Effects of hepatitis B virus infection, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase on prediabetes and diabetes mellitus: A cohort study.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to confirm whether hepatitis B virus (HBV) infection and the levels of liver enzymes would increase the risk of prediabetes and diabetes mellitus (DM) in China. MATERIALS AND METHODS: A total of 10,741 individuals was enrolled in this prospective cohort study. Cox regression analysis was used to calculate the Hazard ratios (HRs) to evaluate the relationships between HBV infection and the risk of DM and prediabetes. Decision trees and dose response analysis were used to explore the effects of liver enzymes levels on DM and prediabetes. RESULTS: In baseline population, HBV infection ratio was 5.31%. In non-adjustment model, the HR of DM in HBV infection group was 1.312 (95% CI, 0.529-3.254). In model adjusted for gender, age and liver cirrhosis, the HR of DM in HBV infection group were 1.188 (95% CI, 0.478-2.951). In model adjusted for gender, age, liver cirrhosis, smoking, drinking, the HR of DM was 1.178 (95% CI, 0.473-2.934). In model further adjusted for education, family income and occupation, the HR of DM was 1.230 (95% CI, 0.493-3.067). With the increases of levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma-glutamyl transferase (GGT), the risk of prediabetes was gradually increasing (Pnon-linearity<0.05). There were dose-response relationships between ALT, GGT and the risk of DM (Pnon-linearity<0.05). CONCLUSIONS: HBV infection was not associated with the risk of prediabetes and DM. The levels of liver enzymes increased the risk of prediabetes and DM.

Liver Enzymes, Fatty Liver and Type 2 Diabetes Mellitus in a Jinchang Cohort: A Prospective Study in Adults.

OBJECTIVES: It is unclear whether liver enzymes or the interactions of various liver enzymes is a predictor of type 2 diabetes mellitus (T2DM), which is independent of fatty liver. METHODS: A total of 48,001 subjects participated in baseline examinations. Among the subjects, 33,355 were followed for an average of 2.2 years. Cox proportional hazard models were used to examine the adjusted associations of AST, GGT and ALT with T2DM. RESULTS: The cumulative incidence of T2DM was 8.05% to 9.02% for fatty liver and 2.25% to 4.10% for non-fatty liver, both showing statistically significant differences. Compared with the normal liver enzyme levels in the group with fatty liver, the adjusted incident hazard ratios in T2DM were: ALT 1.23 (95% CI 1.10 to 1.50); AST 1.30 (95% CI 1.07-1.59); and GGT 1.34 (95% CI 1.08 to 1.65). In addition, compared with the normal liver enzyme levels in the group with non-fatty liver, the adjusted incident hazard ratios in type 2 diabetes were: ALT 1.27 (95% CI 1.02 to 1.59); AST 1.33 (95% CI 1.02 to 1.59); and GGT 1.53 (95% CI 1.19 to 1.98). There are significant interactions of T2DM hazard ratios between GGT and ALT and between GGT and AST in addition to ALT and AST. CONCLUSIONS: Our results suggest that the incidence of T2DM in the group with fatty liver is significantly higher than that in the normal population, and the rise of serum AST, GGT and ALT levels are risk factors independent of fatty liver for the development of T2DM after adjusting for confounding factors.

Dose-response analysis of environmental exposure to multiple metals and their joint effects with fasting plasma glucose among occupational workers.

