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Objective To investigate the association of the maternal serum albumin (MAlb) level with fetal growth and fetal growth restriction (FGR) risk in term-born singletons. Design Prospective cohort study. Setting Four hospital maternity units of the Tongji Maternal and Child Health Cohort study initiated from September 2013 to April 2016 at Wuhan City, in central China. Patient(s) A total of 3,065 mother–offspring pairs. Intervention(s) None. Main Outcome Measure(s) Fetal growth was evaluated by birth weight (BW) and birth length. Fetal growth restriction was defined as BW below the 10th percentile. Result(s) All MAlb levels were within the upper limit of normal. After adjustment for liver function parameters, inflammatory indicators, and others, a reverse U-shaped relationship between MAlb and fetal growth was observed. Specifically, BW increased significantly with an increasing MAlb level when the MAlb level was 36.1 g/L (per g/L: β = −15.1; 95% CI, −21.2, −8.9). There was a similar association between MAlb and birth length. Furthermore, the adjusted odd ratios of FGR across increasing tertiles of the MAlb levels were 1.0 (reference), 1.1 (0.7, 1.8), and 1.7 (1.0, 2.6). Conclusion(s) There was a reverse U-shaped association between MAlb and fetal growth. A higher MAlb level was associated with an increased risk of FGR. Clinical Trial Registration Number NCT03099837.

Background Breastfeeding has many established health benefits to both babies and mothers. There is limited evidence on the association between delayed lactogenesis and breastfeeding practices. Objective We assessed the association between delayed lactogenesis and breastfeeding practices in women initiating breastfeeding. Design We used data from a prospective cohort study in Wuhan, China, which enrolled pregnant women at 8-16 weeks of gestation and followed up to postpartum. Women were included who had a singleton live birth, initiated breastfeeding, and provided information on infant feeding. Maternal lactogenesis status was assessed by face-to-face interview at day 4 postpartum. Breastfeeding practices (full breastfeeding and/or any breastfeeding) were queried by telephone interview at 3, 6, and 12 mo postpartum. Poisson regression and Cox regression were used to identify the association between delayed lactogenesis and breastfeeding practices. Results Delayed lactogenesis was reported by 17.9% of the 2877 participants. After adjusting for potential confounders, when compared with timely lactogenesis, delayed lactogenesis was significantly associated with higher risk of inability to sustain full breastfeeding at 3 mo postpartum (RR: 1.24, 95% CI: 1.10, 1.39) and 6 mo postpartum (RR: 1.14, 95% CI: 1.04, 1.24). Delayed lactogenesis was also significantly associated with early termination of any breastfeeding (HR: 1.15, 95% CI: 1.01, 1.30) in the adjusted model. In a combined analysis, women with higher gestational weight gain (GWG, ≥16 kg for underweight and normal weight, 15 kg for overweight/obesity) and who subsequently experienced delayed lactogenesis had the highest risk of ending any breastfeeding earlier (adjusted HR: 1.32, 95% CI: 1.11, 1.55) compared with those who gained less GWG and experienced timely lactogenesis. Conclusions This study shows that delayed lactogenesis was associated with low rate of full breastfeeding and shorter duration of any breastfeeding. Greater efforts to promote breastfeeding should be targeted towards women with delayed lactogenesis.

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH)2D3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5–6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH)2D3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH)2D3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH)2D3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH)2D3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH)2D3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH)2D3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH)2D3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway.

Epidemiological studies have investigated the associations between vitamin D and the risk of adverse pregnancy outcomes; however, the results are conflicting and dose-response relationships remain to be confirmed. This study aimed to summarize previous studies on the associations of vitamin D levels with the risk of gestational diabetes mellitus (GDM), pre-eclampsia (PE), gestational hypertension (GH), and caesarean section (C-section), and to clarify the dose-response trends. PubMed, Embase, Scopus, and Web of Science were searched to identify eligible articles. A total of 69 prospective observational studies including cohort studies, case-cohort studies, or nested case-control studies were included in the current systematic review, of which 68 studies were available for meta-analysis. Compared with the lowest level, the highest level of 25(OH)D was significantly associated with a lower risk of GDM (RR: 0.76; 95% CI: 0.66-0.87), PE (RR: 0.74; 95% CI: 0.60-0.90;), and GH (RR: 0.87; 95% CI: 0.79-0.97); however, no significant relationship was found for C-section (RR: 1.00; 95% CI: 0.90-1.12). There was significant between-study heterogeneity for GDM (I2 = 69.2%; Pheterogeneity < 0.001), PE (I2 = 52.0%; Pheterogeneity = 0.001), and C-section (I2 = 59.1%; Pheterogeneity < 0.001), while no heterogeneity was found for GH (I2 = 0.0%; Pheterogeneity = 0.676). For each 25 nmol L-1 increase in 25(OH)D, the pooled RR was 0.92 (95% CI: 0.86-0.97) for GDM and 0.89 (95% CI: 0.84-0.94) for PE, respectively. Notably, the dose-response analysis showed a non-linear relationship between maternal 25(OH)D levels and the risk of PE (Pnon-linearity = 0.009). Our meta-analysis provides further scientific evidence of the inverse association between 25(OH)D levels and the risk of GDM, PE, and GH, which may be useful for the prevention of pregnancy complications. However, more evidence from prospective studies is needed regarding the dietary intake of vitamin D during pregnancy.

The associations among maternal diet, birth weight, and gestational weight gain are still inconclusive. This study aimed to investigate the associations between maternal dietary patterns and birth weight, and further explore whether GWG mediates these associations. A total of 3,334 pregnant women who completed a validated semi-quantitative food frequency questionnaire from the Tongji Maternal and Child Health Cohort were included. Dietary patterns were extracted by using principal component analysis. Regression models and mediation analyses were performed to explore the associations between dietary patterns and birth weight and the effects of GWG on these associations. Five dietary patterns were identified: “Beans-vegetables,” “Fish-meat-eggs,” “Nuts-whole grains,” “Organ-poultry-seafood” and “Rice-wheat-fruits.” Only women following the “Beans-vegetables” pattern had heavier newborns (β = 47.39; 95% CI: 12.25, 82.54). Women following the “Beans-vegetables” pattern had significantly lower GWG (β = −0.7; 95% CI: −1.15, −0.25) and had a 16% lower risk of excessive GWG and 11% higher odd of adequate GWG. The association between the “Beans-vegetables” pattern and birth weight was negatively mediated by GWG. A dietary pattern enriched in beans and vegetables is beneficial for effectively controlling GWG and increasing birth weight. GWG serves.Clinical Trial Registry: This trial was registered at ClinicalTrials.gov (NCT03099837).

Objective Fresh fruit intake has been found to be associated with risk of gestational diabetes mellitus (GDM); however, the evidence is limited and the findings are inconsistent. We aimed to assess the association of fresh fruit intake by fruit subgroups based on their glycemic index (GI) and glycemic load (GL) values and GDM incidence in Chinese pregnant women. Methods We included 3300 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed by using a validated semiquantitative food frequency questionnaire. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test. In the adjusted logistic regression model, odds ratios and 95% confidence intervals for GDM were computed for the highest compared with lowest quintiles of fruit intake. Results GDM occurred in 378 (11.5%) of 3300 pregnant women. The average fresh fruit consumption was 381.7 g/d. The adjusted odds ratios (95% confidence intervals) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (0.56, 1.12), 0.74 (0.52, 1.05), 0.63 (0.44, 0.92), and 0.41 (0.27, 0.62), respectively; Ptrend Conclusions Our findings suggested an inverse association of fresh fruit intake with the risk of GDM in Chinese pregnant women. In women with GDM risk, low GI and GL fresh fruit consumption should be privileged versus those with high GI and GL.

