Certain perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental contaminants. Prenatal PFAS exposure has been associated with lower birth weight; however, ...impacts on body composition and factors responsible for this association are unknown.
We aimed to estimate associations between maternal PFAS concentrations and offspring weight and adiposity at birth, and secondarily to estimate associations between PFAS concentrations and maternal glucose and lipids, and to evaluate the potential for these nutrients to mediate associations between PFAS and neonatal outcomes.
Within the Healthy Start prospective cohort, concentrations of 11 PFAS, fasting glucose, and lipids were measured in maternal mid-pregnancy serum (n=628). Infant body composition was measured using air displacement plethysmography. Associations between PFAS and birth weight and adiposity, and between PFAS and maternal glucose and lipids, were estimated via linear regression. Associations were decomposed into direct and indirect effects.
Five PFAS were detectable in >50% of participants. Maternal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) concentrations were inversely associated with birth weight. Adiposity at birth was approximately 10% lower in the highest categories of PFOA, PFNA, and perfluorohexane sulfonate (PFHxS) compared to the lowest categories. PFOA, PFNA, perfluorodecanoate (PFDeA), and PFHxS were inversely associated with maternal glucose. Up to 11.6% of the effect of PFAS on neonatal adiposity was mediated by maternal glucose concentrations. Perfluorooctane sulfonate (PFOS) was not significantly associated with any outcomes studied.
Follow-up of offspring will determine the potential long-term consequences of lower weight and adiposity at birth associated with prenatal PFAS exposure. https://doi.org/10.1289/EHP641.
Gut microbiota phenotypes of obesity Stanislawski, Maggie A; Dabelea, Dana; Lange, Leslie A ...
NPJ biofilms and microbiomes,
07/2019, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Obesity is a disease with a complex etiology and variable prevalence across different populations. While several studies have reported gut microbiota composition differences associated with obesity ...in humans, there has been a lack of consistency in the nature of the reported changes; it has been difficult to determine whether methodological differences between studies, underlying differences in the populations studied, or other factors are responsible for this discordance. Here we use 16 S rRNA data from previously published studies to explore how the gut microbiota-obesity relationship varies across heterogeneous Western populations, focusing mainly on the relationship between (1) alpha diversity and (2)
relative abundance with BMI. We provide evidence that the relationship between lower alpha diversity and higher BMI may be most consistent in non-Hispanic white (NHW) populations and/or those with high socioeconomic status, while the relationship between higher
relative abundance and BMI may be stronger among black and Hispanic populations. We further examine how diet may impact these relationships. This work suggests that gut microbiota phenotypes of obesity may differ with race/ethnicity or its correlates, such as dietary components or socioeconomic status. However, microbiome cohorts are often too small to study complex interaction effects and non-white individuals are greatly underrepresented, creating substantial challenges to understanding population-level patterns in the microbiome-obesity relationship. Further study of how population heterogeneity influences the relationship between the gut microbiota and obesity is warranted.
To estimate the prevalence of diabetes in U.S. youth aged <20 years in 2009 and to estimate the total number of youth with diabetes in the U.S. by age, race/ethnicity, and diabetes type.
To address ...one of its primary aims, the SEARCH for Diabetes in Youth Study identified youth aged <20 years on 31 December 2009 with physician-diagnosed diabetes in selected areas of Colorado, Ohio, South Carolina, and Washington, among health plan members of Kaiser Permanente Southern California and among American Indians living on reservations in Arizona and New Mexico. Diabetes was classified as type 1, type 2, or other. Race/ethnicity was by self-report.
From a population of 3,458,974 youth aged <20 years, 7,695 youth with diabetes were identified (2.22/1,000): 6,668 with type 1 diabetes (1.93/1,000), 837 with type 2 diabetes (0.24/1,000), and 190 (0.05/1,000) with other diabetes types. Prevalence increased with age, was slightly higher in females than males, and was most prevalent in non-Hispanic White and least prevalent in Asian/Pacific Islanders, with Native American and black youth having the highest prevalence of type 2 diabetes. An estimated 191,986 U.S. youth aged <20 years have diabetes; 166,984 type 1 diabetes, 20,262 type 2 diabetes, and 4,740 other types.