OBJECTIVES: Environmental exposure to metals may adversely affect cardiometabolic health. However, little data are available directly evaluating the roles of metal exposure in blood glucose of which dysfunction has been linked to diabetes. We aimed to evaluate the dose-response associations between fasting plasma glucose (FPG) and multiple urinary metals including nickel, cobalt, copper, zinc, and arsenic, as well as to examine their joint effects among occupational workers. METHODS: We performed a population-based study of 464 workers in an ongoing occupational cohort study in China. Both spline and categorical analyses were used to evaluate the dose-response relationship between urinary metals levels and FPG. RESULTS: We observed the J-shaped non-linear relationships between urinary nickel (P non-linearity = 0.03) and zinc (P non-linearity < 0.01) with FPG by spline analyses. A negative linear relationship between urinary cobalt and FPG (P for nonlinearity = 0.06) was found, but no statistically significant associations between urinary copper and arsenic with FPG. In linear regression analyses, the regression coefficient for log-transferred FPG was 0.017 (95% confidence intervals [CI]: -0.003, 0.038) in the 4th quartile concentration of urinary nickel, compared with 1st quartile. The joint effects between urinary nickel and cobalt with FPG were also detected (P for interaction = 0.04). CONCLUSIONS: Multiple urinary metals, particularly nickel, zinc and cobalt, were associated with blood glucose among Chinese metal exposed workers, supporting the notion that metal exposure may play a critical role in diabetes development.

Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers.

OBJECTIVE: To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers. METHODS: Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels. RESULTS: H3K4me3 was statistically significantly different (p < 0.05) between the two groups and positively correlated with employment length (rs = 0.267). HP1 was not correlated with employment length (p = 0.066) but was significantly different between the two groups. CONCLUSIONS: Chronic exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.

Multiple metals exposure, elevated blood glucose and dysglycemia among Chinese occupational workers.

AIMS: Exposure to metals may adversely affect cardiometabolic health. The aim of this study is to directly evaluate the roles of multiple metals exposure in glucose homeostasis, the dysfunction of which has been linked to diabetes and cardiovascular diseases (CVDs). METHODS: We performed a cross-sectional analysis of baseline data from 464 metal-exposed workers who participated in a large prospective occupational study in China (Jinchang Cohort). The logistic regression model was used to evaluate the association between urinary metal levels and high fasting plasma glucose (high-FPG) (≥ 75th percentile) and dysglycemia. RESULTS: Increasing levels of urinary nickel were prospectively associated with high-FPG: multivariable odds ratios (ORs) were 1.00 for the 1st quartile (lowest), 1.20 (95% confidence interval [CI]: 0.60-2.43) for the 2nd quartile, 1.64 (0.78-3.49) for the 3rd quartile and 3.17 (1.38-7.30) for the 4th quartile (highest) (P-trend=0.004). The positive associations were also observed between urinary zinc and high-FPG (4th vs. 1st quartile=2.71, 95%CI: 1.26-5.84, P-trend=0.01). Inverse associations between urinary cobalt and risk of high-FPG and dysglycemia were observed (P-trend <0.05). For dysglycemia, the positive trends of increasing levels of urinary nickel and zinc still remained, although urinary nickel was no longer statistically significant. A significant association between urinary arsenic and dysglycemia was also found. However, no associations were observed between urinary copper, cadmium, and risk of high-FPG or dysglycemia. CONCLUSION: Multiple urinary metals, particularly arsenic, nickel, zinc, and cobalt, were associated with elevated blood glucose among Chinese occupational workers, supporting the notion that metal exposure plays a critical role in the development of diabetes.

Reproductive factors and risk of type 2 diabetes in an occupational cohort of Chinese women.

AIMS: Hormonal milieu has long been known to play an important role in the development of type 2 diabetes (T2D). The aims of this study are to investigate the roles of menstrual and reproductive factors in relation to T2D risk in an occupational cohort of Chinese women; and to explore the role of endogenous estrogen in T2D development. METHODS: We conducted a cross-sectional analysis of baseline data from 16114 women (11051 premenopausal and 5063 postmenopausal) aged ≥20years who participated in the ongoing prospective occupational cohort study. Multivariable logistic regressions were modeled to evaluate the associations of reproductive factors with T2D risk. RESULTS: Early menarche at age (≤12 versus 15-16 years) was associated with increased T2D risk (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.16-2.22). After multiple adjustment including age, BMI and occupation, postmenopausal status was positively associated with T2D risk (OR: 1.54, 95% CI: 1.10-2.14). Reproductive life span was significantly associated with T2D risk (P=0.02), albeit displaying a U-shape relationship. Similarly, age at menopause was also associated with T2D risk in the same U-shaped as with reproductive life span (P=0.03). Further, years since menopause (P=0.003), but not history of cycle regularity and hormone use, was associated with increased T2D risk. CONCLUSION: Reproductive factors were associated with T2D supporting the notion that either a short or prolonged exposure to endogenous estrogen affects T2D risk in Chinese women. Reproductive factors should be added to risk stratification when counseling women about their risk of developing diabetes.

