Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Effects of heart failure and coronary artery disease on erectile dysfunction: a two-sample mendelian randomization study.

BACKGROUND AND AIMS: There are no clear conclusions as to whether heart failure (HF) and coronary heart disease (CAD) increase the risk of erectile dysfunction (ED).In our study, we used Mendelian randomization (MR) analysis to discover a causal relationship between HF, CAD and ED. METHODS: Single nucleotide polymorphisms (SNPs) associated with HF, CAD and ED were obtained from the MRC IEU Open Genome-Wide Association Study (GWAS) database.After a series of screenings, the remaining SNPs were selected as instrumental variables (IVs) for HF and CAD for MR analysis to assess the relationship between genetically predicted HF or CAD and the pathogenesis of ED.Among them, we used the random-effects inverse variance weighted (IVW) method as the primary analysis method.Finally, Cochran's q-test, funnel plots, MR-Egger regression, Leave-one-out method and MR-PRESSO were used for sensitivity analysis. RESULTS: In the IVW method, there was no significant causal relationship between genetically predicted HF and CAD and the incidence of ED.(HF: OR = 1.17, 95% CI 0.99-1.39; p = 0.074;CAD: OR = 1.08, 95% CI 0.99-1.17, p = 0.068)。The results of sensitivity analyses supported our conclusion that no horizontal pleiotropism was found. CONCLUSION: This study did not find a causal relationship between HF or CAD and ED in European populations, which requires further in-depth research.

Mortality burden based on the associations of ambient PM2.5 with cause-specific mortality in China: Evidence from a death-spectrum wide association study (DWAS).

Although studies have estimated the associations of PM2.5 with total mortality or cardiopulmonary mortality, few have comprehensively examined cause-specific mortality risk and burden caused by ambient PM2.5. Thus, this study investigated the association of short-term exposure to PM2.5 with cause-specific mortality using a death-spectrum wide association study (DWAS). Individual information of 5,450,764 deaths during 2013-2018 were collected from six provinces in China. Daily PM2.5 concentration in the case and control days were estimated by a random forest model. A time-stratified case-crossover study design was applied to estimate the associations (access risk, ER) of PM2.5 with cause-specific mortality, which was then used to calculate the population-attributable fraction (PAF) of mortality and the corresponding mortality burden caused by PM2.5. Each 10 µg/m3 increase in PM2.5 concentration (lag03) was associated with a 0.80 % [95 % confidence interval (CI): 0.73 %, 0.86 %] rise in total mortality. We found greater mortality effect at PM2.5 concentrations < 50 µg/m3. Stratified analyses showed greater ERs in females (1.01 %, 95 %CI: 0.91 %, 1.11 %), children ≤ 5 years (2.17 %, 95 %CI: 0.85 %, 3.51 %), and old people ≥ 70 years. We identified 33 specific causes (level 2) of death which had significant associations with PM2.5, including 16 circulatory diseases, 9 respiratory diseases, and 8 other causes. The PAF estimated based on the overall association between PM2.5 and total mortality was 3.16 % (95 %CI: 2.89 %, 3.40 %). However, the PAF was reduced to 2.88 % (95 %CI: 1.88 %, 3.81 %) using the associations of PM2.5 with 33 level 2 causes of death, based on which 250.15 (95 %CI: 163.29, 330.93) thousand deaths were attributable to short-term PM2.5 exposure across China in 2019. Overall, this study provided a comprehensive picture on the death-spectrum wide association between PM2.5 and morality in China. We observed robust positive cause-specific associations of PM2.5 with mortality risk, which may provide more precise basis in assessing the mortality burden of air pollution.

Metabolomics study reveals systematic metabolic dysregulation and early detection markers associated with incident pancreatic cancer.

