Publications by authors named "Ya-Shu Kuang"

11 Publications

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Identification of maternal continuous glucose monitoring metrics related to newborn birth weight in pregnant women with gestational diabetes.

Endocrine 2021 Jun 14. Epub 2021 Jun 14.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Purpose: To identify the specific glucose metrics derived from maternal continuous glucose monitoring (CGM) data, which were associated with a higher percentile of offspring birth weight.

Methods: In this cohort study, we recruited singleton pregnant women with GDM who underwent CGM for 5-14 days at a mean of 28.8 gestational weeks between Jan 2017 and Nov 2018. Commonly used single summary glucose metrics of glucose exposure (including mean 24-h, daytime, and nighttime glucose level) and variability (including J-index and mean amplitude of glycaemic excursions) were derived from CGM data. A novel comprehensive glucose metric-hours per-day spent in a severe variability glucose mode (HSSV)-was identified using the spectral clustering method, which reflects both glucose level and variability. Multiple linear regression models were used to estimate the associations of sex- and gestational age-adjusted birth weight percentile with CGM parameters.

Results: Ninety-seven women comprising 127,279 glucose measurements were included. Each 1-SD increase in maternal nighttime mean glucose level and HSSV was associated with 6.0 (95% CI 0.4, 11.5) and 6.3 (95% CI 0.4, 12.2) percentage points increase in birth weight percentile, respectively. No associations were found between other glucose metrics and birth weight percentile.

Conclusion: Nighttime mean glucose level has a comparable effect size to HSSV in association with fetal growth, suggesting that endogenous hyperglycemia might drive the association between maternal hyperglycemia and birth weight. Further studies need to examine the effect of lowering nighttime glucose level and/or HSSV on preventing fetal overgrowth in GDM women.
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http://dx.doi.org/10.1007/s12020-021-02787-xDOI Listing
June 2021

Maternal circulating leptin profile during pregnancy and gestational diabetes mellitus.

Diabetes Res Clin Pract 2020 Mar 29;161:108041. Epub 2020 Jan 29.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China; Department of Woman and Child Health Care, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China; Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China. Electronic address:

Aims: To evaluate the difference in maternal circulating leptin profile between pregnant women with and without gestational diabetes mellitus (GDM).

Methods: This is a nested case-control study embedded in the Born in Guangzhou Cohort Study in Guangzhou Women and Children's Medical Center, with 198 GDM cases and 192 controls included. Maternal plasma leptin profile was defined as leptin concentrations measured at early (baseline) and late pregnancy, as well as a ratio of concentration at late to that at early pregnancy (RL1L0). General linear regression was used to assess the associations between GDM and log-transformed leptin measurements.

Results: Women with GDM had a higher baseline leptin concentration and lower RL1L0 compared to those without GDM. The log leptin concentration at baseline (β: 0.19, 95%CI: 0.04, 0.34) and the log RL1L0 (β: -0.22, 95%CI: -0.41, -0.03) were associated with GDM status. The RL1L0 decreased significantly along with the increase of 1-hour glucose and the difference between 1-hour and fasting glucose levels in both GDM and non-GDM women.

Conclusions: Women with GDM had a certain profile of circulating leptin, with higher baseline concentration but less increase during pregnancy, suggesting an impaired compensatory response to increasing insulin resistance along with the progress of pregnancy.
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http://dx.doi.org/10.1016/j.diabres.2020.108041DOI Listing
March 2020

-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction.

Oncotarget 2017 Dec 15;8(69):114300-114313. Epub 2017 Dec 15.

Department of Cardiology, Shanghai Tongji Hospital, Tongji University, Shanghai, China.

Background: Endothelial microparticles (EMPs) are small vesicles released by endothelial cells (ECs); they are considered biomarkers for endothelial dysfunction and therapeutic targets in diabetes-related vascular disease. Sirtuins have also been shown to play important roles in diabetes by regulating endothelial dysfunction. However, the effect of sirtuin-incorporated EMPs on their parental ECs remains unknown.

