Search

Background: Endocrine function in patients with type 2 diabetes (T2DM) typically differs from those with normal glucose tolerance (NGT). However, few epidemiologic studies have explored how these differences impact the association between exposure to polychlorinated biphenyls (PCBs) and vitamin D levels. Methods: This study included 1,705 subjects aged 18–79 years from the Henan Rural Cohort [887 NGT and 818 T2DM]. Linear regression was applied to evaluate the associations between PCB exposure and vitamin D levels. Quantile g-computation regression (QG) and Bayesian kernel machine regression (BKMR) were applied to evaluate the impact of PCB mixtures on vitamin D levels. Interaction effects of ΣPCBs with HOMA2-%β and HOMA2-IR on vitamin D levels were assessed. Results: Plasma ΣPCBs was positively associated with 25(OH)D2 in the NGT group (β = 0.060, 95% CI: 0.028, 0.092). Conversely, in T2DM group, ΣPCBs was negatively associated with 25(OH)D3 and 25(OH)D (β = -0.049, 95% CI: -0.072, -0.026; β = -0.043, 95% CI: -0.063, -0.023). Similarly, both QG and BKMR analysis revealed a negative association between PCB mixture exposure and vitamin D levels in the T2DM group, contrary to the results observed in the NGT groups. Furthermore, the negative association of ΣPCBs with 25(OH)D2 and 25(OH)D disappeared or changed to a positive association with the increase of HOMA2-%β levels. Conclusions: These findings suggest that decreased β cell function may exacerbate the negative effects of PCB exposure on vitamin D levels. Recognizing T2DM patients' sensitivity to PCBs is vital for protecting chronic disease health. [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]

Increasing evidence suggested that the expression and inter-regulation of long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) were related to the development of diabetes. Based on bioinformatics analysis, this study aimed to comprehensively analyze the dysregulated RNA molecules related to new-onset type 2 diabetes mellitus (T2DM). Twenty-four patients with new-onset T2DM were included as cases, and sex- and age-matched participants were included as controls. The differentially expressed lncRNAs, miRNAs, and mRNAs between the two groups were screened by RNA sequencing. LncRNA-miRNA-mRNA network and enrichment analysis were used to reveal the RNA molecules that were potentially associated with T2DM and their early changes. A total of 123 lncRNAs, 49 miRNAs, and 312 mRNAs were differentially expressed in the new-onset T2DM (fold change ≥ 1.5 and p value < 0.05). Functional analysis revealed that differentially expressed RNAs were likely to play essential roles in diabetes-related pathways. In addition, the protein–protein interaction (PPI) network screened multiple hub mRNAs, and lncRNA-miRNA-mRNA networks showed that a single miRNA could be related to multiple lncRNAs, and then they coregulated more mRNAs. SLC25A4, PLCB1, AGTR2, PRKN, and SCD5 were shown to be important mRNAs in T2DM, and miR-199b-5p, miR-202-5p, miR-548o-3p as well as miR-1255b-5p could be involved in their regulation. In conclusion, several new and previously identified dysregulated lncRNAs, miRNAs, and mRNAs were found to be vital biomarkers in T2DM. Their alterations and interactions could modulate the pathophysiology of T2DM. Those findings may provide new insights into the molecular mechanisms underlying the development of 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]

Background and Aims. The effects of cortisol on cardiovascular diseases (CVD) and CVD risk are unknown, especially in patients with type 2 diabetes mellitus (T2DM). Furthermore, it is unclear whether 25 (OH)D can alter the associations of cortisol with CVD and CVD risk factors. Thus, the present study was to investigate the associations of serum cortisol with CVD and CVD risk factors and whether 25 (OH)D altered these associations among patients with T2DM. Materials and methods. A total of 762 patients diagnosed with T2DM were recruited. The levels of serum cortisol and 25 (OH)D were measured with a liquid chromatography-tandem mass spectrometry. Logistic regression and linear regression were used to assess the association of cortisol with CVD and multiple cardiovascular risk factors. Modification analyses were performed to identify whether 25 (OH)D altered the above associations. Results. A 1 SD increase in cortisol was associated with a higher prevalence of stroke (odds ratio (OR): 1.25, 95% confidence interval (CI): 1.05, 1.50). Elevated cortisol was associated with related cardiovascular risk factors, including deceased ß cell function, high-density lipoprotein-cholesterol (HDL-C), and fasting insulin, as well as increased triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c). In addition, modification analyses suggested that the associations of cortisol with ß cell function, fasting insulin, FPG, and HbA1c were modified by 25 (OH)D. Conclusions. Serum cortisol was associated with the prevalence of stroke and cardiovascular risk factors, and the associations of cortisol with cardiovascular risk factors were moderated by 25 (OH)D, suggesting that T2DM patients with exposure to lower 25 (OH)D levels and higher cortisol levels were more susceptible to have higher cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

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]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Objective. The aim of the study was to investigate the independent and combined effects of the cortisol-to-cortisone ratio (F/E) and 11-deoxycortisol on prediabetes and type 2 diabetes mellitus (T2DM) among different genders. Methods. A case-control study was performed including 2676 participants from the Henan Rural Cohort Study. Liquid chromatography-tandem mass spectrometry was used to assess serum cortisol, cortisone, and 11-deoxycortisol. Conditional logistic regression was performed to estimate the associations between hormones and outcomes. Results. After adjusting for multiple variables, the negative associations of F/E and 11-dexyocortisol with T2DM were observed in females (T3 vs. T1: OR=0.56, 95% CI: 0.39-0.80 for F/E; T3 vs. T1: OR=0.44, 95% CI: 0.27-0.73 for 11-dexyocortisol). However, only 11-dexyocortisol showed a negative association with prediabetes both in males and females. Compared with the combination of low F/E and 11-dexyocortisol, the combination of middle F/E and high 11-dexyocortisol was significantly associated with prediabetes (OR=0.29, 95% CI: 0.12-0.71) in males. Furthermore, the combination of high F/E and 11-dexyocortisol was associated with the lowest odds of prediabetes (OR=0.39, 95% CI: 0.21-0.73) and T2DM (OR=0.25, 95% CI: 0.12-0.52) in females. Conclusions. Serum F/E level was negatively associated with T2DM only in females whereas serum 11-deoxycortisol level was negatively associated with prediabetes in males and with prediabetes and T2DM in females. Additionally, their combination has a synergistic effect on 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]

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]

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]

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]

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]