Biomarkers for early detection of pancreatic cancer are in urgent need. To explore systematic circulating metabolites unbalance and identify potential biomarkers for pancreatic cancer in prospective Chinese cohorts, we conducted an untargeted metabolomics study in subjects with incident pancreatic cancer and matched controls (n = 192) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We characterized 998 metabolites in baseline serum and calculated 156 product-to-precursor ratios based on the KEGG database. The identified metabolic profiling revealed systematic metabolic network disorders before pancreatic cancer diagnosis. Forty-Five metabolites or product-to-precursor ratios showed significant associations with pancreatic cancer (P < .05 and FDR < 0.1), revealing abnormal metabolism of amino acids (especially alanine, aspartate and glutamate), lipids (especially steroid hormones), vitamins, nucleotides and peptides. A novel metabolite panel containing aspartate/alanine (OR [95% CI]: 1.97 [1.31-2.94]), androstenediol monosulfate (0.69 [0.49-0.97]) and glycylvaline (1.68 [1.04-2.70]) was significantly associated with risk of pancreatic cancer. Area under the receiver operating characteristic curves (AUCs) was improved from 0.573 (reference model of CA 19-9) to 0.721. The novel metabolite panel was validated in an independent cohort with AUC improved from 0.529 to 0.661. These biomarkers may have a potential value in early detection of pancreatic cancer.

Interaction between smoking and diabetes in relation to subsequent risk of cardiovascular events.

BACKGROUND: Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. METHODS: This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011-2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. RESULTS: Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17-1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01-1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71-1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77-2.14) or former smokers (HR, 1.22; 95% CI, 0.66-2.28). CONCLUSIONS: Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.

Isotemporal substitution of different behaviour patterns with the presence of MAFLD in Chinese adults.

BACKGROUND: Lack of physical activity and excessive sitting time contributed to ectopic fat accumulation, especially in the liver. Previous studies have illustrated the harm of sedentary behaviour and the benefits of physical activity on fatty liver disease. We aimed to explore the association between the behaviour patterns and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) using isotemporal substitution model to examine the effect of replacing one behaviour to another while keeping the total time and other behaviours fixed among Chinese middle-aged and elderly population. METHODS: This study included 161 147 participants aged ≥40 years old from the nationwide, population-based cohort of the REACTION study. The International Physical Activity Questionnaire was used to measure self-reported time for sleeping, sitting, walking and moderate-to-vigorous physical activity (MVPA). MAFLD was defined by evidence of fatty liver index (FLI) ≥ 60 in addition to one of the following three patterns, namely overweight/obesity, presence of diabetes, or evidence of metabolic dysregulation. Isotemporal substitution models using logistic regression models to evaluate the association of replacement of different behaviour patterns with each other and the risk of MAFLD. RESULTS: Substitution of 60 minutes per day of sleeping, walking or total MVPA for sitting was associated with a 2%-8% reduction of MAFLD risk in overall participants. In employed individuals, replacing sitting time with occupational MVPA or nonoccupational MVPA both could bring benefits to liver steatosis. Stratified analysis found that replacing 60 minutes of sitting time with an equivalent time of other behaviour pattern could reduce approximately 8% of the risk among MAFLD participants with metabolic abnormalities. Such a relationship might be explained by the important mediated role of metabolic elements, such as waist circumference, body mass index, triglycerides and homoeostasis model assessment of insulin resistance. Furthermore, replacing sitting with MVPA showed a stronger association among participants who got enough sleep (sleep duration ≥7 hours per day). CONCLUSION: Replacing sitting with other behaviour patterns could reduce the prevalence of MAFLD, and such substitution effect was much remarkably in individuals with abnormal metabolic status. Observably, obese individuals were more likely to benefit from appropriate changes in behaviour patterns. Moreover, the analysis of sleep duration stratification appealed that the adequacy of individual sleep duration also had a significant impact on the substitution effect. It is worth noting that adjusting the time allocation of behaviour patterns might have a beneficial impact on liver-metabolic health, and these findings might help us better recognize the importance of reasonable arrangement of behaviour patterns according to the individual's situation.

Association of soy food with cardiovascular outcomes and all-cause mortality in a Chinese population: a nationwide prospective cohort study.

