Tianyi Huang

Urinary Phthalate Metabolite Concentrations and Diabetes among Women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women. Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study. Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001–2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment–estimated insulin resistance, and glycosylated hemoglobin A1c. Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance. Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Intake of dietary flavonoids and risk of epithelial ovarian cancer

Background: The impact of different dietary flavonoid subclasses on risk of epithelial ovarian cancer is unclear, with limited previous studies that have focused on only a few compounds. Objective: We prospectively examined associations between habitual flavonoid subclass intake and risk of ovarian cancer. Design: We followed 171,940 Nurses’ Health Study and Nurses’ Health Study II participants to examine associations between intakes of total flavonoids and their subclasses (flavanones, flavonols, anthocyanins, flavan-3-ols, flavones, and polymeric flavonoids) and risk of ovarian cancer by using Cox proportional hazards models. Intake was calculated from validated food-frequency questionnaires collected every 4 y. Results: During 16–22 y of follow-up, 723 cases of ovarian cancer were confirmed through medical records. In pooled multivariate-adjusted analyses, total flavonoids were not statistically significantly associated with ovarian cancer risk (HR for the top compared with the bottom quintile: 0.85; 95% CI: 0.66, 1.09; P-trend = 0.17). However, participants in the highest quintiles of flavonol and flavanone intakes had modestly lower risk of ovarian cancer than did participants in the lowest quintile, although the P-trend was not significant [HRs: 0.76 (95% CI: 0.59, 0.98; P-trend = 0.11) and 0.79 (95% CI: 0.63,1.00; P-trend = 0.26), respectively]. The association for flavanone intake was stronger for serous invasive and poorly differentiated tumors (comparable HR: 0.68; 95% CI: 0.50, 0.92; P-heterogeneity = 0.10, P-trend = 0.07) compared with nonserous and less-aggressive tumors. Intakes of other subclasses were not significantly associated with risk. In food-based analyses used to compare subjects who consumed >1 and ≤1 cup black tea/d, the HR was 0.68 (95% CI: 0.51, 0.90; P < 0.01). Conclusions: Higher intakes of flavonols and flavanones as well as black tea consumption may be associated with lower risk of ovarian cancer. Additional prospective studies are required to confirm these findings.

BMI, leisure-time physical activity, and physical fitness in adults in China: results from a series of national surveys, 2000–14

BACKGROUND Obesity, physical inactivity, and reduced physical fitness contribute to the rising burden of chronic diseases in China. We investigated these factors in Chinese adults over a 14-year period (2000-14) using data from randomised national surveys. METHODS We did four national surveys in 2000, 2005, 2010, and 2014 among Chinese adults aged 20-59 years. We used BMI to assess underweight (<18·5 kg/m(2)), overweight (≥23·0 to <27·5 kg/m(2)), and obesity (≥27·5 kg/m(2)). Central obesity was defined as a waist circumference greater than 90 cm in men and greater than 85 cm in women. We assessed leisure-time physical activity (LTPA) by whether or not participants had completed the recommended minimum 150 min of moderate or 75 min of vigorous exercise per week. Indices for assessment of physical fitness were forced vital capacity, resting heart rate, hand grip strength, sit and reach distance, and time standing on one leg. FINDINGS 151 656 (78%) of 193 440 adults responded to the survey in 2000, 163 386 (84%) in 2005, 154 931 (80%) in 2010, and 146 703 (76%) in 2014. The prevalence of obesity increased from 8·6% in 2000, to 10·3% in 2005, 12·2% in 2010, and 12·9% in 2014 (estimated increase 0·32% per year, 95% CI 0·30-0·33; p<0·0001). The equivalent estimates were 37·4%, 39·2%, 40·7%, and 41·2% for overweight (estimated increase 0·27% per year, 95% CI 0·25-0·30; p<0·0001) and 13·9%, 18·3%, 22·1%, and 24·9% for central obesity (estimated increase 0·78% per year, 0·76-0·80; p<0·0001). The prevalence of overweight, obesity, and central obesity increased with age (all p<0·0001) and was higher in men than in women (all p<0·0001). We noted a simultaneous decrease in the prevalence of underweight (estimated decrease of 0·06% per year, 95% CI 0·04-0·07; p<0·0001). The proportion of adults meeting the minimum LTPA recommendation increased over time (17·2% in 2000, 18·1% in 2005, and 22·8% in 2014), with the estimated prevalence change per year being 0·33% (95% CI 0·24-0·42; p<0·0001) for underweight people, 0·50% (0·47-0·53; p<0·0001) for normal-weight people, 0·37% (0·34-0·40; p<0·0001) for overweight people, and 0·06% (0·00-0·13; p=0·044) for obese people. We noted deteriorations over time in all measures of physical fitness in normal-weight adults (all p<0·0001), apart from resting heart rate (p=0·69). INTERPRETATION Despite increased participation in LTPA, we noted increases in overweight or obesity and a decrease in physical fitness in Chinese adults. Continued nationwide interventions are needed to promote physical activity and other healthy lifestyle behaviours in China. FUNDING National Physical Fitness Surveillance Center and Ministry of Science and Technology of the Peoples Republic of China.

Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta‐Analysis of Randomized Controlled Trials

Background Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported. Methods and Results Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84–0.96; P=0.002) for stroke, 1.04 (95% CI 0.99–1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92–0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P<0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (P=0.006 for interaction) or in trials with larger reduction in homocysteine levels (P=0.009 for interaction). Conclusions Our meta‐analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.

Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors

BACKGROUND Epidemiologic studies suggest phthalate metabolite concentrations are associated with type 2 diabetes. GDM is a strong risk factor for type 2 diabetes. Little is known about phthalates and GDM risk factors (i.e. 1st trimester body mass index (BMI), gestational weight gain (GWG), and 2nd trimester glucose levels). METHODS A total of 350 women participating in Lifecodes pregnancy cohort (Boston, MA), delivered at term and had pregnancy urinary phthalate metabolite concentrations. Nine specific gravity-adjusted urinary phthalate metabolites were evaluated. General linear regression was used to assess associations between quartiles of phthalate metabolites and continuous 1st trimester BMI and late 2nd trimester blood glucose. Linear mixed models were used for total GWG. Multivariable logistic regression was used for phthalate concentrations and categorized GWG and impaired glucose tolerance defined as glucose≥140mg/dL based on a 50-gram glucose load test. Models were adjusted for potential confounders. RESULTS There were no associations between 1st trimester urinary phthalate metabolite concentrations and 1st trimester BMI. Mono-ethyl phthalate concentrations averaged across pregnancy were associated with a 2.17 increased odds of excessive GWG (95% CI: 0.98, 4.79). Second trimester mono-ethyl phthalate was associated with increased odds of impaired glucose tolerance (adj. OR: 7.18; 95% CI: 1.97, 26.15). A summary measure of di-2-ethylhexyl phthalate metabolite concentrations were inversely associated with impaired glucose tolerance (adj. OR: 0.25; adj. 95% CI: 0.08, 0.85). CONCLUSIONS Higher exposure to mono-ethyl phthalate, a metabolite of the parent compound of di-ethyl phthalate, may be associated with excessive GWG and impaired glucose tolerance; higher di-2-ethylhexyl phthalate was associated with reduced odds of impaired glucose tolerance.

Pregnancy Hyperglycaemia and Risk of Prenatal and Postpartum Depressive Symptoms.