Background: Maternal diet is critical to the development of gestational diabetes mellitus (GDM), but sparse studies have applied the Chinese Dietary Balance Index for Pregnancy (DBI-P) to assess the maternal dietary quality and its relationship with GDM. We aimed to examine the maternal dietary quality and its relationship with GDM risk using the newly developed DBI-P. Methods: We included 1122 pregnant women from the Tongji Birth Cohort (TJBC) in Wuhan, China. The semi-quantitative food frequency questionnaire (FFQ) was used to obtain the dietary information during pregnancy. The newly developed DBI-P, including DBI-P components and DBI-P dietary patterns, was applied to comprehensively evaluate the maternal dietary quality. GDM was diagnosed by the 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. We used a generalized linear regression model to examine the relationship between DBI-P components and blood glucose levels, and a logistic regression model to examine the relationship between dietary patterns and GDM. Results: A total of 179 participants (16.0%) were diagnosed with GDM. There is a widespread phenomenon of dietary imbalance among pregnant women in Wuhan. With per score increase in nuts and eggs, fasting blood glucose increase by 0.03 mmol/l (95% CI: 0.01, 0.05) and 0.01 mmol/l (95 %CI: 0.01, 0.03), respectively, while per score increase in fruits, 1-h post-load blood glucose decreased by 0.05 mmol/l (95% CI: -0.10, -0.01). Besides, compared with pattern E characterized by higher intake of total energy, total fat, fruits, and cooking oil, pattern B (OR: 0.51, 95% CI: 0.26, 0.99) and pattern C (OR: 0.27, 95% CI: 0.09, 0.81) were associated with a lower GDM risk. The associations between dietary patterns and GDM risk may be partly attributed to the intakes of dietary total fat, carbohydrate, cholesterol, eggs, and cooking oil. Conclusions: Unfavorable dietary quality during pregnancy is associated with a higher risk of GDM. The newly established DBI-P can provide an easy-to-implement tool to assess maternal dietary quality. These findings will provide new insights for the exploration of preferable dietary evaluation methods and prevention and control of GDM.

Background Hypertensive patients, often characterized by chronic inflammation, are susceptible to diabetes. Evidence suggests that the positive association between serum ferritin (SF) and diabetes was affected by high-sensitivity C-reactive protein (hs-CRP), an inflammation marker. We investigate whether there was an interaction between SF and hs-CRP on diabetes in hypertensive patients. Methods We analysed data of 1,735 hypertensive people in this cross-sectional study. Diabetes was diagnosed when fasting blood glucose ≥ 7.0 mmol/L and/or a previous clinical diagnosis of diabetes. Logistic regression models were used to estimate the association of the SF and hs-CRP with diabetes. Multiplicative interaction was evaluated by incorporating a cross-product term for SF and hs-CRP to the logistic regression model. Additive interaction was assessed by calculating the relative excess risk of interaction (RERI) and attributed proportion due to interaction (AP). Results In the adjusted analysis, SF (highest vs lowest tertile: odds ratio [OR], 1.61; 95 % confidence interval [CI], 1.20−2.16) was positively associated with diabetes. There was no multiplicative interaction between SF and hs-CRP, but evidence of additive interaction in regard to diabetes (RERI: 0.86; 95 % CI: 0.06−1.67). Compared to the patients with low SF (lower two thirds) and low hs-CRP (≤ 2 mg/L), those with high SF (upper one third) and high hs-CRP (> 2 mg/L) had increased OR for diabetes (adjusted OR: 2.33 [1.65−3.30]), with 37.0 % of the effects attributed to the additive interaction (AP: 0.37; 95 % CI: 0.09−0.65). Conclusions Within a cross-sectional study consisting of hypertensive patients, co-exposure to high SF and high hs-CRP was synergistically associated with diabetes. Dietary intervention or pharmacological treatment to lowering SF concentration may help to reduce diabetes morbidity in hypertensive patient with chronic inflammation.

The high overall plant-based diet index (PDI) is considered to protect against type 2 diabetes in the general population. However, whether the PDI affects gestational diabetes mellitus (GDM) risk among pregnant women is still unclear. We evaluated the association between PDI and GDM risk based on a Chinese large prospective cohort – the Tongji Maternal and Child Health Cohort. Dietary data were collected at 13–28 weeks of pregnancy by a validated semi-quantitative FFQ. The PDI was obtained by assigning plant food groups positive scores while assigning animal food groups reverse scores. GDM was diagnosed by a 75 g 2-h oral glucose tolerance test at 24–28 weeks of gestation. Logistic regression models were fitted to estimate OR of GDM, with associated 95 % CI, comparing women in different PDI quartiles. Among the total 2099 participants, 169 (8·1 %) were diagnosed with GDM. The PDI ranged from 21·0 to 52·0 with a median of 36·0 (interquartile range (IQR) 33·0–39·0). After adjusting for social-demographic characteristics and lifestyle factors etc., the participants with the highest quartile of PDI were associated with 57 % reduced odds of GDM compared with women in the lowest quartile of PDI (adjusted OR 0·43; 95 % CI 0·24, 0·77; Pfor trend = 0·005). An IQR increment in PDI was associated with 29 % decreased odds of GDM (adjusted OR 0·71; 95 % CI 0·56, 0·90). Findings suggest that adopting a plant-based diet during pregnancy could reduce GDM risk among Chinese women, which may be valuable for dietary counselling during pregnancy.

Background The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. Objectives We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. Methods We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16 weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. Results The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). Conclusions Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Associations between environmental tobacco smoke (ETS) and the risk of adverse birth outcomes may be confounded. We aimed to clarify the associations of ETS before and during pregnancy with the risk of adverse birth outcomes and determine whether the associations were modified by key potential confounders. A total of 7147 non-smoking mothers from the Tongji Maternal and Child Health Cohort (TMCHC) in Wuhan, China, were included in the final analyses. ETS status was self-reported by pregnant women at their first antenatal care visit before 16 gestational weeks. Information on birth outcomes was extracted from delivery records. Poisson regression was used to identify the association between ETS before and during pregnancy and the risk of adverse birth outcomes. Exposures to ETS before and during pregnancy were reported by 645 (9.0%) and 464 (6.5%) mothers, respectively. Compared with no ETS, continued ETS during pregnancy was associated with an increased risk of preterm birth (PTB) (RR: 1.55, 95% CI: 1.07, 2.25) after adjustment for potential confounders. The association remained consistent in medically indicated PTB and late PTB. The risk of PTB associated with continued ETS during pregnancy was significantly increased in mothers more educated (P for interaction < 0.05). However, the increased risk of low birth weight (LBW) or small for gestational age (SGA) births by ETS during pregnancy was not observed. Exposure to ETS during pregnancy was associated with a higher risk of PTB, but not LBW or SGA births in a Chinese birth cohort.

Summary Background Gestational diabetes mellitus (GDM), body mass index (BMI) and gestational weight gain (GWG) are salient predictors of pregnancy-outcomes. However, findings on the association between GDM, BMI, and GWG with fetal growth measures are limited. Objective The aim of this study was to investigate the effect of GDM on fetal growth measures and birth outcomes. Methods All participants came from Tongji Maternal and Child health cohort, in which pregnant women were enrolled before 16 weeks of gestation and had their weights measured regularly during antenatal visits. GDM was diagnosed by oral glucose tolerance test (OGTT) during 24–28 weeks of gestation. Ultrasound measurements of fetal bi-parietal diameters (BPD), head circumferences (HC), abdominal circumferences (AC) and femur length (FL) before birth were collected and neonate outcomes were obtained from the hospital records. Odds ratios were calculated using logistic regression to assess the association of GDM, pre-pregnancy BMI, and GWG with fetal growth measures of ultrasound and birth outcomes, while controlling confounding. Results Of 3253 singleton pregnant women, 293 (9.0%) were diagnosed with GDM, 357 (11.0%) were overweight before pregnancy, and 1995 (61.3%) had excessive GWG. GDM was associated with decreased intrauterine fetal growth measurements including BPD and AC. Maternal pre-pregnancy overweight was associated with increased fetal HC and neonatal birth weight and length, women gained excessive GWG had increased fetal growth measurements of BPD, HC, AC, FL, neonatal birth weight and length. Offspring of GDM women had increased odds of cesarean section 1.31 (1.03, 1.66) and preterm birth 2.02 (1.05, 3.91) in unadjusted models, but these associations disappeared after adjustment. Compared with neonate born to mothers with normal pre-pregnancy weight, those born to underweight mother had higher risk of SGA, and lower risk of cesarean section, LGA and macrosamia, whereas those born to overweight mother had increased risk of cesarean section, LGA and macrosamia. Compared with neonate born to mothers of adequate GWG, neonate of women with excessive GWG had elevated risk of cesarean section, LGA and macrosamia, but lower risk of preterm birth and SGA. Conclusion Pre-pregnancy BMI, GWG and GDM all associated with fetal growth and birth outcomes. The effect of GDM decreased after adjusting pre-pregnancy BMI and GWG. Early screening and management of GDM, preventing excessive GWG could help protect fetuses of GDM mothers from adverse birth outcomes.