PURPOSE: This study aimed to clarify the association of soy intake with cardiovascular disease (CVD) and all-cause mortality. METHODS: We conducted a prospective cohort study in a Chinese population composed of 97,930 participants aged ≥ 40 years old without CVD at baseline in 2011. Habitual soy intake over a period of 12 months was evaluated using a food frequency questionnaire. All participants were classified into four groups based on their soy food consumption levels: < 15, 15-29, 30-59, and ≥ 60 g/day, with the lowest category as the reference group. Follow-up was conducted between 2014 and 2016 to assess CVD incidence and all-cause mortality since baseline, which was collected from the local mortality and disease registers of the National Disease Surveillance Point System and National Health Insurance System. The Cox proportional hazards regression models were used to analyze the relationship of soy intake with later CVD events and all-cause mortality. RESULTS: During 350,604 person-years of follow-up (median [interquartile range]: 3.16 [2.98, 4.77] years), 2523 total CVD events and 1473 all-cause mortalities were documented. After controlling for covariates, the hazard ratios (95% confidence intervals) for total CVD events across increasing soy intake levels were 1.03 (0.93-1.14); 0.96 (0.86-1.07); and 0.86 (0.75-0.98; p for trend = 0.0434), while those for all-cause mortality were 0.88 (0.77-1.02); 0.86 (0.74-1.00); and 0.83 (0.69-0.99; p for trend = 0.0084). CONCLUSION: High soy intake was associated with a reduced risk of total CVD events and all-cause mortality among a Chinese population.

Age-specific disparity in life loss per death attributable to ambient temperature: A nationwide time-series study in China.

Age-specific discrepancy of mortality burden attributed to temperature, measured as years of life lost (YLL), has been rarely investigated. We investigated age-specific temperature-YLL rates (per 100,000) relationships and quantified YLL per death caused by non-optimal temperature in China. We collected daily meteorological data, population data and daily death counts from 364 locations in China during 2006-2017. YLL was divided into three age groups (0-64 years, 65-74 years, and ≥75 years). A distributed lag non-linear model was first employed to estimate the associations of temperature with age-specific YLL rates in each location. Then we pooled the associations using a multivariate meta-analysis. Finally, we calculated age-specific average YLL per death caused by temperature by cause of death and region. We observed greater effects of cold and hot temperature on YLL rates for the elderly compared with the young population by region or cause of death. However, YLL per death due to non-optimal temperature for different regions or causes of death decreased with age, with 2.0 (95 % CI:1.5, 2.5), 1.2 (1.1, 1.4) and 1.0 years (0.9, 1.2) life loss per death for populations aged 0-64 years, 65-74 years and over 75 years, respectively. Most life loss per death results from moderate temperature, especially moderate cold for all age groups. The effect of non-optimal temperature on YLL rates is smaller for younger populations than older ones, while the temperature-related life loss per death was more prominent for younger populations.

Cardiovascular Risk Based on ASCVD and KDIGO Categories in Chinese Adults: A Nationwide, Population-Based, Prospective Cohort Study.

BACKGROUND: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline used eGFR and urinary albumin-creatinine ratio (ACR) to categorize risks for CKD prognosis. The utility of KDIGO's stratification of major CVD risks and predictive ability beyond traditional CVD risk prediction scores are unknown. METHODS: To evaluate CVD risks on the basis of ACR and eGFR (individually, together, and in combination using the KDIGO risk categories) and with the atherosclerotic cardiovascular disease (ASCVD) score, we studied 115,366 participants in the China Cardiometabolic Disease and Cancer Cohort study. Participants (aged ≥40 years and without a history of cardiovascular disease) were examined prospectively for major CVD events, including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. RESULTS: During 415,111 person-years of follow-up, 2866 major CVD events occurred. Incidence rates and multivariable-adjusted hazard ratios of CVD events increased significantly across the KDIGO risk categories in ASCVD risk strata (all P values for log-rank test and most P values for trend in Cox regression analysis <0.01). Increases in c statistic for CVD risk prediction were 0.01 (0.01 to 0.02) in the overall study population and 0.03 (0.01 to 0.04) in participants with diabetes, after adding eGFR and log(ACR) to a model including the ASCVD risk score. In addition, adding eGFR and log(ACR) to a model with the ASCVD score resulted in significantly improved reclassification of CVD risks (net reclassification improvements, 4.78%; 95% confidence interval, 3.03% to 6.41%). CONCLUSIONS: Urinary ACR and eGFR (individually, together, and in combination using KDIGO risk categories) may be important nontraditional risk factors in stratifying and predicting major CVD events in the Chinese population.