Aim: The present study aims to investigate the diagnostic value of EMPs in diabetes and detect the protective effects of () -incorporated EMPs on endothelial dysfunction.

Methods: EMPs were prepared from cultured HUVECs and venous blood from patients with diabetes (n=10) and from healthy volunteers (n=6) after sequential centrifugation. Adv- or siRNA was used to alter Sirt6 expression. EC angiogenesis, inflammatory phenotypes, nitric oxide (NO) formation and eNOS phosphorylation were used to evaluate endothelial dysfunction.

Results: The levels of EMPs in diabetic patients and high glucose-cultured HUVECs are high, whereas Sirt6 expression in plasma and EMPs is low. EMPs generated from diabetic patients or high glucose-cultured HUVECs increase inflammatory chemokine release and blunt EC angiogenesis. Furthermore, EMPs enriched with mRNA induces EC angiogenesis, increases eNOS phosphorylation and impedes inflammatory chemokine release. Inhibition of mRNA expression in EMPs by siRNA hinders angiogenesis and eNOS phosphorylation but increases cellular inflammation.

Conclusion: The -carrying EMPs may ameliorate endothelial dysfunction in diabetic patients.
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http://dx.doi.org/10.18632/oncotarget.23259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768405PMC
December 2017

Connections between the human gut microbiome and gestational diabetes mellitus.

Gigascience 2017 08;6(8):1-12

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, China.

The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.
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http://dx.doi.org/10.1093/gigascience/gix058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597849PMC
August 2017

Associations of maternal PLA2G4C and PLA2G4D polymorphisms with the risk of spontaneous preterm birth in a Chinese population.

Mol Med Rep 2017 Jun 12;15(6):3607-3614. Epub 2017 Apr 12.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.

Preterm birth is the leading cause of mortality and morbidity in infants. Its etiology is multifactorial with genes and immune homeostasis. The authors investigated whether prostaglandin (PG) synthesis related single nucleotide polymorphisms (SNPs) PLA2G4C rs1366442 and PLA2G4D rs4924618 were associated with the risk of spontaneous preterm birth (SPTB) in a Chinese population of 114 cases of SPTB and 250 controls of term delivery. The risk associations were determined by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated using multivariate logistic regression. Homology modeling was performed to elucidate potential mechanism of the SNP function. The maternal AT/TT genotype of PLA2G4D rs4924618 was associated with a reduced risk of SPTB (OR, 0.61; 95% CI, 0.37‑0.99), while no significant association between PLA2G4C rs1366442 and SPTB risk was identified. Structure and sequence analysis revealed that the amino acid substitution introduced by this SNP located at the conserved central core of the catalytic domain of cytosolic phospholipase A2 δ and was close to the active site. These findings suggested that the polymorphism of PLA2G4D rs4924618 may have a protective influence on the SPTB susceptibility in a Chinese population, supporting a role for genetics in the association between PG synthesis and preterm birth.
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http://dx.doi.org/10.3892/mmr.2017.6475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436275PMC
June 2017

The Born in Guangzhou Cohort Study (BIGCS).

Eur J Epidemiol 2017 04 20;32(4):337-346. Epub 2017 Mar 20.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Junsui Road, Zhujiang Newtown, Tianhe District, Guangzhou, 510623, China.

The Born in Guangzhou Cohort Study (BIGCS) is a large-scale prospective observational study investigating the role of social, biological and environmental influences on pregnancy and child health and development in an urban setting in southern China. Pregnant women who reside in Guangzhou and who attend Guangzhou Women and Children's Medical Center (GWCMC) for antenatal care in early pregnancy (<20 weeks' gestation) are eligible for inclusion. Study recruitment commenced in February 2012, with an overall participation rate of 76.3%. Study recruitment will continue until December 2018 to achieve the target sample size of 30,000 mother-child pairs. At 30 April 2016, a total of 75,422 questionnaires have been collected, while 14,696 live births have occurred with planned follow-up of cohort children until age 18 years. During the same period a total of 1,053,000 biological samples have been collected from participants, including maternal, paternal and infant blood, cord blood, placenta, umbilical cord, and maternal and infant stool samples. The dataset has been enhanced by record linkage to routine health and administrative records. We plan future record linkage to school enrolment and national examination records.
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http://dx.doi.org/10.1007/s10654-017-0239-xDOI Listing
April 2017

Maternal IGF1 and IGF1R polymorphisms and the risk of spontaneous preterm birth.