We aimed to evaluate the association of the exposure to environmental tobacco smoke (ETS) during pregnancy and infancy with the risk of upper respiratory tract infections (URTI) in infants based on a Chinese birth cohort study. Among 4178 infants who constituted the final study population, 46.8% experienced URTI in their first year of life. The hazard ratios (HR) and 95% confidence intervals (CI) for the risk of URTI were assessed using Cox regression models. Compared with no ETS during pregnancy, continued ETS during pregnancy was independently associated with a higher risk of URTI (HR: 1.36, 95% CI: 1.13, 1.63) after adjustment for potential confounders and also associated with earlier occurrence of URTI (log-rank P = .002). The association remained consistent across the strata defined according to maternal age, number of siblings, sex, and breastfeeding. Exposure to ETS during infancy was associated with URTI only among infants who were breastfed for less than 12 months (P for interaction

Current results regarding the effect of folic acid (FA) supplement use on gestational hypertension (GH) and preeclampsia are limited and inconsistent. We aimed to investigate whether FA supplement use was associated with GH and preeclampsia. Participants from the Tongji Maternal and Child Health Cohort with information on periconceptional FA supplement use and diagnosis of GH/preeclampsia were included (n=4853). Robust Poisson regression was used to assess the association of FA supplement use and GH and preeclampsia. Among the 4853 participants in this study, 1161 (23.9%) and 161 (3.3%) women were diagnosed with GH and preeclampsia, respectively. The risk ratio of developing GH was higher in women who used ≥800 µg/d FA supplement from prepregnancy through midpregnancy than nonusers (risk ratio, 1.33 [1.08–1.65]). After adjusting for social-demographic, reproductive, lifestyle factors, family history of hypertension, other supplement use, and gestational weight gain, the adverse association remained significant (risk ratio, 1.32 [1.06–1.64]). Restricting the analysis among women with normal weight, without family history of hypertension, and without gestational diabetes mellitus, the positive FA-GH association still existed. We did not find any significant association between FA supplement use and preeclampsia regardless of adjustment. High-dose (≥800 µg/d) FA supplement use from prepregnancy through midpregnancy was associated with increased risk of GH. Attention should be given to avoid the potential risk of GH due to inappropriate FA supplement use in women who are planning or capable of pregnancy.

Vitamin D deficiency has been reported to be associated with respiratory tract infection (RTI). However, evidence regarding the effects of vitamin D supplementation on susceptibility of infants to RTI is limited. In this prospective birth cohort study, we examined whether vitamin D supplementation reduced RTI risk in 2,244 infants completing the follow‐up from birth to 6 months of age. The outcome endpoint was the first episode of paediatrician‐diagnosed RTI or 6 months of age when no RTI event occurred. Infants receiving vitamin D supplements at a daily dose of 400–600 IU from birth to the outcome endpoint were defined as vitamin D supplementation and divided into four groups according to the average frequency of supplementation: 0, 1–2, 3–4, and 5–7 days/week. We evaluated the relationship between vitamin D supplementation and time to the first episode of RTI with Kaplan–Meier plots. The associations of vitamin D supplementation with infant RTI, lower RTI (LRTI), and RTI‐related hospitalization were assessed using modified Poisson regression. The median time to first RTI episode was 60 days after birth (95% CI [60, 90]) for infants without supplementation and longer than 6 months of age for infants with supplementation (p < .001). We observed inverse trends between supplementation frequency and risk of RTI, LRTI, and RTI‐related hospitalization (p for trend < .001), with the risk ratios in the 5–7 days/week supplementation group of 0.46 (95% CI [0.41, 0.50]), 0.17 (95% CI [0.13, 0.24]), and 0.18 (95% CI [0.12, 0.27]), respectively. These associations were significant and consistent in a subgroup analysis stratified by infant feeding.

Background: A growing number of epidemiologic studies have estimated associations between type 2 diabetes mellitus and exposure to metals. However, studies on the associations of internal assessments of metal exposure and gestational diabetes mellitus (GDM) are limited in scope and have inconsistent outcomes. Objectives: This investigation aimed to explore the associations between urinary nickel (Ni), arsenic (As), cadmium (Cd), antimony (Sb), cobalt (Co), or vanadium (V) in early pregnancy and the subsequent risk of GDM in Chinese pregnant women. Methods: The study population included 2090 women with singleton pregnancy from the Tongji Maternal and Child Health Cohort (TMCHC). Urine samples were collected before 20 gestational weeks, and an oral glucose tolerance test (OGTT) was conducted at 24–28 gestational weeks to diagnose GDM. The concentrations of urinary metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) and were corrected for urinary creatinine. The associations between the risk of GDM and urinary metals were assessed using Poisson regression with a robust error variance with generalized estimating equations (GEE) models and Bayesian kernel machine regression (BKMR). Results: A total of 241 participants (11.53%) were diagnosed with GDM. Five metals (Ni, As, Sb, Co, and V) were found significantly and positively associated with GDM based on single-metal models. In multiple-metal models, for each unit increase of ln-transformed urinary Ni or Sb, the risk of GDM increased 18% [relative risk (RR):1.18, 95%confidence interval (CI): 1.00, 1.38 or RR: 1.18, 95%CI: 1.00, 1.39, respectively]. The BKMR analysis revealed a statistically significant and positive joint effect of the six metals on the risk of GDM, when the urinary levels of the six metals were all above the 55th percentile, compared to the median levels. The effect of metal Ni was significant when the concentrations of the other metals were all fixed at their 25th percentile, and metal Sb displayed a significant and positive effect when all the other metals were fixed at 25th, 50th, and 75th percentiles. Conclusions: To the best of our knowledge, this study is the first to demonstrate that increased concentrations of urinary Ni in early pregnancy are associated with an elevated risk of GDM, either evaluated individually or as a metal mixture. All six metals mixed exposure was positively associated with the risk of GDM, while Sb and Ni were demonstrated more important effects than the other four metals in the mixture. Keywords: GDM, Urinary metals, Single-metal models, Multiple-metal models, BKMR models

Background The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity. Methods This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses. Discussion Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases. Trial registration Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.

Background Maternal iodine status has been suggested to affect birth outcomes. Few studies have focused on its effects on fetal growth during pregnancy. Objective This study aimed to assess maternal iodine status during early pregnancy and further examine the relation between maternal iodine status and fetal growth. Methods A total of 2087 singleton-pregnant women participating in the Tongji Maternal and Child Health Cohort study were involved. Urinary iodine concentration (UIC) and creatinine concentration were measured in spot urine samples collected in early pregnancy (

Breastfeeding is of great benefit to infants and their mothers. Caesarean delivery (CD) have increased worldwide in recent years and emerging evidence has implied that CD may influence the initiation and duration of breastfeeding. However, the findings are inconsistent and intricate. The aim of this study is to illuminate the association between the CD and the initiation and duration of breastfeeding in the first 6 months postpartum. A total of 2058 mother–infant pairs were studied in this prospective study. Delivery information was obtained from birth records. Feeding information in the first 6 months postpartum were collected from face-to-face interviews. Logistic regression was used to explore the association between CD and the initiation and duration of breastfeeding. After adjustment for potential confounders, CD was significantly associated with the unsuccessful initiation of breastfeeding [odds ratio (OR): 1.943, 95% confidence interval (CI): 1.050–3.597] and delayed initiation of breastfeeding [OR: 1.450, (95% CI: 1.041–2.019)], when compared with vaginal delivery (VD). More importantly, for mothers who had initiated breastfeeding, CD was associated with significantly higher risks of an inability to sustain full breastfeeding (OR: 1.369, 95% CI: 1.128–1.662), any breastfeeding at 3 months postpartum (OR: 1.715, 95% CI: 1.265–2.325) and any breastfeeding at 6-month postpartum (OR: 1.462, 95% CI: 1.174–1.820). CD is an independent risk factor for the inability to initiate and sustain breastfeeding. It is desirable to reduce the CD rate and provide specific breastfeeding support during early postpartum period to CD mothers.

