Cost-Effectiveness of a Workplace-Based Hypertension Management Program in Real-World Practice in the Kailuan Study.

BACKGROUND: In 2009, a workplace-based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost-effectiveness of this program remains unclear. METHODS AND RESULTS: This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10-year follow-up data, we estimated costs, quality-adjusted life years (QALYs), life-years, and incremental cost-effectiveness ratios (ICERs) for workplace-based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10-year follow-up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life-years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost-effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life-year gained, respectively, when comparing workplace-based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness-to-pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost-effective in 10 000 samples. CONCLUSIONS: Workplace-based management, compared with routine care for Chinese men with hypertension, could be cost-effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016.

BACKGROUND: Although adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. OBJECTIVES: We aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. METHODS: We conducted cross-sectional analyses of 2100 individuals aged 6-18 y enrolled in the National Health and Nutrition Examination Survey, 2011-2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. RESULTS: In multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [ß: -1.566; 95% confidence interval: -2.935, -0.196], 1.423 (-1.423; -2.689, -0.157), 1.309 (-1.309; -2.573, -0.044), 1.530 (-1.530; -2.918, -0.142), and 1.381 (-1.381; -2.641, -0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (-0.888; -1.677, -0.099) ng/mL decrease in the serum folate. CONCLUSIONS: Higher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Sex-specific associations between skeletal muscle mass and incident diabetes: A population-based cohort study.

AIMS: To investigate the sex-specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. MATERIALS AND METHODS: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check-up-based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self-reported history to identify new-onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. RESULTS: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5-year median follow-up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). CONCLUSIONS: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass.

Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.

AIMS: To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. METHODS: Serum FGF21 levels were measured at 6-15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. RESULTS: Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction = 0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24 kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24 kg/m2 ) and FGF21 levels (≥median and

Exposure to Trihalomethanes and Bone Mineral Density in US Adolescents: A Cross-Sectional Study (NHANES).

Animal and human studies have suggested that trihalomethane (THM) has toxicity to bone. In this study, we included adolescents from the National Health and Nutrition Examination Survey who had quantified blood and tap water THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and lumbar spine or total body less head (TBLH) bone mineral density (BMD). A 2.7-fold increase in concentrations of blood TCM, DBCM, chlorinated THMs (the sum of TCM, BDCM, and DBCM), and total THMs (the sum of 4 THMs) was associated with lower lumbar spine BMD z-scores by -0.06 [95% confidence interval (CI): -0.12, -0.01], -0.06 (95% CI: -0.11, -0.003), -0.08 (95% CI: -0.14, -0.02), and -0.07 (95% CI: -0.13, -0.003), respectively, in adjusted models. Similarly, a 2.7-fold increase in blood BDCM, DBCM, and chlorinated THM concentrations was associated with lower TBLH BMD z-scores by -0.10 (95% CI: -0.17, -0.02), -0.10 (95% CI: -0.17, -0.03), and -0.11 (95% CI: -0.20, -0.01), respectively. Low-to-moderate predictive power was attained when tap water THM concentrations were used to predict blood THM measurements. Notably, the inverse associations for blood THMs persisted exclusively between water concentrations of DBCM and Br-THMs and the TBLH BMD z-scores. Our findings suggest that exposure to THMs may adversely affect the adolescent BMD.

Metal Exposure during Early Pregnancy and Risk of Gestational Diabetes Mellitus: Mixture Effect and Mediation by Phospholipid Fatty Acids.