J Clin Lab Anal 2017 Nov 18;31(6). Epub 2017 Feb 18.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Background: The insulin-like growth factor (IGF) pathway was involved in the occurrence of spontaneous preterm birth (SPTB), but little is known regarding the relationship between genetic variations in IGF pathway and the risk of SPTB. We aimed to investigate the associations of IGF1 rs972936 and IGF1 receptor (IGF1R) rs2229765 polymorphisms with SPTB risk in a Chinese population.

Method: A total of 114 cases of SPTB and 250 controls of term delivery were included from Guangzhou Women and Children's Medical Center, China. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using multivariate logistic regression.

Results: We found that the GA and GA/AA genotypes of IGF1 rs972936 were associated with an increased risk of SPTB, and the adjusted ORs (95% CI) were 1.74 (1.01-3.02) and 1.75 (1.04-2.93) respectively. Women carrying GA and GA/AA genotypes of IGF1R rs2229765 had a reduced risk compared to those with the GG genotype (0.60 [0.37-0.98] and 0.64 [0.40-1.00] respectively). There were significant interactions between IGF1 rs972936 and GDM status (P for interaction=.02), as well as between IGF1R rs2229765 and pre-pregnancy BMI (P for interaction <.001) on the risk of SPTB.

Conclusion: Our findings suggest that polymorphisms of IGF1 rs972936 and IGF1R rs2229765 were associated with the risk of SPTB in Chinese pregnant women and these effects depend on the maternal metabolic status.
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http://dx.doi.org/10.1002/jcla.22125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817009PMC
November 2017

Composition of gut microbiota in infants in China and global comparison.

Sci Rep 2016 11 9;6:36666. Epub 2016 Nov 9.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, People's Republic of China.

Symbiotic gut microbiota is essential for human health, and its compositional changes have been associated with various complex disorders. However, systematic investigation of the acquisition and development of gut microbial communities during early infancy are relatively rare, particularly for infants from non-Western countries. In this study, we characterize the colonization and development of infant microbiota in healthy Chinese infants and compare the pattern with those from other countries. The fecal microbiota of 2-month-old infants was considerably more diverse than that of neonates, as indicated by higher relative abundances of Veillonella, Clostridium, Bacteroides, Lactobacillus, Collinsella and Prevotella, and reduction of Escherichia and Enterococcus. The fecal microbiota of vaginally delivered infants (both neonates and 2-month-old) had significant enrichment of Bacteroides, Parabacteroides and Megamonas, whereas cesarean delivered infants had enrichment of Prevotella, Streptococcus and Trabulsiella. By global comparison, we identify three different enterotypes, referred as "P-type", "A-type "and "F-type" which were highly abundant in Proteobacteria, Actinobacteria and Firmicutes, respectively. The three enterotypes' compositons vary geographically. All Chinese infants in our study belong to the P-type. These findings may provide novel insights into our understanding of the establishment of infant fecal bacterial communities.
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http://dx.doi.org/10.1038/srep36666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101483PMC
November 2016

Effect of short-term room temperature storage on the microbial community in infant fecal samples.

Sci Rep 2016 05 26;6:26648. Epub 2016 May 26.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.

