Associations between Plasma Essential Metals Levels and the Risks of All-Cause Mortality and Cardiovascular Disease Mortality among Individuals with Type 2 Diabetes.

Epidemiological evidence regarding the possible link between multiple essential metals levels and all-cause mortality and cardiovascular disease (CVD) mortality among type 2 diabetes (T2D) patients is sparse. Here, we aimed to evaluate the longitudinal associations between 11 essential metals levels in plasma and all-cause mortality and CVD mortality among T2D patients. Our study included 5278 T2D patients from the Dongfeng-Tongji cohort. LASSO penalized regression analysis was used to select the all-cause and CVD mortality-associated metals from 11 essential metals (iron, copper, zinc, selenium, manganese, molybdenum, vanadium, cobalt, chromium, nickel, and tin) measured in plasma. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With a median follow-up of 9.8 years, 890 deaths were documented, including 312 deaths of CVD. LASSO regression models and the multiple-metals model revealed that plasma iron and selenium were negatively associated with all-cause mortality (HR: 0.83; 95%CI: 0.70, 0.98; HR: 0.60; 95%CI: 0.46, 0.77), whereas copper was positively associated with all-cause mortality (HR: 1.60; 95%CI: 1.30, 1.97). Only plasma iron has been significantly associated with decreased risk of CVD mortality (HR: 0.61; 95%CI: 0.49, 0.78). The dose-response curves for the association between copper levels and all-cause mortality followed a J shape (Pfor nonlinear = 0.01). Our study highlights the close relationships between essential metals elements (iron, selenium, and copper) and all-cause and CVD mortality among diabetic patients.

NRF2 Genetic Polymorphism Modifies the Association of Plasma Selenium Levels With Incident Coronary Heart Disease Among Individuals With Type 2 Diabetes.

Plasma selenium and NRF2 promoter variants (e.g., rs6721961) are associated with cardiovascular disease risk in the general population. However, epidemiological evidence on the interaction between plasma selenium and NRF2 genetic susceptibility in relation to incident coronary heart disease (CHD) risk remains scarce, especially among individuals with type 2 diabetes (T2D). Thus, we examined whether rs6721961 in the NRF2 gene might modify the association between plasma selenium levels and incident CHD risk among people with T2D. During a mean (SD) follow-up period of 6.90 (2.96) years, 798 incident CHD cases were identified among 2,251 T2D cases. Risk-allele carriers of rs6721961 had a higher risk of incident CHD among people with T2D (adjusted hazard ratio [HR] 1.17; 95% CI 1.02-1.35) versus nonrisk-allele carriers. Each 22.8-µg/L increase in plasma selenium levels was associated with a reduced risk of incident CHD among risk-allele carriers with T2D (HR 0.80; 95% CI 0.71-0.89), whereas no association was found in those without risk alleles (P for interaction = 0.004), indicating that the NRF2 promoter polymorphism might modify the association between plasma selenium levels and incident CHD risk among people with T2D. Our study findings suggest redox-related genetic variants should be considered to identify populations that might benefit most from selenium supplementation. More mechanistic studies are warranted.

Plasma metal concentrations and their interactions with genetic susceptibility on homocysteine levels.

Limited studies have evaluated the associations of multiple metal exposures with homocysteine (Hcy) levels, which were independent risk factor for cardiovascular disease (CVD). Furthermore, the interactions between genetic variants and plasma metals in relation to Hcy levels were largely unknown. We aimed to explore the associations of multiple plasma metals (including metalloids arsenic [As] and selenium [Se]) with Hcy levels and whether their associations were modified by genetic susceptibility. We included 2989 participants from the baseline of the Dongfeng-Tongji cohort (DFTJ cohort) and conducted a cross-sectional study to explore the associations of 17 plasma metals with serum Hcy levels. Both multi-variable linear regression model (single-metal model) and LASSO penalized regression model (multiple-metal model) were used to identify the Hcy-associated metals. The weighted genetic risk score (GRS) was calculated based on 18 established Hcy-associated genetic variants. For metals that were associated with Hcy, we further assessed the gene-metal interactions on Hcy levels. Among 17 metals, plasma molybdenum (Mo), strontium (Sr), and Zinc (Zn) were positively associated with Hcy levels, whereas Se was inversely associated with Hcy levels in both single- and multiple-metal models. We also observed that the genetic predisposition to Hcy significantly modified the association between plasma Se and serum Hcy levels (P for interaction = 0.003), while no significant gene-metal interactions were found for Mo, Sr, and Zn (all P for interactions > 0.05). These findings provide novel insight into the associations of the plasma concentrations of Mo, Se, Sr and Zn with Hcy levels and address the importance of Se as a potential upstream modifiable factor for the personalized prevention of elevated Hcy levels and CVD.

