOWN ON THIS TOPIC?: The mechanisms underlying these associations household air pollution (HAP) from incomplete combustion of such fuels and occurrence of chronic diseases remained obscure. Recent years, extensive evidences from animal as well as human researches have suggested that progestogen and androgen hormones are involved in the development of diabetes, hypertension, and cardiovascular disease, which indicated that changes in serum progestogen and androgen hormones levels might play a role in these pathological mechanisms. However, limited evidence exists examining the effect of HAP from solid fuel use on serum sex hormone levels.

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.

Associations of Long-Term Exposure to PM2.5 and Its Constituents with Erythrocytosis and Thrombocytosis in Rural Populations.

Evidence on the effect of long-term exposure to fine particulate matter (PM2.5) on erythrocytosis and thrombocytosis prevalence was limited. We aimed to investigate the association of PM2.5 and its constituents with the risks of erythrocytosis and thrombocytosis. The present study included a total of 33,585 participants from the Henan Rural Cohort at baseline between 2015 and 2017. A hybrid satellite-based model was employed to estimate the concentrations of PM2.5 mass and its constituents (including black carbon [BC], nitrate [NO3-], ammonium [NH4+], inorganic sulfate [SO42-], organic matter [OM], and soil particles [SOIL]). The logistic regression model was used to assess the associations of single exposure to PM2.5 and its constituents with the risks of erythrocytosis and thrombocytosis, and the quantile G-computation method was applied to evaluate their joint exposure risk. For the independent association, the odds ratios for erythrocytosis/thrombocytosis with 1 µg/m3 increase was 1.049/1.043 for PM2.5 mass, 1.596/1.610 for BC, 1.410/1.231 for NH4+, 1.205/1.139 for NO3-, 1.221/1.359 for OM, 1.300/1.143 for SO42-, and 1.197/1.313 for SOIL. Joint exposure to PM2.5 and its components was also positively associated with erythrocytosis and thrombocytosis. The estimated weight of NH4+ was found to be the largest for erythrocytosis, while OM had the largest weight for thrombocytosis. PM2.5 mass and its constituents were positively linked to prevalent erythrocytosis and thrombocytosis, both in single-exposure and joint-exposure models. Additionally, NH4+/OM was identified as a potentially responsible component for the association between PM2.5 and erythrocytosis/thrombocytosis.

Exposure Profile and Characteristics of Parabens and Alkylphenols in Plasma among Rural Adults in Central China.

Parabens and alkylphenols pose serious hazards to human health, yet there are few studies on their exposure profiles and health risks in rural Chinese populations. In this study, 804 participants were selected from the Henan Rural Cohort in mid-eastern China. The plasma levels of parabens (methylparaben, ethylparaben, propylparaben, butylparaben (BuP)) and alkylphenols (4-tert-butylphenol (4-t-BP), 4-tert-octylphenol (4-t-OP)) were analyzed via liquid chromatography-tandem mass spectrometry. Linear regression models were used to investigate factors that may influence pollutant exposure levels. The correlation between contaminants was assessed using Spearman's correlation. The human contaminant intake was estimated using the estimated daily intake (EDI). The health risk was assessed using the hazard quotient (HQ). The detection frequency of four parabens and two alkylphenols exceeded 75%, with median concentrations of 0.444, 0.067, 0.078, 0.053, 8.810, and 6.401 ng/mL, respectively. Significant correlations were observed between parabens, as well as between 4-t-BP and 4-t-OP. Regarding gender, paraben concentrations were higher in women than in men, except for BuP. The EDI for pollutants except 4-t-OP was lower than their respective tolerable/acceptable daily intake. In total, 85.70% of participants had 4-t-OP HQ > 1. A widespread exposure to parabens and alkylphenols among the rural population was found. The high health risks of alkylphenol exposure indicate that alkylphenols should be used with caution.

Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

Exposure to parabens and dysglycemia: Insights from a Chinese population.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Health risks of neonicotinoids chronic exposure and its association with glucose metabolism: A case-control study in rural China.

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 (IMIRPF). Generalized linear models were used to explore the effects of each NNIs and IMIRPF 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_IMIeq 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.