Despite existing studies exploring the association between metal exposure and gestational diabetes mellitus (GDM), most of them have focused on a single metal or a small mixture of metals. Our prospective work investigated the joint and independent effects of early gestational exposure to 17 essential and nonessential metals on the GDM risk and potential mediation by plasma phospholipid fatty acids (PLFAs) based on a nested case-control study established with 335 GDM cases and 670 randomly matched healthy controls. The Bayesian kernel machine regression (BKMR) and quantile g-computation analyses demonstrated a joint effect from metal co-exposure on GDM risk. BKMR with hierarchical variable selection indicated that the group of essential metals was more strongly associated with GDM than the group of nonessential metals with group posterior inclusion probabilities (PIPs) of 0.979 and 0.672, respectively. Cu (0.988) and Ga (0.570) had the largest conditional PIPs within each group. We also observed significant mediation effects of selected unsaturated PLFAs on Cu-GDM and Ga-GDM associations. KEGG enrichment analysis further revealed significant enrichment in the biosynthesis of unsaturated PLFAs. C18:1 n-7 exhibited the largest proportion of mediation in both associations (23.8 and 22.9%). Collectively, our work demonstrated the joint effect of early gestational metal exposure on GDM risk and identified Cu and Ga as the key species to the joint effect. The findings lay a solid ground for further validation through multicenter investigations and mechanism exploration via laboratory studies.

Effects of Sample Dilution on Nuclear Magnetic Resonance-Derived Metabolic Profiles of Human Urine.

Traditionally, a relatively big urine volume (e.g., 500 µL) is used in nuclear magnetic resonance (NMR)-based human metabolomics, which is not feasible for studies with limited/precious samples. Although urine may be diluted before conventional high-throughput metabolomics analysis, the comprehensive effect of urine dilution on metabolic profiles is unknown. Here, for the first time, we systematically investigated the effect of urine dilution on 1H NMR metabolic profiles, by evaluating signal detectability, integration, signal-to-noise ratio (SNR), chemical shift (δ) and its variation, and signal overlapping of 47 metabolites in 10 volunteers. We observed significant linear changes along with increased dilution, including decreased integration and SNR, altered δ, decreased intersample variation of δ, and increased separation between overlapped signals, e.g., lactate and threonine, ß-d-glucose and an unassigned signal, and histidine and 3-methylhistidine. We further tested the 40% dilution level (i.e., employing 300 µL urine) in an epidemiological study containing 1018 pregnant women from the Tongji-Shuangliu Birth Cohort, showing acceptable detectability and chemical shift variability for most of the 47 metabolites profiled. It indicated that mild (e.g., 40%) dilution of human urine can largely preserve the high-abundance metabolites profiled, reduce intersample chemical shift variations, and increase separations of overlapped signals, which is an improvement of routine sample preparation methods in NMR-based metabolomics and is applicable for studies with limited urine volumes, including large-scale epidemiological studies.

Target Exposome for Characterizing Early Gestational Exposure to Contaminants of Emerging Concern and Association with Gestational Diabetes Mellitus.

Characterization of gestational exposure to complex contaminants of emerging concern (CECs) is critical to the identification of environmental risk factors for pregnancy complications. However, determination of various CECs with diverse physicochemical properties in biological fluids is technically challenging. In the present study, we developed a target exposome protocol, consisting of simple liquid-liquid extraction-based sample preparation and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, to determine 325 CECs covering 11 subclasses, including poly- and perfluoroalkyl substances, organophosphate esters, ultraviolet (UV) stabilizers, synthetic antioxidants, phthalate esters, and several others. The protocol exhibits exceptional advantages over traditional approaches in the coverage of chemicals, sample volume demand, and time and financial cost. The protocol was applied in a prospective nested gestational diabetes mellitus (GDM) study including 120 cases and 240 matched healthy controls. Thirty-three CECs were detected in >70% of the samples, with a combined concentration of 17.0-484.7 ng/mL. Bayesian kernel machine regression analysis showed that exposure to the CEC mixture was significantly associated with a higher GDM risk. For example, when increasing all CECs in the mixture from 50th percentile to 75th percentile, the estimated probit of GDM incidence had an increase of 92% (95% CI: 56%, 127%). Meanwhile, perfluorohexanesulfonic acid, 1,3-diphenylguanidine, and dibutyl fumarate were identified as the key CECs driving the joint effect. This work demonstrates great potential of our target exposome protocol for environmental risk factor identification in large-scale epidemiology or biomonitoring studies.

Consumption of ultra-processed foods and all-cause and cause-specific mortality in the Southern Community Cohort Study.