Sample storage conditions are important for unbiased analysis of microbial communities in metagenomic studies. Specifically, for infant gut microbiota studies, stool specimens are often exposed to room temperature (RT) conditions prior to analysis. This could lead to variations in structural and quantitative assessment of bacterial communities. To estimate such effects of RT storage, we collected feces from 29 healthy infants (0-3 months) and partitioned each sample into 5 portions to be stored for different lengths of time at RT before freezing at -80 °C. Alpha diversity did not differ between samples with storage time from 0 to 2 hours. The UniFrac distances and microbial composition analysis showed significant differences by testing among individuals, but not by testing between different time points at RT. Changes in the relative abundance of some specific (less common, minor) taxa were still found during storage at room temperature. Our results support previous studies in children and adults, and provided useful information for accurate characterization of infant gut microbiomes. In particular, our study furnished a solid foundation and justification for using fecal samples exposed to RT for less than 2 hours for comparative analyses between various medical conditions.
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http://dx.doi.org/10.1038/srep26648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880902PMC
May 2016

C1q and tumor necrosis factor-related protein 3 is present in human cord blood and is associated with fetal growth.

Clin Chim Acta 2016 Jan 2;453:67-70. Epub 2015 Dec 2.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address:

Background: To determine the presence of C1q and tumor necrosis factor-related protein 3 (CTRP3) in cord blood and its relationship with fetal growth among Chinese newborns.

Methods: This pilot study recruited 126 infants (small for gestational age [SGA], n=34; appropriate for gestational age [AGA], n=60; large for gestational age [LGA], n=32); cord blood CTRP3 levels were measured, and fetal growth parameters were collected.

Results: Median (25-75th percentile) CTRP3 levels in the SGA, AGA, and LGA groups were 297.2 (236.4-360.2), 297.5 (261.0-369.9), and 368.6 (298.5-507.1) ng/ml, respectively (P=0.01). LGA infants had higher CTRP3 levels than AGA infants (multiple linear regression analysis; P=0.01). The CTRP3 levels were positively correlated with birth weight (r=0.25, P<0.01), Ponderal index (r=0.28, P<0.01), and placental weight (r=0.20, P=0.03) in the total study population. In the subgroup analysis, CTRP3 levels were negatively correlated with birth length z scores (r=-0.39, P=0.03) and were positively correlated with the Ponderal index (r=0.43, P=0.02) only in the SGA group; no other significant correlations were observed. The CTRP3 levels were similar between the sexes (P=NS).

Conclusions: CTRP3 is present in cord blood and might be involved in fetal growth.
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http://dx.doi.org/10.1016/j.cca.2015.11.031DOI Listing
January 2016

Relationship between human cord blood adropin levels and fetal growth.

Peptides 2014 Feb 24;52:19-22. Epub 2013 Nov 24.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou, China. Electronic address:

Adropin is a recently identified peptide and participates in the regulation of energy homeostasis and vascular function. The aim of this study was to examine the relationships between human cord blood adropin levels and fetal growth. A total of 159 newborns [preterm delivery (PTD), n=72; term delivery, n=87] were recruited. Adropin levels in cord blood were determined using enzyme-linked immunosorbent assay kits. Clinical information on fetal growth was collected. Adropin levels in PTD babies (median, 2028; 25th-75th, 1413-2484pg/ml) were lower than those in term delivery babies (median, 2305; 25th-75th, 1960-2684pg/ml, P=0.01). Birth weight and length z score, Ponderal index, placental length, breadth, thickness, surface area, volume and density were not significantly correlated to adropin concentrations in term delivery group. However, we found adropin concentrations were significantly correlated to gestational age at birth (Spearman's correlation coefficient=0.35, P<0.01) and placental weight (Spearman's correlation coefficient=0.24, P=0.04) in PTD group. We also found that boys had lower adropin levels than girls in PTD group (P=0.01). When the analysis was extended to the whole group (PTD and term deliveries combined), the results were similar to those for PTD group alone. After adjusting for maternal age and newborn's sex, every 100pg/ml increase of adropin concentration was significantly associated with a decreased risk of PTD (odds ratio, 0.95; 95% confidence interval, 0.91-0.99). Our study showed that cord blood adropin levels were positively correlated with gestational age and placental weight but not with other fetal growth parameters.
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http://dx.doi.org/10.1016/j.peptides.2013.11.013DOI Listing
February 2014
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