BACKGROUND Glucose dysregulation in pregnancy may affect maternal depressive symptoms during the prenatal and postpartum periods via both physiologic and psychological pathways. METHODS During mid-pregnancy, a combination of 50-g 1-h non-fasting glucose challenge test (GCT) and 100-g 3-h fasting oral glucose tolerance test was used to determine pregnancy glycaemic status among women participating in Project Viva: normal glucose tolerance (NGT), isolated hyperglycaemia (IHG), impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). Using the Edinburgh Postnatal Depression Scale (EPDS), we assessed depressive symptoms at mid-pregnancy and again at 6 months postpartum. We used logistic regression, adjusted for sociodemographic, anthropometric and lifestyle factors, to estimate the odds of elevated prenatal and postpartum depressive symptoms (EPDS ≥ 13 on 0-30 scale) in relation to GCT glucose levels and GDM status in separate models. RESULTS A total of 9.6% of women showed prenatal and 8.4% postpartum depressive symptoms. Women with higher GCT glucose levels were at greater odds of elevated prenatal depressive symptoms [multivariable-adjusted odds ratio (OR) per standard deviation (SD) increase in glucose levels (27 mg/dL): 1.25; 95%: 1.07, 1.48]. Compared with NGT women, the association appeared stronger among women with IHG [OR: 1.80; 95% confidence interval (CI): 1.08, 3.00] than among those with GDM (OR: 1.45; 95% CI: 0.72, 2.91) or IGT (OR: 1.43; 95% CI: 0.59, 3.46). Neither glucose levels assessed from the GCT nor pregnancy glycaemic status were significantly associated with elevated postpartum depressive symptoms. CONCLUSION Pregnancy hyperglycaemia was cross-sectionally associated with higher risk of prenatal depressive symptoms, but not with postpartum depressive symptoms.

Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors: National Health and Nutrition Examination Survey (NHANES) 1999–2010:

Objectives To determine whether the associations with key risk factors in patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are different using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Methods The study analysed the prevalence and association with risk factors of undiagnosed and diagnosed T2DM using a regression model and a multinomial logistic regression model. Data from the NHANES 1999–2010 were used for the analyses. Results The study analysed data from 10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was significantly higher in non-Hispanic whites, in individuals <30 years old and in those with near optimal (130–159 mg/dl) or very high (≥220 mg/dl) non-high-density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass index, low economic status or low educational level had no effect on T2DM diagnosis rates. Though diagnosed T2DM was associated with favourable diet/carbohydrate intake behavioural changes, it had no effect on physical activity levels. Conclusion The overall T2DM prevalence increased between 1999 and 2010, particularly for undiagnosed T2DM in patients that were formerly classified as low risk.

Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies

Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full-course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (≥37 weeks) and had available urinary phthalate metabolite concentrations for ≥3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non-Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (P<0.05). When evaluating patterns by race/ethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse pregnancy and child health outcomes.

The inflammatory potential of diet and ovarian cancer risk: results from two prospective cohort studies

Background:We used a food-based empirical dietary inflammatory pattern (EDIP) score to investigate whether diets with higher inflammatory potential are associated with increased ovarian cancer risk.Methods:We followed 186 314 women in the Nurses’ Health Study and Nurses’ Health Study-II, from 1984 to 2013, to examine associations between EDIP scores and ovarian cancer risk, using Cox regression analyses.Results:During 3 454 514 person-years of follow-up, 989 ovarian cancer cases were identified. In pooled multivariable-adjusted analyses, higher EDIP scores (more pro-inflammatory diets) were not significantly associated with ovarian cancer risk (HRquintile5vs1 0.99; 95% CI: 0.80–1.22; P-trend=0.97). Similarly, we found no evidence of heterogeneity by histologic subtype (P-heterogeneity=0.52) or by tumour aggressiveness (P-heterogeneity=0.63).Conclusions:In contrast with two previous case-control studies that found a positive association between a literature-derived nutrient-based dietary inflammatory index and ovarian cancer risk, our prospective analyses using a food-based score observed no evidence of an association.

Association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c among women with Type 1 diabetes

To examine the association of pre‐pregnancy BMI and postpartum weight retention with postpartum HbA1c levels in women with Type 1 diabetes.