The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2′-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2′-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder.

Studies have found that ambient particulate matter (PM) affects fasting blood glucose. However, the results are not consistent. We conducted a systematic review and meta-analysis to determine the relationship between PM with an aerodynamic diameter of 10 μm or less (PM₁₀) and PM with an aerodynamic diameter of 2.5 μm or less (PM₂.₅) and fasting blood glucose. We searched PubMed, Web of Science, the Wanfang Database and the China National Knowledge Infrastructure up to April 1, 2019. A total of 24 papers were included in the review, and 17 studies with complete or convertible quantitative information were included in the meta-analysis. The studies were divided into groups by PM size fractions (PM₁₀ and PM₂.₅) and length of exposure. Long-term exposures were based on annual average concentrations, and short-term exposures were those lasting less than 28 days. In the long-term exposure group, fasting blood glucose increased 0.10 mmol/L (95% CI: 0.02, 0.17) per 10 μg/m³ of increased PM₁₀ and 0.23 mmol/L (95% CI: 0.01, 0.45) per 10 μg/m³ of increased PM₂.₅. In the short-term exposure group, fasting blood glucose increased 0.02 mmol/L (95% CI: −0.01, 0.04) per 10 μg/m³ of increased PM₁₀ and 0.08 mmol/L (95% CI: 0.04, 0.11) per 10 μg/m³ of increased PM₂.₅. Further prospective studies are needed to explore the relationship between ambient PM exposure and fasting blood glucose.

Associations between single metal and fasting blood glucose (FBG) levels have been reported in previous studies. However, the association between multi-metals exposure and FBG level are little known. To assess the joints of arsenic (As), nickel (Ni), cadmium (Cd), selenium (Se), and zinc (Zn) co-exposure on FBG levels, Bayesian kernel machine regression (BKMR) statistical method was used to estimate the potential joint associations between As, Ni, Cd, Se, and Zn co-exposure and FBG levels among 1478 community-based Chinese adults from two counties, Shimen (n = 696) and Huayuan (n = 782), with different exposure profiles in Hunan province of China. The metals levels were measured in spot urine (As, Ni, and Cd) and plasma (Se and Zn) using inductively coupled plasma-mass spectrometry, respectively. The exposure levels of all the five metals were significantly higher in Shimen area (median: As = 57.76 μg/L, Cd = 2.75 μg/L, Ni = 2.73 μg/L, Se = 112.67 μg/L, Zn = 905.68 μg/L) than those in Huayuan area (As = 41.14 μg/L, Cd = 2.22 μg/L, Ni = 1.88 μg/L, Se = 65.59 μg/L, Zn = 819.18 μg/L). The BKMR analyses showed a significantly positive over-all effect of the five metals on FBG levels when metals concentrations were all above the 50th percentile while a statistically negative over-all effect when metals concentrations were all under the 50th percentile in Shimen area. However, a totally opposite over-all effect of the mixture of the five metals on FBG levels was found in Huayuan area. BKMR also revealed a non-linear exposure-effect of Zn on FBG levels in Huayuan area. In addition, interaction effects of As and Se on FBG level were observed. The relationship between single or combined metals exposure and FBG was different against different exposure profiles. Potential interaction effects of As and Se on FBG levels may exist.