High concentrations of triglycerides are associated with diabetic kidney disease in new-onset type 2 diabetes in China: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

AIMS: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. METHODS: In total, 11 142 patients with new-onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011-2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow-up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow-up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high-density lipoprotein cholesterol (HDL-c) was defined by HDL-c <1.0 mmol/L for men or <1.3 mmol/L for women. RESULTS: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL-c at both baseline and follow-up visits. The DKD group also had higher levels of post-load plasma glucose and TG at follow-up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p = .012) and high TG at follow-up (OR = 1.71, p < .001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow-up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p < .001) after adjustment for covariates. CONCLUSIONS: In a large population of patients with new-onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD.

The association between diabetes and thyroid cancer risk: a hospital-based case-control study in China.

BACKGROUND: Previous studies have indicated inconsistent relationships of diabetes with thyroid cancer risk, yet little is known in China. In this study, we aimed to investigate the associations between diabetes, diabetes duration and the risk of thyroid cancer in Chinese population. METHODS: A 1:1 matched case-control study was performed between 2015 and 2017 in Zhejiang Province including 2,937 thyroid cancer cases and 2,937 healthy controls. Odds ratios (ORs) with 95 % confidence intervals (CIs) for thyroid cancer were estimated in logistic regression models. Specific effects stratified by age, as well as sex, body mass index (BMI) and family history of diabetes were also examined. RESULTS: Overall, neither diabetes (OR = 0.75, 95 % CI: 0.21-2.73) nor diabetes duration (OR = 0.14, 95 % CI: 0.02-1.22 for diabetes duration ≦ 5 years; OR = 2.10, 95 % CI: 0.32-13.94 for diabetes duration > 5 years) was significantly associated with thyroid cancer. In stratified analyses, significant lower risk of thyroid cancer was observed among subjects with diabetes and shorter diabetes duration ( ≦ 5 years), but limited to those who were aged more than 40 years, female, overweight/obese and had positive family history of diabetes. CONCLUSIONS: Diabetes and shorter diabetes duration were significantly associated with decreased risk of thyroid cancer in individuals characterized by older age, female sex, higher BMI and positive family history of diabetes.

Menstrual, reproductive and hormonal factors and thyroid cancer: a hospital-based case-control study in China.

BACKGROUND: There have been considerable studies on the effects of reproductive factors on thyroid cancer risk, while findings are inconsistent. In this analysis, we aimed to investigate the associations between menstrual, reproductive and hormonal factors with thyroid cancer occurrence in a population of Chinese women. METHODS: Using data from a 1:1 matched case-control study performed between 2015 and 2017 in Zhejiang Province of China, a second analysis of 2261 pairs of female subjects was conducted. The possible effects for thyroid cancer were evaluated in logistic regression models by odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Later age at first pregnancy (for > 25 vs. ≦ 20 years, OR: 0.47, 95% CI 0.23-0.96) and longer duration of breast feeding (for 6-12 vs. ≦ 6 months, OR: 0.49, 95% CI 0.24-0.98) were significantly associated with decreased occurrence of thyroid cancer, while no trend was observed. Stratified by age at enrollment, only the association with duration of breast feeding remained significant, but limited to younger women (≦ 50 years). CONCLUSIONS: Our results suggested that women with later age at first pregnancy or longer breast feeding duration were less likely to have thyroid cancer. These findings supported an influence role of reproductive factors in thyroid cancer risk.

Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China.

BACKGROUND: Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). METHODS: The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. FINDINGS: 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14 930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week-ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1·58, 95% CI 1·36-1·84, p<0·0001) than for ischaemic stroke (1·27, 1·13-1·43, p=0·0001). For myocardial infarction, however, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0·96, 95% CI 0·78-1·18, p=0·69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0·0001). Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or myocardial infarction. INTERPRETATION: Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction. FUNDING: Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, National Natural Science Foundation of China, British Heart Foundation, Cancer Research UK, GlaxoSmithKline, Medical Research Council, and Wellcome Trust.