Objective Information is limited regarding the possible relationship between diet-related inflammation and the risk of gestational diabetes mellitus (GDM). This study investigated the association between the inflammatory potential of the diet, measured by the dietary inflammatory index (DII), and GDM risk in pregnant Chinese women. Methods This study included 2639 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intake was assessed by a validated semiquantitative food frequency questionnaire and was used to calculate the DII score. The DII was then validated using C-reactive protein measurements in a subsample of 133 pregnant women. GDM diagnoses were collected from medical records based on the results of a 75 g oral glucose tolerance test at 24 to 28 wk gestation. Multivariable-adjusted logistic regression models were performed to estimate the odds ratios (ORs) for GDM risk by DII score, modeled continuously and in tertiles. Results Of the 2639 participants, 13.1% were diagnosed with GDM. DII scores ranged from –4.45 to 3.15 and were positively associated with C-reactive protein (adjusted β : 1.28, 95% confidence interval [CI]: 0.16, 2.40; P trend = 0.023) when comparing DII tertile 3 (most pro-inflammatory) to tertile 1 (most anti-inflammatory). A significant and positive association was observed between DII scores and GDM risk (adjusted OR: 1.43; 95% CI: 1.05, 1.95; P trend = 0.022) comparing the highest versus lowest tertiles. The stratified analysis showed that this association was stronger in pregnant women who were overweight or obese before pregnancy (adjusted OR: 2.20; 95% CI: 1.03, 4.69). Conclusions These findings suggest that a higher DII score, corresponding to a more proinflammatory diet, is associated with a higher risk of GDM, particularly in pregnant women who were overweight or obese before pregnancy.

Objectives To examine the relationship between prenatal nitrogen dioxide (NO 2 ) exposure and foetal growth in a prospective cohort of 1001 Chinese women. Methods The maternal NO 2 exposure levels were estimated using land-use regression models based on home address. The biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated foetal weight (EFW) were evaluated via ultrasonography. The multiple linear regression model was used to adjust for confounders, and the mixed-effect model was used to assess longitudinal effect. Results With a 10 μg/m 3 increase in NO 2 exposure, the BPD, HC, AC, FL and EFW in the second trimester decreased by 0.40 mm (95% CI −0.56 to −0.24), 1.07 mm (95% CI −1.60 to −0.54), 1.02 mm (95% CI −1.57 to −0.48), 0.24 mm (95% CI −0.37 to −0.12) and 7.84 g (95% CI −11.59 to −4.08), respectively; the BPD and HC in the third trimester decreased by 0.26 mm (95% CI −0.50 to −0.02) and 0.71 mm (95% CI −1.37 to −0.06), respectively. The longitudinal analyses showed inverse associations of NO 2 exposure with BPD, HC, AC and FL (all p 2 on the HC, FL and EFW in the second trimester were stronger among female babies and that the effect of NO 2 on EFW in the third trimester was stronger among smoking mothers (all p Conclusions In this prospective study of Chinese women, maternal NO 2 exposure was inversely associated with foetal growth, and the association was stronger among female babies and smoking mothers.

To assess the longitudinal associations between maternal total bile acid (TBA) levels during early mid-pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). In a prospective cohort study, pregnant women who were enrolled prior to gestational week 16 were followed until delivery. TBA levels were tested during weeks 14–18 of gestation. Using logistic regression, we analyzed the associations between quartiles of TBA and GDM based on a 75-g oral glucose tolerance test (OGTT) at 24–28 gestational weeks. The GDM rate was 7.9% (114/1441). The mean TBA level was higher in women with GDM than in those without GDM (2.1 ± 2.0 vs 1.5 ± 1.0 µmol/L, P = 0.000). The highest TBA level quartile (2.1–10.7 µmol/L) had a 1.78-fold (95% CI 1.01, 3.14) increased risk of GDM compared with that of the lowest quartile (0.0–0.8 µmol/L) after adjusting for pre-pregnancy body mass index (BMI), gestational, age at TBA test and other confounders. High TBA levels were involved in the fasting glucose level rather than that at 1 h and 2 h after OGTT in all participants. Pregnant women with higher serum TBA levels during early mid-pregnancy have a higher risk of developing GDM. TBA may be a new risk factor for GDM.

Environmental chemical exposures have been implicated as risk factors for the development of non-alcoholic fatty liver (NAFLD). Bisphenol S (BPS), widely used in multitudinous consumer products, could disrupt lipid metabolism in the liver. This study aimed at examining the hypothesis that long-term exposure to BPS promotes the development of liver fibrosis and inflammation by means of the application of a semi-static exposure experiment that exposed zebrafish to 1, 10, and 100 μg/L BPS from 3 h post fertilization to 120 day post fertilization. Results showed that the 120-d BPS exposure elevated plasma aspartate aminotransferase and alanine aminotransferase activities, increased triacylglycerol (TAG) and total cholesterol levels in male liver, and even induced hepatic apoptosis and fibrosis. Hepatic lipid accumulation observed in the 30-d BPS-exposed zebrafish was recovered after a 90-d depuration phase, thereby indicating that long-term BPS exposure promotes the progression of simple steatosis to non-alcoholic steatohepatitis. Furthermore, BPS exposure for 120-d promoted the synthesis of TAG and lipotoxic free fatty acids by elevating the transcription of srebp1, acc, fasn, and elovl6, induced endoplasmic reticulum (ER) stress with increasing expression levels of unfolded protein response (UPR) genes (perk, hsp5, atf4a, and ddit3), and then stimulated the expression of two key autophagy genes (atg3 and lc3) and inflammatory genes (il1b and tnfα). It is indicated that BPS can induce the development of steatohepatitis via the activation of the PERK-ATF4a pathway of the UPR. Data gathered suggest that environmental pollutants-induced ER stress with the activation of UPR can potentially trigger the NAFLD development in males. Overall, our study provided new sights into understanding of the adverse health effects of metabolism disrupting chemicals.

We aimed to assess protein nutrition status during pregnancy by maternal plasma total protein (MTP) levels in urban pregnant women and to explore the association between the trimester‐specific MTP levels and risk of preterm birth (PTB). A prospective design was conducted in 3,382 mother‐newborn pairs with the second‐trimester maternal MTP information and in 3,478 mother‐newborn pairs with the third‐trimester MTP information. Multiple Cox proportional hazard regression and multiple linear regression were used to analyse the associations between MTP levels and PTB risk as well as gestational duration, respectively. Nearly all the second‐trimester MTP levels were within the clinical reference range, but more than 40% of the third‐trimester MTP levels were less than the lower limit of normal. No significant association was found between the second‐trimester MTP level and PTB risk. However, the adjusted hazard ratios (HRs) of PTB across increasing quartiles of the third‐trimester MTP levels were 1.00 (reference), 0.59 (0.36, 0.95), 0.35 (0.20, 0.60), and 0.32 (0.19, 0.53) (p for trend < 0.001), respectively. Each standard deviations increment of the third‐trimester MTP was associated with increase of 0.13 weeks in gestational duration. Moreover, stratified analyses showed that the effects of third‐trimester MTP on PTB risk and gestational duration were stronger in pregnant women carrying female offspring than those carrying male offspring (p for interaction < 0.05). The third‐trimester MTP level was inversely associated with PTB risk and was positively associated with gestational duration. Improving third‐trimester MTP level may be helpful for preventing PTB.