Diabetes, one of the leading chronic diseases in childhood, affects >190,000 (1 of 433) youth aged <20 years in the U.S., with racial and ethnic disparities seen in diabetes prevalence, overall and by diabetes type.
Aims/hypothesis
The aim of this work was to investigate the association of maternal HbA
1c
during mid-pregnancy with biomarkers of glucose–insulin homeostasis during early childhood (4–7 years of ...age) and to assess whether and how offspring adiposity at birth and at age 4–7 years mediates this relationship among 345 mother–child pairs in the Healthy Start Study.
Methods
The exposure was maternal HbA
1c
(mmol/mol) measured at 20–34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4–7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4–7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex.
Results
There was a significant total effect of maternal HbA
1c
on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA
1c
and offspring glucose (
p
trend <0.001), and an inverse trend across tertiles of HbA
1c
and offspring 1/insulin (
p
trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA
1c
, those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI −0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4–7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage.
Conclusions/interpretation
Offspring of women with higher HbA
1c
during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child’s own adiposity.
Graphical abstract
Aims:
Our study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify ...youth with maturity-onset diabetes of the young (MODY).
Methods:
The SEARCH for Diabetes in Youth study is a US multicenter, population-based study of youth with diabetes diagnosed at age younger than 20 years. We sequenced genomic DNA for mutations in the HNF1A, HNF4A, and glucokinase genes in 586 participants enrolled in SEARCH between 2001 and 2006. Selection criteria included diabetes autoantibody negativity and fasting C-peptide levels of 0.8 ng/mL or greater.
Results:
We identified a mutation in one of three MODY genes in 47 participants, or 8.0% of the tested sample, for a prevalence of at least 1.2% in the pediatric diabetes population. Of these, only 3 had a clinical diagnosis of MODY, and the majority was treated with insulin. Compared with the MODY-negative group, MODY-positive participants had lower FCP levels (2.2 ± 1.4 vs 3.2 ± 2.1 ng/mL, P < .01) and fewer type 2 diabetes-like metabolic features. Parental history of diabetes did not significantly differ between the 2 groups.
Conclusions/Interpretation:
In this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.
Prenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that ...faster growth in early infancy may be associated with maternal PFAS concentrations.
Among 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5 months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression.
Associations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5–1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5 months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (−0.26 SD per ln-ng/mL PFOS, 95% CI −0.43, −0.10; −0.17 SD per ln-ng/mL PFHxS, 95% CI −0.33, −0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio OR 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations.
We observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass.
•Associations between maternal PFAS and infant weight and adiposity differed by sex.•Prenatal PFOA and PFNA were associated with greater 5-month adiposity in males.•Prenatal PFOS and PFHxS were associated with lower weight-for-age in females.•MeFOSAA was associated with greater odds of rapid growth from 0 to 5 months of age.
Objective To describe the prevalence of access and process barriers to health care and to examine their relationship to sociodemographic and disease factors in a large and diverse cohort of US youth ...with type 1 diabetes. Study design A cross-sectional analysis of 780 youth who participated in the SEARCH for Diabetes in Youth Study and were diagnosed with type 1 diabetes in 2002-2005. Experience of barriers to care was collected from parent report on questionnaires. Analyses included multivariate regression models to predict the presence of specific barriers to care. Results Overall, 81.7% of participants reported at least one barrier; the 3 most common were costs (47.5%), communication (43.0%), and getting needed information (48.4%). Problems with access to care, not having a regular provider, and receiving contextual care (care that takes into account personal and family context) were associated with poorer glycated hemoglobin levels. Adjusted multivariate models indicated that barriers related to access (regular provider, cost) were most likely for youth with low family income and those without public health insurance. Barriers associated with the processes of quality care (contextual care, communication) were more likely for Hispanic youth and those whose parents had less education. Conclusions This study indicates that a large proportion of youth with type 1 diabetes experience substantial barriers to care. Barriers to access and those associated with processes of quality care differed by sociodemographic characteristics. Future investigators should expand knowledge of the systemic processes that lead to disparate outcomes for some youth with diabetes and assess potential solutions.
Childhood obesity is a growing problem worldwide. Recent research suggests that the gut microbiota may play an important and potentially causal role in the development of obesity and may be one ...mechanism that explains the transgenerational transmission of obesity risk. Here we examine the early-life gut microbiota at days 4, 10, 30, 120, 365, and 730 and the association with body mass index (BMI) z-scores at age 12 in a Norwegian prospective cohort (
= 165), and evaluate how these BMI-associated taxa relate to maternal overweight/obesity (Ow/Ob) and excessive gestational weight gain (GWG). We performed 16S rRNA gene sequencing on the gut microbiota samples. Taxonomic phylogeny at days 10 and 730 was significantly associated with childhood BMI, and the gut microbiota taxa at two years of age explained over 50% of the variation in childhood BMI in this cohort. The subset of the early-life taxa within the gut microbiota that best predicted later childhood BMI showed substantial overlap with the maternal taxa most strongly associated with maternal Ow/Ob and excessive GWG. Our results show an association between the infant gut microbiota and later BMI, and they offer preliminary evidence that the infant gut microbiota, particularly at 2 years of age, may have potential to help identify children at risk for obesity.
Understanding the role of the early-life gut microbiota in obesity is important because there may be opportunities for preventive strategies. We examined the relationships between infant gut microbiota at six times during the first two years of life and BMI at age 12 in a birth cohort of 165 children and their mothers. We found that the gut microbiota from early life to two years shows an increasingly strong association with childhood BMI. This study provides preliminary evidence that the gut microbiome at 2 years of age may offer useful information to help to identify youth who are at risk for obesity, which could facilitate more-targeted early prevention efforts.
Abstract Purpose To evaluate the psychosocial burden of adolescents with diabetes, determine the trajectory of psychosocial burden, and examine the interdependent relationships between psychosocial ...burden and glycemic control across the first 6 years of diabetes. Methods Data from SEARCH for Diabetes in Youth, an observational study of U.S. children diagnosed with diabetes before the age of 20, were collected during study visits conducted at baseline and then at 12, 24, and 60 months after baseline. Blood was drawn, clinical and demographic information was collected, and psychosocial burden was evaluated using standardized depression and generic and diabetes-specific health-related quality of life (QOL) surveys. Results Among the 1,307 adolescents (mean age, 14.1±2.5 years) with baseline data, 1,026 had type 1 diabetes and 281 had type 2 diabetes. For those with a 60-month follow-up visit, glycated hemoglobin (A1c ) values rose 1.5% from baseline (type 1, 7.7%–9.3% and type 2, 7.3%–8.8%). Adolescents with type 2 diabetes reported more depression and poorer QOL than adolescents with type 1 diabetes. For each diabetes type, there were similar baseline risk factors for higher A1c values: longer diabetes duration, ethnic minority status, and declining diabetes QOL ( p < .05). However, youth with type 2 diabetes had higher A1c values with increasing generic QOL, an unexpected finding. Younger adolescents with type 1 diabetes had higher A1c values at the end of the study. Conclusions Significant deterioration in glycemic control marks the first 6 years of diabetes for adolescents. Psychosocial burden, particularly poor diabetes-specific QOL, is a contributor to suboptimal glycemic outcomes.
Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in ...children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype.
We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators.
Among 583 mother-infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate
and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted
). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin.
Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (
). Methylation at one DMP (cg18587484), annotated to the gene
, was associated with perfluorooctanoate (PFOA) at
. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (
), lipid homeostasis (
,
,
,
), inflammation and immune activity (
,
), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (
).
DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888.
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