Comparison of life loss per death attributable to ambient temperature among various development regions: a nationwide study in 364 locations in China.

BACKGROUND: Several studies have investigated the associations between ambient temperature and years of life lost (YLLs), but few focused on the difference of life loss attributable to temperature among different socioeconomic development levels. OBJECTIVES: We investigated the disparity in temperature-YLL rate relationships and life loss per death attributable to nonoptimal temperature in regions with various development levels. METHODS: Three hundred sixty-four Chinese counties or districts were classified into 92 high-development regions (HDRs) and 272 low-development regions (LDRs) according to socioeconomic factors of each location using K-means clustering approach. We used distributed lag non-linear models (DLNM) and multivariate meta-analysis to estimate the temperature-YLL rate relationships. We calculated attributable fraction (AF) of YLL and temperature-related average life loss per death to compare mortality burden of temperature between HDRs and LDRs. Stratified analyses were conducted by region, age, sex and cause of death. RESULTS: We found that non-optimal temperatures increased YLL rates in both HDRs and LDRs, but all subgroups in LDRs were more vulnerable. The disparity of cold effects between HDRs and LDRs was significant, while the difference in heat effect was insignificant. The overall AF of non-optimal temperature in LDRs [AF = 12.2, 95% empirical confidence interval (eCI):11.0-13.5%] was higher than that in HDRs (AF = 8.9, 95% eCI: 8.3-9.5%). Subgroups analyses found that most groups in LDRs had greater AFs than that in HDRs. The average life loss per death due to non-optimal temperature in LDRs (1.91 years, 95% eCI: 1.72-2.10) was also higher than that in HDRs (1.32 years, 95% eCI: 1.23-1.41). Most of AFs and life loss per death were caused by moderate cold in both HDRs and LDRs. CONCLUSIONS: Mortality burden caused by temperature was more significant in LDRs than that in HDRs, which means that more attention should be paid to vulnerable populations in LDRs in planning adaptive strategies.

Factors associated with glycemic control in community-dwelling elderly individuals with type 2 diabetes mellitus in Zhejiang, China: a cross-sectional study.

BACKGROUND: Although exercise seems to be beneficial for type 2 diabetes mellitus (T2DM) patients, there is limited research elucidating the optimal accessible indices of adiposity and insulin resistance for identifying elderly T2DM patients with poor glycemic control, which could be improved by performing regular exercise. METHODS: A community-based, cross-sectional study was conducted with 918 Chinese elderly individuals with T2DM in Zhejiang. Relevant risk factors for poor glycemic control, as determined using glycated haemoglobin A1c (HbA1c) > 7%, were explored using logistic regression analyses and included body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), the product of fasting triglycerides and glucose (TyG), visceral adiposity index (VAI), lipid accumulation product (LAP), TyG-BMI, and TyG-WC. Comparisons of the risk factors' ability to discriminate poor glycemic control as well as their optimal cutoff values were determined using receiver operating characteristic (ROC) analyses, and then the extent of poor glycemic control risk reduction through regular exercise was examined using multivariate logistic regression analyses. RESULTS: The overall poor glycemic control rate was 49.3%. The factors associated with poor glycemic control included FBG > 3.869, TyG > 8.73, TyG-BMI > 222.45, and TyG-WC > 713.48 in logistic regression analyses. The optimal cutoff points of FBG, TyG, TyG-WC, and TyG-BMI in discriminating poor glycemic control were 7.38, 9.22, 813.33, and 227.77, and their corresponding areas under the ROC curves were 0.864(0.840-0.886), 0.684(0.653-0.714), 0.604(0.571-0.635), and 0.574(0.541-0.606), respectively. Occasional and regular exercise reduced the odds ratios (95% confidence interval) of poor glycemic control to 0.187 (0.063-0.557) and 0.183 (0.059-0.571) for subjects with TyG-WC > 813.33 (p = 0.008), to 0.349 (0.156-0.782) and 0.284 (0.123-0.652) for subjects with TyG > 9.22 (p = 0.011), and to 0.390 (0.175-0.869) and 0.300(0.130-0.688) for subjects with TyG-BMI > 227.77 (p = 0.017), respectively, after adjusting for multiple confounding factors. CONCLUSION: Among elderly individuals with T2DM, poor glycemic control risk might be identified using indices calculated from FBG, TG, BMI, and WC measurements, which are indicative of adiposity and insulin resistance. TyG-WC seems to be an accessible and useful indicator to identify which elderly T2DM patients would benefit from performing regular exercise to achieve good glycemic control.