[Application of cohort study in cancer prevention and control].

Cancer control is a long-term work. Cancer research and intervention really need the support of cohort study. In the recent years, more and more cohort studies on cancer control were conducted in China along with the increased ability of scientific research in China. Since 2010, Cancer Hospital, Chinese Academy of Medical Sciences, collaborated with Lanzhou University and the Worker' s Hospital of Jinchuan Group Company Limited, have carried out a large-scale cohort study on cancer, which covered a population of more than 50 000 called " Jinchang cohort". Since 2012, a National Key Public Health Project, "cancer screening in urban China" , has been conducted in Jinchang, which strengthened the Jinchang cohort study. Based on the Jinchang cohort study, historical cohort study, cross-sectional study and prospective cohort study have been conducted, which would provide a lot of evidence for the cancer control in China.

[Cancer burden in the Jinchang cohort].

OBJECTIVE: To understand the disease burden caused by cancers in Jinchang cohort, and develop effective strategies for cancer prevention and control in this population. METHODS: The cancer mortality data from 2001 to 2013 and the medical records for cancer patients from 2001 to 2010 in Jinchang cohort were collected. The disease burden caused by cancer was analyzed by using mortality rate, potential years of life lost (PYLL), working PYLL (WPYLL), and direct economic burden. RESULTS: During 2001-2013, in Jinchang cohort, the five leading cancers ranked by mortality rate were lung cancer (78.06/100,000), gastric cancer (38.03/100,000), liver cancer (37.23/100,000), esophageal cancer (19.06/100,000), and colorectal cancer (9.53/100,000). The five leading cancers in terms of PYLL (person-years) and WPYLL (person-years) were lung cancer (3480.33, 1161.00), liver cancer (2809.03, 1475.00), gastric cancer (2120.54, 844.00), esophageal cancer (949.61, 315.00), and colorectal cancer (539.90, 246.00). From 2001 to 2010, the five leading cancers in term of average daily cost of hospitalization were gastric cancer (8,102.23 Yuan), esophageal cancer (7135.79 Yuan), colorectal cancer (7064.38 Yuan), breast cancer (6723.53 Yuan), and lung cancer (6309.39 Yuan). CONCLUSIONS: The cancers common causing higher disease burden in Jinchang cohort were lung cancer, gastric cancer, liver cancer, esophageal cancer and colorectal cancer. The lung cancer disease burden was the highest.

[Disease burden of lung cancer in Jinchang cohort].

OBJECTIVE: To understand the current status of lung cancer disease burden in Jinchang cohort. METHODS: In this historical cohort study, the mortality data of the lung cancer from 2001 to 2013 and medical records of the lung cancer cases from 2001 to 2010 in Jinchang cohort were used, analyze mortality, direct economic burden, potential years of life lost (PYLL) and working PYLL (WPYLL) associated with lung cancer. RESULTS: A total of 434 lung cancer deaths occurred in Jinchang cohort from 2001 to 2013. The crude mortality rate of lung cancer was 78.06 per 100,000 from 2001 to 2013, with the increasing rate of 4.77%. The mortality rate of lung cancer in males and females were about 108.90 per 100,000 and 26.08 per 100,000 with the increasing rate of 4.24% and 6.91%, respectively. During the thirteen years, the PYLL and average PYLL (APYLL) of lung cancer were 3 721.71 person-years and 8.58 years. The APYLL of lung cancer in females (15.94 years) was higher than that in males (7.87 years). The WPYLL and the average WPYLL (AWPYLL) of lung cancer were 1161.00 person-years and 2.68 years, respectively. The AWPYLL of lung cancer was also higher in females than in males. The direct economic burden of lung cancer from 2001 to 2010 in Jinchang cohort was 6309.39 Yuan per case with no increased trend. CONCLUSION: Lung cancer is the main health problem in Jinchang cohort, causing heavy disease burden.