Carbon disulfide (CS₂) has been reported to induce disorder of glucose metabolism. However, the associations of CS₂ exposure with plasma glucose levels and risk of diabetes have not been explored in general population, and the underlying mechanisms remain unclear. We aim to examine the relationships between CS₂ exposure and fasting plasma glucose (FPG) levels, as well as diabetes, and assess the potential role of oxidative stress among the abovementioned relationships in Chinese general adults. The concentrations of urinary biomarkers of CS₂ exposure (2-thiothiazolidin-4-carboxylic acid, TTCA), and biomarkers for lipid peroxidation (8-isoprostane, 8-iso-PGF₂α) and DNA oxidative damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) were measured among 3338 urban adults from the Wuhan-Zhuhai cohort. Additionally, FPG levels were tested promptly. Generalized linear models and logistic regression models were used to quantify the associations among urinary TTCA, oxidative damage markers, FPG levels and diabetes risk. Mediation analysis was employed to estimate the role of oxidative damage markers in the association between urinary TTCA and FPG levels. We discovered a significant relationship between urinary TTCA and FPG levels with regression coefficient of 0.080 (95% CI: 0.002,0.157). Besides, the risk of diabetes was positively related to urinary TTCA (OR:1.282, 95% CI: 1.055,1.558), particularly among those who did not exercise regularly. Each 1% increase of urinary TTCA concentration was associated with a 0.096% and 0.037% increase in urinary 8-iso-PGF₂α and 8-OHdG, respectively. Moreover, we found an upward trend of FPG level as urinary 8-iso-PGF₂α gradually increased (Pₜᵣₑₙd<0.05), and urinary 8-iso-PGF₂α mediated 21.12% of the urinary TTCA-associated FPG increment. Our findings indicated that urinary CS₂ metabolite was associated with increased FPG levels and diabetes risk in general population. Lipid peroxidation partly mediated the association of urinary CS₂ metabolite with FPG levels.

As a common health indicator in physical examinations, fasting blood glucose (FBG) level measurements are widely applied as a diagnostic method for diabetes mellitus. Uncertain conclusions remained regarding the relationship between PM₂.₅ exposure and FBG levels. We enrolled 47,471 subjects who participated in annual physical examinations between 2017 and 2019. We collected their general characteristics and FBG levels, and environmental factors simultaneously. We applied the generalized additive model to evaluate the impact of short-term outdoor PM₂.₅ exposure on FBG levels. Among the entire population, the single-pollutant models showed that a 10 μg/m³ increase in PM₂.₅ significantly contributed to 0.0030, 0.0233, and 0.0325 mmol/L increases in FBG at lag 0–7 days, lag 0–21 days, and lag 0–28 days, respectively. Accordingly, in multipollutant models, when PM₂.₅ increased by 10 μg/m³, there was an elevation of 0.0361, 0.0315, 0.0357, and 0.0387 mmol/L in FBG for 8-day, 15-day, 22-day, and 29-day moving averages, respectively. Similarly, we observed a significant positive association between them in the normal population. Moreover, the effects could be modified by age in both the entire and normal populations. Decreasing the ambient PM₂.₅ concentrations can alleviate the elevation of FBG, which may significantly impact the burden of diabetes mellitus.

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been widely studied for their mutagenic and carcinogenic effects. This study aims to investigate whether exposure to nitro-PAHs is associated with biomarkers of carbohydrate metabolism, an underlying risk factor for metabolic disorder. Early morning urine and blood samples were longitudinally collected two times with a four-week interval from 43 healthy adults. Five urinary amino-PAHs (1-aminonaphthalene, 2-aminonaphthalene, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene) were measured as biomarkers of nitro-PAH exposures. We measured plasma concentrations of glucose and six amino acids that can regulate insulin secretion, including aspartate (Asp), glutamate (Glu), glutamine (Gln), alanine (Ala), Arginine (Arg), and ornithine (Orn). We found that increasing concentrations of 9-aminophenanthrene were significantly associated with increasing glucose levels and with decreasing Asp, Glu, Ala, and Orn levels. We estimated that 26.4 %–43.8 % of the 9-aminophenanthrene-associated increase in glucose level was mediated by Asp, Glu, and Orn. These results suggest that exposure to certain nitro-PAHs affects glucose homeostasis, partly resulting from the depletion of insulin-stimulating amino acids (Asp, Glu, and Orn).