Analysis of differential expression profile of miRNA in peripheral blood of patients with lung cancer.

PURPOSE: To identify potential molecular targets for lung cancer intervention and diagnosis, we analyzed the differential miRNA expression of peripheral blood between lung cancer patients and healthy controls. METHODS: Three pairs of cases' and controls' peripheral blood samples were evaluated for miRNA expression by microarray. 12 miRNAs were selected for RT-PCR validation and target genes prediction. In addition, 4 miRNAs were selected for future validation by RT-PCR in a large sample of 145 cases and 55 frequency-matched healthy controls. RESULTS: A total of 338 differentially expressed miRNAs were screened and identified by microarray. According to the fold changes, the top ten upregulated miRNAs were hsa-miR-124-3p, hsa-miR-379-5p, hsa-miR-3655, hsa-miR-450b-5p, hsa-miR-29a-5p, hsa-miR-200a-3p, hsa-miR-542-3p, hsa-miR-138-5p, hsa-miR-219a-2-3p, and hsa-miR-4701-3p, and the top ten downregulated miRNAs were hsa-miR-34c-5p, hsa-miR-135a-5p, hsa-miR-132-3p, hsa-miR-3178, hsa-miR-4449, hsa-miR-4999-3p, hsa-miR-1246, hsa-miR-4424, hsa-miR-1252-5p, and hsa-miR-24-2-5p. RT-PCR verification of the 12 miRNAs revealed that 5 of 8 upregulated miRNAs, 2 of 4 downregulated miRNAs showed a significant difference between the cases and controls (P < .05). A large number of target genes and their functional set showed overlapping among the 453 predicted target genes of the 12 miRNAs (P < .01). RT-PCR in the large sample confirmed the significant differential expression level of hsa-miR-29a-5p, hsa-miR-135a-5p, hsa-miR-542-3p, and hsa-miR-4491 between cases and controls (P < .05), and three of these microRNA, except hsa-miR-29a-5p, were significant after Bonferroni correction for adjustment of multiple comparisons. CONCLUSION: There was a significant difference in miRNAs expression in the peripheral blood between lung cancer patients and healthy controls, and 4 miRNAs were validated by a large-size sample.

CYP2E1 and GSTM1 gene polymorphisms, environmental factors, and the susceptibility to lung cancer.

OBJECTIVE: To investigate the relationships between the CYP2E1 RsaI polymorphism, GSTM1 polymorphism, and the susceptibility to lung cancer, along with the interactions between environmental factors and these genes. METHODS: A case-control study was carried out to explore the independent effect of gene polymorphisms on risk of lung cancer, and the combined effects of gene loci. The stratification analysis of age, sex, smoking, and drinking combined with positive loci was also analyzed, and any interaction was identified. RESULTS: The logistic regression analysis showed that there were statistical relationships between the CYP2E1 RsaI TT genotype and lung cancer, GSTM1 (-) and lung cancer. The combined effect's analysis of these 2 loci showed that, with an increase in the number of risk alleles, the risk of lung cancer also increased (supposing 0 risk allele as the reference group). Subjects carrying 3 risk alleles had the highest risk of developing lung cancer with an adjusted OR = 10.38 (95% CI 2.10-51.35). Stratified analysis showed that, in women, nonsmoking subjects, or nondrinking subjects, the combined effects could increase the risk of lung cancer; no heterogeneity was found between these layers except sex. The interaction analysis showed that, supposing the male, GSTM1 (+) genotype as the reference, the female, GSTM1 (-) genotype had a significantly increased risk of lung cancer (OR = 2.17 [1.01-4.70]); when the non-smoking, GSTM1 (+) genotype subjects was the reference group, smoking, GSTM1 (+) genotype subjects and smoking, GSTM1 (-) genotype subjects had significantly higher risk of lung cancer (OR = 2.00 [1.01-3.96], OR = 2.89 [1.28-6.54]). CONCLUSION: CYP2E1 RsaI TT genotype was a protective factor against the development of lung cancer, while GSTM1 (-) genotype was a risk factor for lung cancer. Increases in the number of the risk alleles also increased lung cancer risk. GSTM1 (-) genotype, sex, and smoking status might interact in the incidence of lung cancer.