BACKGROUND & AIMS: Higher intake of ultra-processed foods (UPF) has been linked with higher risks of cancer, cardiovascular disease, and diabetes, as well as all-cause mortality. However, studies on UPF and cause-specific mortality remain limited, especially among disadvantaged populations. We aimed to examine associations of UPF intake with all-cause and cause-specific mortality among low-income Americans. METHODS: In the Southern Community Cohort Study (SCCS), a prospective cohort of mostly low-income Black and White Americans, we included 77,060 participants who completed a food frequency questionnaire (FFQ) at baseline (2002-2009) and had at least 1 year follow-up. All 89 items in the FFQ were categorized using the Nova classification. UPF intake was calculated as % of daily foods intake by weight (grams). Cox regression was used to estimate HR (95% CI) for the association of UPF intake (quartile or per 10% increase) with total and cause-specific mortality (cancer, coronary heart disease [CHD], stroke, and diabetes) after adjusting for sociodemographics, lifestyles, and disease history. RESULTS: Of 77,060 participants, 46,175 (59.9%) were women, 49,857 were Black (64.7%), and mean age was 52.4 (SD: 8.8) years at baseline. The mean intake of UPF was 41.0% (SD: 15.7%). UPF intake was inversely associated with Healthy Eating Index and intakes of fiber, minerals, and vitamins but positively associated with intakes of sugars and fats (all PFDR<0.0001). During an average follow-up of 12.2 years, we documented 17,895 total deaths, including 4267 from cancer, 2208 from CHD, 867 from stroke, and 997 from diabetes. In the fully adjusted model, higher UPF intake was not associated with all-cause, cancer, CHD, or stroke mortality but showed a significant association with increased diabetes mortality (HR [95% CI] = 1.32 [1.07, 1.62] for the highest versus lowest quartiles [>51.1% vs. <29.3%] and 1.09 [1.04, 1.15] per 10% increase). The adverse UPF-diabetes mortality association was noted regardless of sex, race, income, neighborhood deprivation, lifestyles, and cardiometabolic disease history, while particularly evident in participants with no more than high school education or a history of hypercholesterolemia (HR [95% CI] per 10% increase = 1.12 [1.05, 1.18] and 1.14 [1.07, 1.22], respectively; both Pinteraction<0.05). CONCLUSIONS: Among predominantly low-income Black and White American adults, UPF intake was associated with increased diabetes mortality, especially for individuals with limited education or hypercholesterolemia. Our findings suggest the potential impact of increasing access and intake of un/minimally processed food to replace UPF on reducing diabetes-related mortality among populations facing socioeconomic and health disparities.

Blood Cell Parameters From Early to Middle Pregnancy and Risk of Gestational Diabetes Mellitus.

CONTEXT: Chronic low-grade inflammation may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, prospective studies on the relations of inflammatory blood cell parameters during pregnancy with GDM are lacking. OBJECTIVE: To prospectively investigate the associations of inflammatory blood cell parameters in both early and middle pregnancy, and their change patterns from early to middle pregnancy, with GDM risk. METHODS: We used data from the Tongji-Shuangliu Birth Cohort. Inflammatory blood cell parameters (white blood cells [WBC], neutrophils, lymphocytes, monocytes, neutrophil to lymphocyte ratio [NLR], and platelets) were assayed before 15 weeks and between 16 and 28 weeks of gestational age. Logistic regression was used to evaluate the associations between inflammatory blood cell parameters and GDM. RESULTS: Of the 6354 pregnant women, 445 were diagnosed with GDM. After adjustment for potential confounders, WBC, neutrophils, lymphocytes, monocytes, and NLR in early pregnancy were positively associated with GDM risk (odds ratios [95% CI] for extreme-quartile comparison were 2.38 [1.76-3.20], 2.47 [1.82-3.36], 1.40 [1.06-1.85], 1.69 [1.27-2.24], and 1.51 [1.12-2.02], respectively, all P for trend ≤ .010). Similarly, higher levels of WBC, neutrophils, monocytes, and NLR in middle pregnancy were associated with increased risk of GDM (all P for trend ≤ .014). Stable high levels (≥ median in both early and middle pregnancy) of WBC, neutrophils, monocytes, and NLR were positively associated with GDM risk (all P ≤ .001). CONCLUSION: Increased WBC, neutrophils, monocytes, and NLR in both early and middle pregnancy and their stable high levels from early to middle pregnancy were associated with higher GDM risk, highlighting that they might be clinically relevant for identifying individuals at high risk for GDM.