[Disease burden of gastric cancer in Jinchang cohort].

OBJECTIVE: To understand the current status of disease burden caused by gastric cancer in Jinchang cohort. METHODS: In this historical cohort study, the data of gastric cancer deaths from 2001 to 2013 and the medical records of gastric cancer cases from 2001 to 2010 in Jinchang cohort were collected to analyze the mortality, potential years of life lost (PYLL), working PYLL (WPYLL) associated with gastric cancer, and the medical expenditure data were used to evaluate the direct economic burden. Spearman correlation analysis and the average growth rate were used to describe the change trend of disease burden of gastric cancer. RESULTS: A total of 213 gastric cancer deaths occurred in Jinchang cohort from 2001 to 2013. The average annual crude mortality rate of gastric cancer was 38.30 per 100,000 in Jinchang cohort during 2001-2013 and no obvious change was observed. The crude mortality rate in males was 6.84 times higher than that in females. Gastric cancer death mainly occurred in age group 50-79 years (82.62%), while the mortality rates was increasing among the people under 50 years with an average annual increase rate of 0.77%. The annual average PYLL (APYLL) and average WPYLL (AWPYLL) caused by gastric cancer decreased by 8.43% and 10.46%, respectively. No obvious change in medical expenditure of gastric cancer cases was observed in Jinchang Cohort during 2001-2010, and the medical expenditure and average daily cost of hospitalization were 8102.23 Yuan, and 463.45 Yuan per capita, respectively. CONCLUSIONS: The burden of disease for gastric cancer was heavy in Jinchang cohort. The PYLL and WPYLL had no change, while the APYLL and AWPYLL showed a increasing trend during the last ten years. Direct economic burden of inpatients with gastric cancer had no change.

[Disease burden of liver cancer in Jinchang cohort].

OBJECTIVE: To understand the current status of the disease burden of liver cancer in Jinchang cohort. METHODS: All the liver cancer death data from 2001 to 2013 and medical records of liver cancer cases from 2001 to 2010 in Jinchang cohort were collected for the analyses of the mortality, standardized mortality, potential years of life lost (PYLL) and working PYLL (WPYLL) associated with liver cancer. Spearman correlation and the average growth rate were used to analyze the trends. RESULTS: A total of 207 liver cancer deaths occurred in Jinchang cohort from 2001 to 2013, accounting for 16.68% of total cancer deaths. There were 259 liver cancer inpatients, accounting for 6.79% of the total cancer cases inpatients, in which 83 died (32.05%). Liver cancer death mainly occurred in males, accounting for 88.89%, and the liver cancer deaths in females accounted for 11.11%. The standardized mortality rate was 42.32/100,000 in males and 15.31/100,000 in females. The growth rate of liver cancer mortality was 5.62% from 2001 to 2013. Liver cancer deaths mainly occurred in age groups 60-69 years (26.57%) and 50-59 years (24.15%). The PYLL was 2906.76 person-years, the average PYLL was 14.04 years. The WPYLL was 1477.00 person-years and the average WPYLL was 7.14 years. The direct economic burden of liver cancer was 6270.78 Yuan per person, 301.75 Yuan per day. The average stay of hospitalization was 21.32 days. CONCLUSION: The mortality rate of liver cancer is increasing and the disease burden is still heavy.

[Disease burden of colorectal cancer in Jinchang cohort].