Gender disparity in the associations of overweight/obesity with occupational activity, transport to/from work, leisure-time physical activity, and leisure-time spent sitting in working adults: A cross-sectional study.

BACKGROUND: The associations of occupational activity (OA), commuting, leisure-time physical activity (LTPA), and sitting with overweight/obesity in working adults are controversial. This study explored these factors with the risk of overall and abdominal overweight/obesity in a Chinese working population and whether these associations differ by gender. METHODS: A cross-sectional study was conducted. Data analysis was done among 6739 employed participants. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the studied associations. RESULTS: For male employees, those with heavy OA had a lower overall (OR 0.76; 95% CI, 0.62-0.93) and abdominal (OR 0.76; 95% CI, 0.62-0.93) overweight/obesity risk than those with light OA. Those with LTPA ≥150 min/week had a lower risk of overall (OR 0.73; 95% CI, 0.56-0.96) and abdominal (OR 0.70; 95% CI, 0.53-0.91) overweight/obesity than those with LTPA <150 min/week. Men with leisure-sitting time <2.5 h/day had a significantly lower risk of abdominal overweight/obesity than those sitting ≥4 h/day (OR 0.80; 95% CI, 0.65-0.99). And men who cycled to/from work had a lower risk of overall (OR 0.69; 95% CI, 0.53-0.90) and abdominal overweight/obesity (OR 0.71; 95% CI, 0.54-0.92) than passive transports. However, the above significant associations disappeared among female employees. CONCLUSIONS: Heavy OA, cycling to/from work, and LTPA were associated with lower risk of overall or abdominal overweight/obesity in male employees. Reducing leisure sitting time can also help male employees reduce the risk of abdominal overweight/obesity. More research on gender disparity in the risk of overweight and obesity should be done.

Impact of injury-related mortality on life expectancy in Zhejiang, China based on death and population surveillance data.

BACKGROUND: Life expectancy is a statistical measure of the average time an organism is expected to live. The purpose of this study was to evaluate the impact of injury-related mortality on life expectancy in Zhejiang Province. METHODS: Our study used standard life tables to calculate life expectancy and cause-removed life expectancy based on mortality data from the Zhejiang Chronic Disease Surveillance System. RESULTS: Life expectancy of residents in Zhejiang was 77.83 years in 2013, with females having a higher life expectancy than males. The decrease in life expectancy caused by injury-related deaths was 1.19 years, the effect of which was reduced for females and urban residents compared with males and rural residents. The greatest impact on life expectancy was road traffic injuries (RTIs), (0.29 years lost overall, 0.36 for men vs. 0.21 for women and 0.26 for urban residents vs. 0.31 for rural residents). The main causes were falls (0.29 years lost overall, 0.30 for men vs. 0.28 for women and 0.28 for urban residents vs. 0.30 for rural residents), followed by drowning (0.15 years lost), suicide (0.11 years lost), and poisoning (0.04 years). For children less than 5 years old and elders aged over 65, drowning had a greater impact than falls. CONCLUSIONS: Our findings indicate that injury deaths had a major impact on life expectancy in Zhejiang. More attention should be paid to road traffic injury, and preventive action should be taken to reduce injury-related deaths to increase life expectancy, especially in children under five years of age and the elders over 65 years of age.