OBJECTIVES: Studies investigating association between manganese (Mn) and type 2 diabetes (T2D) were controverial and relationship between Mn and gestational diabetes mellitus (GDM) remains unclear. We aimed to explore the association between urinary Mn levels and GDM. METHODS: The study population included 2093 singleton pregnant women from Tongji Maternal and Child Health Cohort (TMCHC), a prospective cohort study in China. The maternal urine specimens were collected before 20 weeks of gestation and determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Odds ratios (ORs) for GDM were compared according to urinary Mn levels in quartiles using logistic regression after adjusting for potential covariates. Stratified analyses and interactive analyses were conducted. Then restricted cubic spline (RCS) regression was applied. Association between urinary Mn levels and glucose levels was assessed by linear regression. RESULTS: The medians (interquartile range) (IQR) of urinary gestation and Mn levels were 13.2 (12.2, 15.8) weeks and 0.8 (0.4–1.4) μg/g creatinine (Cr), respectively. A total of 241 (11.5%) participants were diagnosed with GDM. The odds ratios (ORs) and 95% confidence intervals (CIs) of GDM were 1.76 (1.15, 2.71) for the third quartile of urinary Mn levels and 2.00 (1.29, 3.10) for the highest quartile compared with the lowest quartile after adjustment. The adverse effect remained in all the subgroups stratified by age, primigravida, pre-pregnancy BMI, fetal sex, family history of diabetes, BMI at OGTT and physical activity. In RCS, the adverse association was consistently showed. Higher urinary Mn levels were found to be associated with higher fasting blood glucose (FBG) (P(trend )= 0.002) but not post-prandial. CONCLUSIONS: Our findings suggested a positive association between urinary Mn levels and GDM. FUNDING SOURCES: This study is supported by the National Program on Basic Research Project of China and the Fundamental Research Funds for the Central Universities. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

OBJECTIVES: To explore whether lutein could activate Sirtuin 1 and up-regulate hormone-sensitive lipase (ATGL) and adipose triglyceride lipase (HSL) and then further improve lipid metabolism in liver and abdominal tissues. METHODS: Animals were randomly divided into two groups after acclimation for 5 d. One group was fed a normal diet (ND) (n = 20), while the other group was fed a high fat diet (HFD) (n = 20) for 12 d to induce lipid metabolism disturbance. Based on total cholesterol, the rats fed the ND or HFD were then divided into 2 groups respectively, including four groups: ND, ND + LUT, HFD, HFD + LUT, administered by 25 mg/kg·bw/day lutein for the next 5 weeks. At the end of experiment, all rats were euthanized. RESULTS: (1) Lutein supplementation significantly decreased the body weight (P

Investigators in previous studies have drawn inconsistent conclusions regarding the relationship between relatively low exposure to fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5)) and risk of gestational diabetes mellitus (GDM), while the association between high PM2.5 exposure and GDM risk has not been well studied. We investigated the association of high PM2.5 exposure during pregnancy with blood glucose levels and GDM risk in Chinese women. The present study was conducted from August 2013 to May 2016 among 3,967 pregnant women in the Tongji Maternal and Child Health Cohort in Wuhan, China. PM2.5 exposure during pregnancy for each participant was estimated by means of land-use regression models. An interquartile-range increase in PM2.5 exposure (33.84 μg/m3 for trimester 1 and 33.23 μg/m3 for trimester 2) was associated with 36% (95% confidence interval (CI): 1.15, 1.61) and 23% (95% CI: 1.01, 1.50) increased odds of GDM during trimester 1 and trimester 2, respectively. An interquartile-range increment of PM2.5 exposure during trimester 1 increased 1-hour and 2-hour blood glucose levels by 1.40% (95% CI: 0.42, 2.37) and 1.82% (95% CI: 0.98, 2.66), respectively. The same increment of PM2.5 exposure during trimester 2 increased fasting glucose level by 0.85% (95% CI: 0.41, 1.29). Our findings suggest that high PM2.5 exposure during pregnancy increases blood glucose levels and GDM risk in Chinese women.

Aims Iron supplementation has been recommended for healthy pregnancy, but concerns have been raised regarding the potential adverse effects. We sought to examine the impact of periconceptional iron supplement use on subsequent gestational diabetes mellitus (GDM) risk. Methods Participants (N = 5101) with information on periconceptional micronutrient supplementation and diagnosis of GDM were involved. Information on iron supplementation and general characteristics were collected at enrollment and follow-up visits. GDM was diagnosed by oral glucose tolerance tests (OGTT) conducted at 24–28 weeks of gestation. Robust Poisson regression model was used to estimate the relative risks (RRs) and 95% confidence intervals (CI) for the effect of iron supplement use on GDM. Results 10.5% of the participants were diagnosed with GDM and the incidence was significantly higher in users with iron >30 mg/d for more than 3 months (Iron >30-L) than in nonusers. Adjusted RRs (95% CI) were 1.53 (1.21, 1.93) in Iron >30-L group, 1.14 (0.80, 1.61) in users with iron >30 mg/d for 30-S) and 1.15 (0.86, 1.54) in users with iron ≤30 mg/d for any duration (Iron ≤30) respectively, compared to nonusers. This link in Iron >30-L group was even stronger (adjusted RR: 1.70, 95% CI: 1.25, 2.31) when restricting the analysis among primiparous and iron-replete participants without family history of diabetes. There were no significant differences in birth outcomes among groups. Conclusions Periconceptional iron supplementation >30 mg/d for long-term was associated with increased GDM risk. The need and safety of prophylactic iron supplement in iron-replete pregnant women should be reconsidered.

OBJECTIVES: Concerns relative to excessive iron intake are raised when high iron status exposure has been linked in observational studies to a greater risk of gestational diabetes mellitus (GDM). We aimed to examine the association between iron intake during pregnancy and GDM risk in Chinese women. METHODS: The study included 2174 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC), a prospective cohort in Wuhan, China. Iron intakes from food and supplementation prior to GDM diagnosis were assessed using a validated food frequency questionnaire (FFQ) and a detailed supplement questionnaire collected at 13–28 weeks of gestation. GDM was ascertained by an oral glucose tolerance test at 24–28 weeks of gestation. Odd ratios (ORs) of GDM in relation to categories of iron intake (i.e., quartiles of total and food iron intake, categories of supplemental iron intake [0, 0–30, >30 mg/day]) were estimated using logistic regression models, with adjustment for demographic, dietary and lifestyle factors. RESULTS: A total of 242 (11.1%) women were diagnosed with GDM. The adjusted ORs (95% CIs) for the risk of GDM associated with the higher quartiles compared with the lowest quartile of total iron intake were 1.44 (0.89, 2.33), 2.03 (1.27, 3.25), and 2.86 (1.84, 4.43), respectively (P for trend 30 mg/day during pregnancy had an OR for GDM of 2.32 (95% CI: 1.60, 3.36). Moreover, the significant positive effect of supplemental iron was mainly attributed to iron supplementation during mid-pregnancy (≥60 vs. 0 mg/day, OR: 1.46, 95% CI: 1.00, 2.13), while no effect of iron supplementation during early pregnancy was observed. No significant association was found between food iron intake and GDM. CONCLUSIONS: Higher supplemental iron intake during pregnancy was significantly associated with elevated GDM risk. Adverse effect of indiscriminate iron supplementation, especially inappropriate supplementation during mid-pregnancy, would likely outweigh benefits for maternal health. FUNDING SOURCES: Funding was received from the National Natural Science Foundation of China (NSFC81673159), National Program on Basic Research Project of China (NO.2013FY114200) and the Fundamental Research Funds for the Central Universities (HUST 2019kfyXMPY008) (Nianhong.Yang.).