Previous studies have reported metals exposure contribute to the change of fasting blood glucose (FBG) level. However, the roles of reproductive hormones in their associations have not been fully elucidated. The aim of the study is to investigate the associations of multiple serum metals with reproductive hormones, and to further explore potential roles of reproductive hormones in relationships between metals exposure and FBG level. A total of 1911 Chinese Han men were analyzed by a cross-sectional study. We measured serum levels of 22 metals by inductively coupled plasma mass spectrometer (ICP-MS). FBG, total testosterone (TT), estradiol (E2), follicle stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels were determined. Least absolute shrinkage and selection operator (LASSO) regression models were conducted to select important metals, and restricted cubic spline models were then used to estimate dose-response relationships between selected metals and reproductive hormones. We also conducted mediation analyses to evaluate whether reproductive hormones played mediating roles in the associations between metals and FBG. We found significant inverse dose-dependent trends of copper, tin and zinc with E2; zinc with SHBG; copper and nickel with TT, while significant positive dose-dependent trend of iron with E2, respectively. Moreover, approximately inverted U-shaped associations existed between lead and SHBG, iron and TT. In addition, E2, SHBG and TT were negatively associated with FBG level. In mediation analyses, the association of copper with FBG was mediated by E2 and TT, with a mediation ratio of 10.4% and 22.1%, respectively. Furthermore, E2 and SHBG mediated the relationship of zinc with FBG, with a mediation ratio of 7.8% and 14.5%, respectively. E2 mediated 11.5% of positive relationship between tin with FBG. Our study suggested that the associations of metals exposure with FBG may be mediated by reproductive hormones.

Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Pregnant C57BL6/J mice were exposed to BPS (1.5 μg/kg bw/day ie a human equivalent dose of 0.12 μg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.

Exposure to endocrine disrupting chemicals during the first 1000 days of life may have long-lasting adverse effects on cardio-metabolic risk in later life. This study aimed to examine the associations between maternal prenatal Bisphenol A (BPA) exposure and child cardio-metabolic risk factors at age 2 years in a prospective cohort. During 2012–2013, 218 pregnant women were enrolled at late pregnancy from Shanghai, China. Urinary BPA concentration was measured in prenatal and child 2-year spot urine samples, and classified into high, medium and low tertiles. Child adiposity anthropometric measurements, random morning plasma glucose, serum insulin, and lipids (high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride), systolic (SBP) and diastolic blood pressure (DBP) were measured. Linear regression was used to evaluate the associations between prenatal BPA and each of the cardio-metabolic risk factors in boys and girls, respectively, adjusting for pertinent prenatal, perinatal and postnatal factors. BPA was detectable (>0.1 μg/L) in 98.2% of mothers prenatally and 99.4% of children at age 2 years. Compared to those with low prenatal BPA, mean SBP was 7.0 (95%CI: 2.9–11.2) mmHg higher, and DBP was 4.4 (95%CI: 1.2–7.5) mmHg higher in girls with high prenatal BPA levels, but these associations were not found in boys. In boys, medium maternal prenatal BPA level was associated with 0.36 (95% CI: 0.04–0.68) mmol/L higher plasma glucose. No associations were found between prenatal BPA and child BMI, skinfold thicknesses, serum lipids, or insulin in either girls or boys. There were no associations between concurrent child urinary BPA and cardio-metabolic risk factors. These results support that BPA exposure during prenatal period, susceptible time for fetal development, may be associated with increase in child BP and plasma glucose in a sex-specific manner. Further independent cohort studies are needed to confirm the findings.

A limited but emerging body of evidence is suggestive for a beneficial association between contact with green spaces and glucose homeostasis in adults; however, such an evidence for children is scarce. We evaluated the association between time spent in green spaces and fasting blood glucose (FBG) levels and impaired fasting glucose (IFG, FBG≥110 mg/dL) in a population-based multicentric sample of 3844 Iranian schoolchildren aged 7–18 years (2015). Participants were instructed to report the average hours per week spent in green spaces separately during each season and in each type of green space (parks, woods/other natural green spaces, and private gardens/agricultural field) for a 12-month period preceding the interview. We developed linear and logistic mixed effects models with centre as random effect to evaluate the association of time spent in green spaces (separately for each type as well as all types together) with FBG and IFG, respectively, controlled for a wide range of covariates including household indicators of socioeconomic status. We observed inverse associations between time spent in green spaces, especially in natural green spaces, and FBG levels. Specifically, 1.83 h increase in the total time spent in green spaces was associated with −0.5 mg/dl (95% confidence intervals: −0.9, −0.1) change in FBG levels. We also observed reduced risk of IFG associated with time spent in green spaces; however, the association was statistically significant only for the time spent in natural green spaces. There were suggestions for stronger associations for those residing in urban areas and those from lower socioeconomic status groups; however, the interaction terms for socioeconomic status and urbanity were not statistically significant. Further longitudinal studies are required to replicate our findings in other settings with different climates and population susceptibilities.