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.

Synergistic association of long-term ozone exposure and solid fuel use with biomarkers of advanced fibrosis.

This study aims to explore the association of combined exposure to cooking fuel type and ambient ozone (O3) levels with hepatic fibrosis indices among rural adults. A total of 21,010 participants were derived from the Henan Rural Cohort. Information regarding cooking fuel type was collected through a questionnaire, and the concentration of ground-level O3 for each subject was obtained from the Tracking Air Pollution in China (TAP) dataset. A generalized linear model was used to examine the independent association of cooking fuel type or O3 exposure with hepatic fibrosis indices (FIB-4, APRI, and AST/ALT), and their possible interactions with advanced fibrosis were conducted. Compared to clean fuel users, solid fuel users had increased the risk of advanced fibrosis, the adjusted odds ratio (OR) of its assessment by FIB-4 1.240 (1.151, 1.336), by APRI 1.298 (1.185, 1.422), and by AST/ALT 1.135 (1.049, 1.227), respectively. Compared to low O3 exposure, the adjusted ORs of advanced fibrosis assessed by FIB-4, APRI, and AST/ALT in women with high O3 exposure were correspondingly 1.219 (1.138, 1.305), 1.110 (1.017, 1.212), and 0.883 (0.822, 0.949). The adjusted ORs of advanced fibrosis assessed by FIB-4, APRI, and AST/ALT for solid fuel users with high O3 exposure relative to clean fuel users with low O3 exposure in women were 1.557 (1.381, 1.755), 1.427 (1.237, 1.644), and 0.979 (0.863, 1.108), respectively. Significant additive effect of O3 exposure and solid fuel use on FIB-4-defined advanced fibrosis was observed in women, which was quantified by RERI (0.265, 95%CI: 0.052, 0.477), AP (0.170 95%CI: 0.045, 0.295), and SI (1.906, 95%CI: 1.058, 3.432). Solid fuel users with high O3 exposure were significantly associated with elevated hepatic fibrosis indices among rural women, suggesting that poor air quality may induce hepatocellular injury, and women might be more vulnerable to air pollution. The findings indicate that using cleaner fuels in cooking is an effective measure to maintain sustainable development of the environment and gain beneficial effect on human health. Clinical trial registration: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375.

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.

Combined Effects of ESRα DNA Methylation and Progesterone on Glucose Metabolic Disorders: The Henan Rural Cohort Study.

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.

The association of cortisol/testosterone ratio and sleep quality with coronary heart disease: A case-control study in Chinese rural population.

PURPOSE: There were limited studies that have probed into the combined effect of the cortisol/testosterone (C/T) ratio as a biomarker of stress and Pittsburgh Sleep Quality Index (PSQI) on coronary heart disease (CHD). This research aimed to explore the association of C/T ratio and PSQI with the risk of CHD in a rural Chinese population, as well as the interaction and combined effect between C/T ratio and PSQI on CHD. METHODS: A case-control study was performed including 307 individuals without CHD and 307 patients drawn from Henan Rural Cohort. Logistic regression was utilized to survey the independent and joint effects of the C/T ratio and PSQI on CHD. To estimate the interaction impact of the C/T ratio and sleep quality (PSQI) on CHD, a cross-product term was introduced in the generalized linear model. RESULTS: Higher C/T ratio and PSQI index scores are related to increased odds ratio for CHD (Odds ratios (ORs) and 95 % confidence interval (CI) were 1.17 (1.07, 1.29), p-trend < 0.001; 1.16 (1.09, 1.22), respectively). The odds ratio of C/T ratio for CHD increased with increasing PSQI in women (pinteraction = 0.018) and total population (pinteraction = 0.033). The combined group of high C/T ratio and high PSQI had the highest risk of CHD (Total: OR = 7.53, 95 % CI: 4.12-13.76). CONCLUSIONS: The risk of CHD was associated with low testosterone levels, high C/T ratios, and high PSQI scores. Additionally, poor sleep quality aggravated the effect of high C/T ratio on coronary heart disease.

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.