High quality diet attenuated the positive association between polychlorinated biphenyls and premature mortality among middle-aged and older adults.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have been reported to be a risk factor for premature death, while a high diet quality is thought to lower mortality risk. We aimed to examine whether PCBs were associated with higher all-cause and cause-specific mortality risk and whether such associations could be modified by the diet quality among US middle-aged and older adults. METHODS: Included were 1259 participants aged 40 years or older from the 1999-2004 National Health and Nutrition Examination surveys. Exposure to PCBs was assessed in non-fasting serum samples, and mortality status was ascertained through December 31, 2019 using the public-use, linked mortality files. Diet quality was assessed using the Healthy Eating Index-2015 based on 24-h dietary recalls. Cox proportional hazard regression was applied to assess the associations of different PCB congener groups with mortality and the modifying effect by the diet quality. RESULTS: During a median follow-up of 17.75 years, 419 deaths occurred, including 131 from cardiovascular disease (CVD) and 102 from cancer. Serum concentrations of dioxin-like PCBs and non-dioxin-like PCBs were significantly associated with all-cause mortality, with hazard ratios (HRs) of 1.84 (95% confidence interval [CI], 1.10, 2.99) and 1.82 (1.09, 3.03) for extreme-tertile comparisons. A significant interaction was noted between dioxin-like PCBs and diet quality (P for interaction: 0.012), with a substantially more pronounced association among participants with a low diet quality (HR, 3.47; 95% CI: 1.29, 9.32), compared to those with a high diet quality (HR, 0.98; 95% CI: 0.40, 2.43). A similar weaker association was observed for total PCBs in participants with a high diet quality (P for interaction: 0.032). However, effect modifications by diet quality were not noted for the associations between different PCB groups and CVD mortality. CONCLUSIONS: While our findings need to be validated in other populations and mechanistic studies, they may suggest that a high quality diet could potentially attenuate the harmful effects of chronic PCB exposure.

The relationship between physical activity in early pregnancy and hypertensive disorders of pregnancy: a cohort study in Chinese women.

BACKGROUND: We aimed to examine prospective associations between different intensities and different types of physical activity (PA) in early pregnancy and hypertensive disorders of pregnancy (HDP) among Chinese women. METHODS: A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study. The pregnancy physical activity questionnaire (PPAQ) was used to assess PA, including household/caregiving, occupational, sports/exercise, and transportation activities in the first trimester of pregnancy. The diagnosis of HDP was collected, including gestational hypertension (GH) and preeclampsia (PE). Data were analyzed by unconditional multivariate logistic regression, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 178 (2.6%) of the 6,820 women were diagnosed with HDP, of which 126 (1.8%) were GH and 52 (0.8%) were PE. Overall, we found no association between PA in early pregnancy and PE. A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity (MVPA) (adjusted OR 0.54, 95% CI 0.31-0.96). No association was observed between PA and HDP in early pregnancy, regardless of different intensities or types of PA. CONCLUSION: MVPA in the first trimester is an influencing factor of HDP. Encouraging pregnant women to engage in MVPA in the first trimester may help to prevent GH.

Combined healthy lifestyle in early pregnancy and risk of gestational diabetes mellitus: A prospective cohort study.