Objective Obesity is now a worldwide disease and is mainly attributable to increased body fat deposition. In a growing number of epidemiological studies, lutein has been revealed to have different degrees of anti-obesity properties, but the potential underlying mechanisms that have been reported are limited. Therefore, we aimed to clarify the protective effects of lutein against excessive lipid accumulation, and we explored the role of SIRT1 and SIRT1-mediated pathways both in abdominal adipose tissue and mature 3T3-L1 cells during lutein administration. Methods In our design, male Sprague–Dawley rats were fed either control or high-fat diets with or without 25 mg/kg·bw/day lutein for 5 weeks. Additionally, differentiated 3T3-L1 cells were incubated with 40 μM lutein or 10 μM Ex527 for 24 h. Results Lutein supplementation decreased the body weight, abdominal fat index ratio, frequency and mean area of larger adipocytes in HE staining induced by the high-fat diet and then activated the expression of SIRT1 and thus upregulated FoxO1, ATGL, and HSL expression and downregulated SREBP-1, FAS, and ACC expression both in abdominal adipose tissue and differentiated 3T3-L1 cells. However, coincubation with Ex527 and lutein suppressed the activation of SIRT1 and reversed the expression of FoxO1, ATGL, HSL, SREBP-1, FAS, and ACC in comparison to those in the Lut group. Conclusions Overall, we suggest that the effects of lutein on attenuating excessive lipid accumulation are dependent on the SIRT1-mediated pathway in vivo and in vitro, which indicates that lutein administration may be a potential strategy for preventing excessive lipid accumulation and obesity.

Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.

OBJECTIVES: The overall plant-based diet index (PDI) has been demonstrated to be protective against type 2 diabetes (T2D) in the general population. Whether the PDI was linked to gestational diabetes mellitus (GDM) is unclear. We aimed to assess the association of the PDI with GDM incidence in Chinese pregnant women. METHODS: A total of 2099 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) were included in the present study. Dietary data were collected at 13–28 wks of pregnancy by using a validated semi-quantitative food frequency questionnaire (FFQ). Food groups including cereals, fruits, vegetables, nuts, beans, vegetable oil, dairy, eggs, meat, and fish, were ranked into quintiles and given positive (1–5 for plant food groups) or reverse (5–1 for animal food groups) scores. The PDI was obtained by summing the 10 food group scores, with a theoretical range of 10 to 50. GDM was diagnosed by the 75-g 2-h oral glucose tolerance test at 24–28 wks. Cubic-restricted spline function and logistic regression analyses were used to examine the association between the PDI during pregnancy and GDM. RESULTS: GDM was reported by 8.1% of the 2099 pregnancies. The PDI score ranged from 17 to 43 (theoretical range: 10–50), the mean (SD) was 30.2 (4.4). After adjusting for maternal age, ethnicity, education, income, parity, gravidity, family history of diabetes, total energy intake per day, and other pre-pregnancy information such as body mass index (BMI), smoking status, drinking status, exercise, and sleep quality, a linear association between the PDI and GDM risk was demonstrated by the restricted cubic splines (P for overall association = 0.024, P for nonlinearity = 0.370). Compared to the lowest quartile 1 of PDI, ORs (95% CI) were 0.91 (0.59, 1.42) for quartile 2, 0.91 (0.58, 1.41) for quartile 3, and 0.52 (0.30, 0.89) for quartiles 4 (P for trend = 0.040) in the adjusted model. CONCLUSIONS: Our study suggests that higher PDI is associated with a substantially lower risk of developing GDM, which indicates that adopt plant-based diets during pregnancy could be an easy avenue to reduce GDM risk. FUNDING SOURCES: Funding was received from the National Program on Basic Research Project of China (NO.2013FY114200) and the Fundamental Research Funds for the Central Universities (HUST2016YXZD040) for Nianhong Yang.

SIRT1 has been proposed to enhance insulin secretion in β-cell through repressing the expression of uncoupling protein2 (UCP2), but whether ethanol-induced β-cell dysfunction is mediated by the disrupted SIRT1-UCP2 axis remains unknown. This study was conducted to explore the underlying mechanisms by which ethanol resulted in β-cell dysfunction and the potential protective effects of resveratrol in this process. INS-1 cells (rat pancreatic β-cell line) were cultured with ethanol in the presence or absence of resveratrol (2.5, 12.5 μmol/L). The results showed that ethanol exposure reduced glucose-stimulated insulin secretion, ATP production and SIRT1 expression but increased UCP2 expression, while supplementation with resveratrol restored the function of INS-1 cell by upregulating SIRT1 and inhibiting UCP2. Moreover, the critical role of SIRT1-UCP2 axis was further supported by the results that SIRT1 activator SRT1720 reversed ethanol-induced impairment of glucose-stimulated insulin secretion by decreasing UCP2, while SIRT1 inhibitor Ex527 abolished the beneficial effects of resveratrol. Meanwhile, NAD+ booster nicotinamide mononucleotide also counteracted the deleterious effects of ethanol by increasing SIRT1, suggesting the regulation of SIRT1-UCP2 axis may be associated with cellular NAD+/NADH ratio. In conclusion, our observations imply that ethanol induces impaired insulin secretion from INS-1 cell through disrupting SIRT1-UCP2 axis, while resveratrol may reverse this process by augmenting SIRT1 and inhibiting UCP2.

Periconceptional folic acid (FA) supplementation is widely recommended for substantial benefits on preventing neural tube defects (1), but concerns regarding the potential side effects on both mothers and their infants have been raised recently (2,3). Higher plasma folate was found to be associated with higher risk of gestational diabetes mellitus (GDM) (4). A Chinese cohort had reported association between FA supplement use in early pregnancy and increased GDM risk (5). However, no details on FA doses and durations had been addressed. To further understand the safe dose and duration of FA supplement use regarding GDM risk, for the first time, we evaluated the impact of FA supplement use on GDM with consideration of both doses and durations. Participants came from the Tongji Maternal and Child Health Cohort (TMCHC), a cohort investigating the role of maternal nutritional, environmental, and lifestyle influences on the outcomes of pregnant women and their offspring. Information on social-demographic status, reproductive factors, lifestyle factors, illnesses, and medical records was collected via questionnaire-based interviews at enrollment (

Emerging clinical evidence has implied that alkaline phosphatase (ALP) may contribute to gestational diabetes mellitus (GDM). However, there were no studies to reveal the independent and prospective associations between ALP and GDM. Our aim was to explore the independent and prospective associations between early maternal ALP level and GDM risk and glucose regulation. In a prospective cohort study with 2073 singleton mothers at four maternity units in China, maternal serum ALP levels were measured before 20 gestational weeks. Using logistic regression, we analyzed the relationship between maternal ALP level and risk of GDM. We further explored the relationships of ALP level to fasting blood glucose (FBG), 1-h and 2-h post-load blood glucose (1-h, 2-h PBG) with multiple linear regression. Finally, we analyzed the association between maternal ALP level and isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT) risk. The maximum value of maternal ALP level was 90 U/L, within the normal range. After adjustment for confounding factors, the odds ratio (ORs) of GDM increased linearly with ALP level (p for overall association = 0.002, p for nonlinear association = 0.799), with the OR comparing the highest versus lowest quartile of 2.47 (95% CI 1.47, 4.15). Moreover, each additional of 10 U/L ALP level was associated with a 2% higher FBG (p = 0.043) and a 12% higher 1-h PBG (p = 0.004). Higher ALP level also increased the risk of i-IFG (OR 3.73, 95% CI 1.17–11.86) and i-IGT (OR 2.03, 95% CI 1.07–3.84). Even within the upper limit of normal, higher early maternal ALP level could increase the risk of GDM. Moreover, both FBG and PBG were increased with early maternal ALP.