OBJECTIVE: To evaluate the disease burden of colorectal cancer in Jinchang cohort, and provide evidence for preventing colorectal cancer and reducing the disease burden of colorectal cancer in the cohort. METHODS: The colorectal cancer mortality data from 2001 to 2013 and the medical records of colorectal cancer patients from 2001 to 2010 were collected for this retrospective cohort study. The colorectal cancer disease burden was described by using mortality rate, standardized mortality rate, medical expenditure, potential years of life lost (PYLL), average potential years of life lost (APYLL), working potential years of life lost (WPYLL), and average working potential years of life lost (AWPYLL). The development trend in disease burden of colorectal cancer was analyzed by using Spearman correlation and the average growth rate. RESULTS: The crude mortality rate of colorectal cancer from 2001 to 2013 was 9.53/100,000 with the average annual growth rate of 12.89%. The PYLL, APYLL, WPYLL and AWPYLL of colorectal cancer were 485.00 person-years, 9.15 years, 253.00 person-years, and 4.77 years, respectively. The direct medical expenditure due to colorectal cancer was 7064.38 Yuan per case and 408.43 Yuan per day. There was no increasing trend in the direct medical expenditure due to colorectal cancer. CONCLUSION: Colorectal cancer mortolity rate was on the rise and it caused heavy disease burden in Jinchang cohort.

Histone Methylation in Nickel-Smelting Industrial Workers.

BACKGROUND: Nickel is an essential trace metal naturally found in the environment. It is also common in occupational settings, where it associates with various levels of both occupational and nonoccupational exposure In vitro studies have shown that nickel exposure can lead to intracellular accumulation of Ni2+, which has been associated with global decreases in DNA methylation, increases in chromatin condensation, reductions in H3K9me2, and elevated levels of H3K4me3. Histone modifications play an important role in modulating chromatin structure and gene expression. For example, tri-methylation of histone H3k4 has been found to be associated with transcriptional activation, and tri-methylation of H3k27 has been found to be associated with transcriptional repression. Aberrant histone modifications have been found to be associated with various human diseases, including cancer. The purpose of this work was to identify biomarkers for populations with occupational nickel exposure and to examine the relationship between histone methylation and nickel exposure. This may provide a scientific indicator of early health impairment and facilitate exploration of the molecular mechanism underlying cancer pathogenesis. METHODS: One hundred and forty subjects with occupational exposure to Ni and 140 referents were recruited. H3K4 and H3K27 trimethylation levels were measured in subjects' blood cells. RESULTS: H3K4me3 levels were found to be higher in nickel smelting workers (47.24±20.85) than in office workers (22.65±8.81; P = 0.000), while the opposite was found for levels of H3K27me3(nickel smelting workers, 13.88± 4.23; office workers, 20.67± 5.96; P = 0.000). H3K4me3 was positively (r = 0.267, P = 0.001) and H3K27 was negatively (r = -0.684, P = 0.000) associated with age and length of service in smelting workers. CONCLUSION: This study indicated that occupational exposure to Ni is associated with alterations in levels of histone modification.

[Observation on both Na(+)-K+ Atpase activity and expression of Na(+)-K+ AtPase alpha1 mRNA in lung tissues of rats acute poisoned with nickel carbonyl].

OBJECTIVE: To examine the change of Na(+)-K+ ATPase activity and the expressions of Na(+)-K+ ATPase alpha1 mRNA in lung tissues of rats poisoned by nickel carbonyl and to discuss the mechanism of lung injury. METHODS: One hundred seventy healthy rats (85 male and 85 female) were exposed by inhalation of 20,135 and 250 mg/m3 nickel carbonyl for 30 min. Rats poisoned by chlorine gas with a concentration 250 mg/m3 served as positive group and healthy SD rats served as no-treatment negative group. The rats were euthanized on 1, 2, 3 and 7 d after the administration of nickel carbonyl or chlorine gas. In various treatment groups, Na(+)-K+ ATPase activity was studied by colorimetric method and the expressions of Na(+)-K+ ATPase alpha1 mRNA were determined by RT-PCR. RESULTS: Na(+)-K+ ATPase activity and expressions of Na(+)-K+ ATPase alpha1 mRNA in lung tissues decreased in all treatment groups and chlorine gas-poisoned group, especially it was obvious decreased on the 2ed and 3rd day (P < 0.05). CONCLUSION: Nickel carbonyl could induce lung damage and decrease Na(+)-K+ ATPase activity and expressions of Na(+)-K+ ATPase alpha1 mRNA in lung.