OBJECTIVE: To examine the association of a combined healthy lifestyle in early pregnancy with gestational diabetes mellitus (GDM) risk. DESIGN, SETTING AND POPULATION: A Chinese prospective cohort study with 6980 pregnant women. METHODS: Individual modifiable lifestyle factors were assessed in early pregnancy and a combined lifestyle score was derived from the sum of the lifestyle factors, with a higher score indicating a healthier lifestyle. The association of a combined healthy lifestyle with GDM risk was examined. MAIN OUTCOME MEASURES: Gestational diabetes mellitus was diagnosed in middle pregnancy according to the International Association of Diabetes and Pregnancy Study Group criteria or diagnoses in medical records. RESULTS: Overall, 501 (7.2%) pregnant women were diagnosed with GDM. Being physically active (total energy expenditure in upper three quintiles, i.e. ≥100.1 metabolic equivalent of task [MET]-hours/week; odds ratio [OR] 0.76, 95% confidence interval [CI] 0.63-0.92), healthy diet (total intake of vegetables and fruits ≥5 times/day; OR 0.74, 95% CI 0.59-0.94), sufficient sleep (night-time sleep duration ≥7 hours/night; OR 0.66, 95% CI 0.48-0.90) and healthy weight (early-pregnancy BMI <24.0 kg/m2 ; OR 0.57, 95% CI 0.46-0.71) were associated with lower GDM risk. The GDM risk decreased linearly across the combined lifestyle score (Ptrend <0.001): women with 2, 3 and 4 lifestyle factors compared with those with 0-1 factor had 38% (OR 0.62, 95% CI 0.46-0.84), 57% (OR 0.43, 95% CI 0.31-0.58) and 66% (OR 0.34, 95% CI 0.22-0.52) lower risks of GDM, respectively. CONCLUSION: A healthy lifestyle in early pregnancy was associated with a substantially lower GDM risk.

Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women.

BACKGROUND: Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. METHODS: In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. RESULTS: Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. CONCLUSIONS: Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.

Association between Prepregnancy Weight Change and Risk of Gestational Diabetes Mellitus in Chinese Pregnant Women.

BACKGROUND: Evidence regarding prepregnancy weight change and gestational diabetes mellitus (GDM) is lacking among East Asian women. OBJECTIVES: Our study aimed to investigate the association between weight change from age 18 y to pregnancy and GDM in Chinese pregnant women. METHODS: Our analyses included 6972 pregnant women from the Tongji-Shuangliu Birth Cohort. Body weights were recalled for age 18 y and the time point immediately before pregnancy, whereas height was measured during early pregnancy. Prepregnancy weight change was calculated as the difference between weight immediately before pregnancy and weight at age 18 y. GDM outcomes were ascertained by 75-g oral-glucose-tolerance test. Multivariable logistic regression models were used to examine the association between prepregnancy weight change and risk of GDM. RESULTS: In total, 501 (7.2%) developed GDM in the cohort. After multivariable adjustments, prepregnancy weight change was linearly associated with a higher risk of GDM (P < 0.001). Compared with participants with stable weight (weight change within 5.0 kg) before pregnancy, multivariable-adjusted odds ratios and 95% confidence intervals were 1.55 (1.22, 1.98) and 2.24 (1.78, 2.83) for participants with moderate (5-9.9 kg) and high (≥10 kg) weight gain, respectively. In addition, overweight/obesity immediately before pregnancy mediated 17.6% and 31.7% of the associations of moderate and high-weight gain with GDM risk, whereas weekly weight gain during pregnancy mediated 21.1% and 22.7% of the associations. CONCLUSIONS: Weight gain from age 18 y to pregnancy was significantly associated with a higher risk of GDM. Maintaining weight stability, especially prevention of excessive weight gain from early adulthood to pregnancy, could be a potential strategy to reduce GDM risk.

The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome.

BACKGROUND: Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain. METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics. RESULTS: Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02-1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01-1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses. CONCLUSIONS: Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.

The Gut Microbiome Dynamically Associates with Host Glucose Metabolism throughout Pregnancy: Longitudinal Findings from a Matched Case-Control Study of Gestational Diabetes Mellitus.

Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM-related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber-rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study.

OBJECTIVE: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. PATIENTS AND METHODS: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. RESULTS: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. CONCLUSION: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.