Background: Antimony (Sb) has been associated with type 2 diabetes in previous studies. However, the role of Sb in the incidence of Gestational diabetes mellitus (GDM) remains unclear. Objectives: We investigated the association between Sb exposure during early pregnancy and the risk of GDM. Methods: We performed a prospective study of 2093 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC). Sb concentrations were measured in urine samples during early pregnancy by ICP-MS. The association between urinary Sb concentration and GDM incidence was assessed using robust Poisson regression model after adjustment for confounders. Results: The 95th percentile value of creatinine-corrected Sb (CC-Sb) concentration in the urine of all pregnant women was 1.33 μg/g. The CC-Sb concentrations were significantly higher in women with GDM than those without GDM (median value: 0.49 μg/g vs. 0.38 μg/g, p = 0.001). After adjustment for potential confounders, for each one natural logarithmic unit increase in Sb concentration, there was 29% [adjusted relative risk (RR) = 1.29; 95% confidence interval (CI): 1.06, 1.57] increase in the risk of GDM. Women in the highest tertile for CC-Sb had a 1.92-fold (95% CI: 1.42, 2.60) higher risk of GDM compared with women in the lowest tertile (p-value for trend

Summary Background & aims Oxidative stress has been implicated in the pathogenesis of gestational diabetes mellitus (GDM). Vitamin C as natural antioxidant may help to increase the body's antioxidant capacity. The study is aimed to determine whether vitamin C intake during pregnancy is associated with lower risk of GDM. Methods Women with singleton pregnancy and without any history of diabetes were drawn from the ongoing Tongji Maternal and Child Health Cohort (TMCHC). Oral glucose tolerance tests (OGTT) were conducted during weeks 24–28 of gestation to screen for GDM. A validated food frequency questionnaire (FFQ) was used to assess dietary intake during mid pregnancy. Use of multivitamins and specific supplements of vitamin C was assessed by questionnaires. Odds ratios (ORs) of GDM risk were calculated by logistic regression models, adjusted for potential confounders. Results 344 (11.4%) of the 3009 women were diagnosed with GDM. Dietary vitamin C intake was inversely associated with the risk of GDM. Women with above adequate dietary vitamin C intake (more than 200 mg/day) experienced lower odds of GDM (OR 0.68, 95% CI: 0.49–0.95) than those with adequate intake (115–200 mg/day). There was no association between the total consumption of vitamin C and the risk of GDM (OR 1.04, 95% CI: 0.71–1.53). Conclusion This data suggests that higher dietary consumption of vitamin C during pregnancy is independently associated with lower odds of GDM. Above 200 mg/day of dietary vitamin C intake may help reduce the odds of GDM. However, no such association between total vitamin C intake and the risk of GDM was found. Hence, sufficient vegetables and fruits rich in vitamin C should be recommended to protect pregnant women from developing gestational diabetes.

Summary Background & aims Delayed onset of lactogenesis II (OL) negatively affects breastfeeding and consequently, the health of the newborn. Few studies have examined the association between gestational weight gain (GWG) throughout pregnancy and risk of delayed OL. Methods We used data from a prospective cohort study in Wuhan of China, which enrolled pregnant women at 8–16 weeks of gestation and followed-up regularly. GWG was assessed by the last available weight measurement (LAWM) during pregnancy and the self-reported pre-pregnancy weight at enrollment. The outcome was delayed OL self-reported after 4 days postpartum. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression. Results Delayed OL was reported by 18.4% of the 3282 participants. After adjustment for the demographic, clinical and breastfeeding characteristics, compared to the lowest quartile 1 of GWG, ORs (95% CIs) were 1.20 (0.91, 1.57) for quartile 2, 1.47 (1.13, 1.92) for quartile 3, and 1.42 (1.08, 1.86) for quartile 4 (P for trend = 0.006). When GWG was classified by the 2009 Institute of Medicine (IOM) guidelines, compared with women with adequate GWG, the adjusted ORs (95% CIs) were 0.82 (0.61, 1.10) for inadequate GWG, and 1.13 (0.93, 1.38) for excessive GWG. Conclusions Women with higher GWG throughout pregnancy are more likely to suffer from delayed OL in Chinese population.

Aims It is evident that adverse childhood experiences (ACEs) can influence health status of adult life, but few large-scale studies have assessed the relation of ACEs with type 2 diabetes. This meta-analysis aimed to summarize existing evidence on the link between ACEs and type 2 diabetes in adults. Materials and method We searched all published studies from PubMed and EMBASE before Aug 2015 using keywords like adverse childhood experiences and diabetes, and scanned references of relevant original articles. We included studies that reported risk estimates for diabetes by ACEs and matched our inclusion criteria. We examined the overall relationship between ACEs and diabetes, and stratified the analyses by type of childhood adversities, study design and outcome measures, respectively. Results Seven articles fulfilled the inclusion criteria for this Meta-analysis, comprising 4 cohort and 3 cross-section studies. A total of 87,251 participants and 5879 incident cases of type 2 diabetes were reported in these studies. The exposure of ACEs was positively associated with the risk of diabetes with a combined odds ratio of 1.32 (95% confidence interval 1.16 to 1.51) in the total participants. The influence of neglect was most prominent (pooled odds ratio 1.92, 95% confidence interval 1.43 to 2.57) while the effect of physical abuse was least strong (pooled odds ratio 1.30, 95% confidence interval 1.19 to 1.42). The pooled odds ratio associated with sexual abuse was 1.39 with the 95% confidence intervals from 1.28 to 1.52. Conclusions The results support a significant association of adverse childhood experiences with an elevated risk of type 2 diabetes in adulthood.

Objectives To examine the relationship between poor sleep quality during pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A total of 4066 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed. Sleep quality and duration during early pregnancy were self-reported by enrolled women at their first antenatal care visit before 16 weeks of gestation. Gestational diabetes mellitus (GDM) was assessed with a 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Information about self-reported sleep quality and duration in mid-pregnancy were also collected at this time. Odds ratios (OR) and 95% CIs were calculated by multivariable logistic regression models, and adjusted for potential confounders to estimate the effect of poor sleep quality and the interaction between sleep quality and duration on the development of GDM. Stratified analyses were performed according to age, parity, family history of diabetes and napping. Results A total of 335 (8.2%) participants were diagnosed with GDM. Poor sleep quality was reported in 259 (6.4%) women during early pregnancy and 248 (6.1%) in mid-pregnancy. The risk of GDM was increased in women with poor sleep quality during early pregnancy (OR 1.77, 95% CI 1.20–2.61). No association was found between poor sleep quality during mid-pregnancy and the risk of GDM. The risk of GDM was highest in women with poor sleep and longer nighttime sleep duration during early pregnancy (OR 2.27, 95% CI 1.20–4.29) when compared with those who reported good sleep and 7.0–8.5 h of sleep duration per night. Stratified analysis found that the association between poor sleep quality in early pregnancy and the risk of GDM was stronger among women aged ≥30 years (OR 2.35, 95% CI 1.35–4.09) and those with a family history of diabetes (OR 4.02, 95% CI 1.54–10.48). Conclusions Poor sleep quality during early pregnancy was associated with an increased risk of GDM. Screening for and treating sleep problems in early pregnancy could potentially reduce the risk of GDM.

The available findings concerning the association between branched-chain amino acids (BCAAs)—particularly leucine—and insulin resistance are conflicting. BCAAs have been proposed to elicit different or even opposite effects, depending on the prevalence of catabolic and anabolic states. We tested the hypothesis that leucine supplementation may exert different effects at different stages of insulin resistance, to provide mechanistic insights into the role of leucine in the progression of insulin resistance. Male Sprague-Dawley rats were fed a normal chow diet, high-fat diet (HFD), HFD supplemented with 1.5% leucine, or HFD with a 20% calorie restriction for 24 or 32 weeks. Leucine supplementation led to abnormal catabolism of BCAA and the incompletely oxidized lipid species that contributed to mitochondrial dysfunction in skeletal muscle in HFD-fed rats in the early stage of insulin resistance (24 weeks). However, leucine supplementation induced no remarkable alternations in BCAA catabolism, but did enhance mitochondrial biogenesis with a concomitant improvement in lipid oxidation and mitochondrial function during the hyperglycaemia stage (32 weeks). These findings suggest that leucine trigger different effects on metabolic signatures at different stages of insulin resistance, and the overall metabolic status of the organisms should be carefully considered to potentiate the benefits of leucine.

Summary Background & aims Gestational diabetes mellitus is associated with adverse short- and long-term consequences for both the mother and the offspring. To examine the relationship between the rates of gestational weight gain (RGWG) during early and mid-pregnancy and the risk of gestational diabetes mellitus (GDM). Methods 2090 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed in our study. Gestational weight were measured regularly in every antenatal visit. Gestational diabetes mellitus was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Multivariable logistic regression was performed to estimate effect of RGWG on GDM. Results A total of 8.3% (n = 173) of pregnant women were diagnosed with GDM. Women with elevated rate of gestational weight gain prior to glucose screening test (RGWG-PG) increased the risk of GDM (adjusted p -trend = 0.004; odds ratios (OR) 1.64, 95% confidence intervals (CI) 1.01–2.68 and OR 2.30,95% CI 1.44–3.66 for 0.297–0.384 kg/wk and 0.385 kg/wk or more vs. 0.213 kg/wk or less, respectively). Women with greater rate of gestational weight gain in the first trimester (RGWG-F) increased the risk of GDM (adjusted p -trend = 0.048; OR 1.83, 95% CI 1.14–2.94 and OR 1.76, 95% CI 1.10–2.83 for 0.086–0.200 kg/wk and 0.201 kg/wk or more vs. −0.025 kg/wk or less, respectively). The rate of gestational weight gain in the second trimester (RGWG-S) was significantly associated with GDM only among women with RGWG-F more than 0.086 kg/wk (adjusted p -trend = 0.035; OR 2.04, 95% CI 1.16–3.59 for 0.658 kg/wk or more vs. 0.418 kg/wk or less). Conclusions Greater early pregnancy weight gain are associated with increased risk of GDM. Elevated weight gain in mid-pregnancy increased the risk of GDM only among pregnant women with greater weight gain in the first trimester.

cope : Resveratrol has been shown to improve insulin resistance via activating the NAD+-dependent deacetylase SIRT1, but the effects of resveratrol on ethanol-induced insulin resistance remain unclear. This study was designed to explore the potential mechanism by which resveratrol ameliorated ethanol-induced insulin resistance, focusing on its regulations on the ratio of NAD+/NADH and SIRT1 expression. Methods and results : Male Sprague–Dawley rats were fed either control or ethanol liquid diets containing 0.8, 1.6 and 2.4 g/kg·bw ethanol with or without 100 mg/kg·bw resveratrol for 22 weeks. Resveratrol improved ethanol (2.4 g/kg·bw) induced reductions in insulin sensitivity, SIRT1 expression (51%, P < 0.05), NAD+/NADH ratio (196%, P < 0.01) as well as the expression and activity of ALDH2 while decreased the augmentations in the expression and activity of ADH and CYP2E1. In primary rat hepatocytes, ethanol exposure (25 mmol/L, 24 hours) similarly decreased SIRT1 expression and NAD+/NADH ratio (33%, P < 0.05, 32%, P < 0.01), and 0.1 μmol/L resveratrol treatment reversed these decreases and inhibited the expressions of ADH and CYP2E1. Conclusion : Resveratrol exhibits benefits against ethanol-induced insulin resistance via improving the ratio of NAD+/NADH to regulate SIRT1, which is associated with the modulation of ethanol metabolism enzymes. This article is protected by copyright. All rights reserved

OBJECTIVES: Whether delayed onset of lactogenesis (delayed OL) was linked to successful breastfeeding is unclear. We aimed to assess the association between delayed OL and breastfeeding practices in Chinese women. METHODS: Women form the TMCHC (Tongji Maternal and Child Health Cohort) study, who had OL assessment by face-to-face interview at day 4 postpartum and breastfeeding practices collected at 3, 6 and 12 months postpartum, were selected for the study. Poisson regression and Cox regression were used to identify the association between delayed OL and breastfeeding practices. RESULTS: Delayed OL was reported by 17.7% of the 2691 participants. After adjusting for maternal age, ethnicity, education, income, parity, pre-pregnancy BMI, GDM, gestational weight gain, gestational age, delivery mode, birth weight and breastfeeding information at day 1 postpartum, delayed OL was significantly associated with a higher risk of an inability to sustain full breastfeeding at 3 months postpartum (RR:1.31, 95% CI: 1.16, 1.48) and 6 months postpartum (RR:1.17, 95% CI: 1.07, 1.28), when compared with timely OL. Delayed OL was also significantly associated with early termination of any breastfeeding (HR:1.17, 95% CI: 1.01, 1.34) in adjusted model. CONCLUSIONS: This study shows that women with delayed OL had a higher risk of suboptimal breastfeeding practices. Comprehensive efforts should be targeted towards women with delayed OL to promote breastfeeding. FUNDING SOURCES: Funding was received from National Program on Basic Research Project of China (NO.2013FY114200) and the Fundamental Research Funds for the Central Universities (HUST2016YXZD040) for Nianhong Yang. Supporting Tables, Images and/or Graphs

Iodine excess is emerging as a new focus. A better understanding of its hazardous effects on the liver will be of great benefit to health. The aim of this study is to illustrate the effects of iodine excess on hepatic lipid homeostasis and explore its possible mechanisms. One hundred twenty BaLB/c mice were given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/L) in drinking water for 1 or 3 months. Lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. The mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) was detected by real-time polymerase chain reaction. Dose-dependent increase of hepatic triglyceride content was detected (r = 0.680, P

Lipid metabolic disorders are widely considered to be one of the most critical and basic link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to illustrate the alleviation function of resveratrol (Res) on NAFLD and the roles of hepatic fatty acid synthase (FAS), low density lipoprotein receptor (LDLr), scavenger receptor class B type I (SR-BI), and thyroid hormone receptor β1 (TRβ1), which are the key molecules involved in lipid metabolism. Adult male Wistar rats were fed a normal diet or high fat/sucrose diet (HFS) with or without resveratrol for 13 weeks. HFS induced NAFLD formation and increased the lipids concentrations in serum and livers of rats, while noticeable improvement has been reached by Res intervention. Moreover, Res protected against HFS-induced decrease in hepatic LDLr and SR-BI mRNA and protein expressions, whereas TRβ1 expressions were impervious with/without Res. Unexpectedly, hepatic FAS gene expressions were markedly diminished in NAFLD rats and were gradually increased by treatment with Res. These data indicate that the alleviative effects of Res on NAFLD are associated with up regulation of hepatic LDLr and SR-BI gene expressions, which provide new insights into the pharmacological targets of Res in the prevention of NAFLD.

There have been many studies on the nutrition and the growth status of children from rural and remote western regions of China, whereas researches on children from urban low-income families are scarce. This study aimed to investigate the growth and nutritional status of children under five years of age from urban low-income families in China. There were 169 children aged 25-60 months recruited from Xiangtan and Jilin, two cities with a population of 2.81 million and 4.26 million respectively, in China in this cluster cross-sectional study. Data were collected on demographic and socioeconomic characteristics, the feeding practices and the incidence of anemia and diarrhea. The results showed that the prevalence of low birth weight and macrosomia was 7.1% and 9.5% for the two cities, respectively, which was higher than that for other cities in China (1.5% and 5.9%). Of all the sampled children, 14.6% and 8.2% suffered anemia and diarrhea, respectively. Multivariate analysis showed that legumes or nuts fed in a 24-h recall increased the risk of anemia (OR=4.9). Children whose caregivers began to introduce complementary foods relatively late would have high diarrhea prevalence (OR=1.4). In conclusion, the prevalence of anemia and diarrhea in under-five children from urban low-income families in China is relatively high. The growth and nutritional status of these children is greatly affected by feeding practices. A series of measures should be taken by relevant government departments to improve the health of these children.

Objective Senescence of vascular cells contributes to the development of cardiovascular diseases and the overall aging. This study was undertaken to investigate the effects of resveratrol (Res) on amelioration of vascular cell aging and the role of SIRT1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathway. Methods and Results Adult male Wistar rats were treated with a high-fat/sucrose diet (HFS) in the presence or absence of Res for 3 months. HFS and in vitro treatment with high glucose increased the senescence cells and reactive oxygen species production in rat aorta and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Res protected against HFS- or high-glucose-induced increase in NADPH oxidase p47phox expression and decrease in SIRT1 level. Apocynin, a NADPH oxidase inhibitor, down-regulated p47phox protein expression, but had no influence on SIRT1 protein; sirtinol, a SIRT1 inhibitor, aggravated the decrease in SIRT1 protein level and the increase in p47phox protein expression induced by high glucose. Conclusion Our studies suggested that Res was able to reverse the senescence process in aorta induced by HFS in rats or induced by the exposure to high glucose in cultured BAECs. The underlying mechanism is at least SIRT1/NADPH oxidase pathway dependent.

The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 μg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p