Plasma titanium level is positively associated with metabolic syndrome: A survey in China's heavy metal polluted regions.

OBJECTIVE: Several heavy metals have been reported to be associated with metabolic syndrome(MetS) in general population, while effects of multiple metals exposure on MetS in residents living in heavy metal polluted regions have not been investigated. We aimed to assess the association of 23 metal levels and MetS among population living in China's heavy metal polluted regions. METHODS: From August 2016 to July 2017, a total of 2109 eligible participants were consecutively enrolled in our study in Hunan province, China. The levels of plasma and urine metals were measured by inductively coupled plasma mass spectrometer (ICP-MS). MetS was defined by the criteria of the International Diabetes Federation. Multivariable regression models were applied to analysis the potential relationship. RESULTS: In the overall population, crude model showed positive relationship of plasma titanium (Ti) with MetS and negative association of urine vanadium, iron, and selenium with MetS. After adjusted for potential confounders, only plasma Ti was positive associated with MetS (adjusted OR for Q4 versus Q1: 1.46; 95% CI: 1.06-1.99), and this positive correlation was explained by abdominal obesity (OR = 1.84, 95% CI: 1.41-2.39) and high triglycerides (OR = 2.23, 95% CI: 1.68-2.96). Further linear regression analysis revealed significant association of plasma Ti levels with waist circumference (ß = 0.0056, 95% CI: 0.0004-0.0109, P = 0.036) and triglycerides (ß = 0.0012, 95% CI: 0.0006-0.0019, P < 0.001), respectively. CONCLUSION: High plasma Ti level was associated with increased risk of MetS via increasing waist circumference and triglycerides in people under high metal exposure.

Association between exposure to arsenic, nickel, cadmium, selenium, and zinc and fasting blood glucose levels.

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.

Green tea consumption is associated with reduced incident CHD and improved CHD-related biomarkers in the Dongfeng-Tongji cohort.

Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19,471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers.

Essential Metals Zinc, Selenium, and Strontium Protect against Chromosome Damage Caused by Polycyclic Aromatic Hydrocarbons Exposure.

Essential metals play important roles in maintaining cellular homeostasis, but the effects of their interaction with the environmental pollutants are still not very well-known in human subjects. The aim of this study was to evaluate the roles of essential metals and their interactions with polycyclic aromatic hydrocarbons (PAHs) on chromosome damage, an early carcinogenic event. A total of 1245 male workers were included in this study and the levels of 11 urinary essential metals, 12 urinary PAH metabolites, plasma concentrations of benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, and lymphocyte micronucleus (MN) frequencies were monitored. We found that zinc (Zn), selenium (Se), and strontium (Sr) have significant inverse dose-response relationships with MN frequencies (all P < 0.05). Furthermore, the protective roles of Zn, Se, and Sr were mainly shown among subjects with high levels of BPDE-Alb adducts. Significant effect modification of BPDE-Alb adducts on the associations of Zn, Se, and Sr with MN frequencies was observed (all Pinteraction < 0.05). Our study showed evidence that Zn, Se, and Sr play protective roles in reducing chromosome damage, and these effects can be modified by PAH exposure levels. These findings add potential evidence for the preventive effects of Zn, Se, and Sr against carcinogenesis in human subjects.

Different physical activity subtypes and risk of metabolic syndrome in middle-aged and older Chinese people.

BACKGROUND: The prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS. METHODOLOGY/PRINCIPAL FINDINGS: A total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66-0.86, P<0.001]. Compared with non-exercisers in a specific exercise type, jogging (OR 0.82, 95% CI 0.68-1.00, P = 0.046), tai chi (OR 0.72, 95% CI 0.60-0.88, P<0.001), and dancing (OR 0.56, 95% CI 0.47-0.67, P<0.001) were associated with significantly lower odds of MetS. Furthermore, each 1-h/week increment in tai chi and dancing was associated with a 5% (95% CI 2%-9%) and a 9% (95% CI 6%, 12%) lower risk of MetS. CONCLUSIONS/SIGNIFICANCE: Jogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS.