Prenatal exposure to per- and polyfluoroalkyl substances: Association with child behavior in the environmental influences on child health outcomes (ECHO) Cohort.

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely impact child neurodevelopment; however, epidemiologic findings remain inconclusive because of small sample sizes, limited exposure variability, and differing neurodevelopmental measures. We aimed to investigate the relationship between prenatal PFAS exposure and child behavior.

Methods: We pooled data from nine study sites in the nationwide Environmental influences on Child Health Outcomes (ECHO) Cohort.

A Randomised Controlled Trial Testing a Behavioural Intervention Program for the Prevention of Type 2 Diabetes Among American Indian Youth: The Tribal Turning Point Study.

Background: American Indian youth experience a high risk of overweight/obesity and type 2 diabetes.

Objectives: To evaluate the effect of a behavioural intervention on diabetes risk factors among American Indian youth with overweight/obesity.

Methods: Between 2018 and 2023, youth (7-10 years) were randomised to the tribal turning point (TTP) intervention (n = 87) or control arm (n = 95).

Environmental phenol mixture during pregnancy and child sleep quality in the ECHO cohort.

Introduction: Poor sleep quality in childhood can predict sleep quality throughout the lifecourse and other health outcomes. Endocrine-disrupting chemicals can affect adults' sleep quality, and prenatal phenol exposure impacts fetal development.

Objective: To assess associations between prenatal phenol concentrations and child sleep outcomes.

Analysis of Long-term Follow-up of a Randomized Clinical Trial With Departures From Assigned Treatments: Estimation of Metformin Effects on Diabetes and Its Complications in the Diabetes Prevention Program Outcomes Study.

The Diabetes Prevention Program (DPP) was a 3-year randomized clinical trial (RCT) with evaluation of lifestyle and metformin interventions compared with placebo for diabetes prevention in high-risk adults. Both interventions significantly reduced diabetes incidence, prompting the long-term Diabetes Prevention Program Outcomes Study (DPPOS) to assess the progression of diabetes and its complications over 22 years. During follow-up, departures from the original metformin or placebo assignment occurred primarily because of development of diabetes that, by protocol, was managed by clinicians outside the study, after participants developed diabetes with HbA1c ≥7.

Healthcare and non-healthcare costs: youth with diabetes and food insecurity.

Introduction: This study prospectively evaluated the association of household food insecurity and acute care costs and productivity loss in youth and young adults (YYA) with type 1 and type 2 diabetes.

Methods: This observational cohort study included 1,256 YYA with type 1 and type 2 diabetes from the SEARCH for Diabetes in Youth Food Security Study with data collected at three time points between 2015-2022. Both household food insecurity (HFI, measured using the US Household Food Security Survey Module) and costs (measured using survey responses on utilization and productivity losses) were self-reported by young adult participants or caregivers of adolescents.

Responsiveness of the Serum Carbon Isotope Ratio to Dietary Added Sugar Reduction in a Randomized Controlled Trial among Youth with Steatotic Liver Disease.

Background: The carbon isotope ratio (CIR) has been proposed as a biomarker for added sugar intake, but few studies have been conducted in youth, with data from controlled, feeding studies particularly lacking.

Objectives: This study aims to examine associations of added sugar intake with serum CIR in a randomized, controlled dietary sugar reduction intervention in youth.

Methods: Data were collected from 40 boys (11-16 y) with histologically diagnosed steatotic liver disease who completed a randomized controlled trial and were provided either a low-free sugar diet (<3% of calories from added sugar or juice) or usual diet for 8 wk.

The impact of ancestry on performance of type 1 diabetes genetic risk scores: high discrimination performance is maintained in African ancestry populations, but population specific thresholds may improve risk prediction.

Objective: Genetic risk scores (GRSs) for type 1 diabetes (T1D) may assist T1D classification and prediction but are often developed from European populations. To improve health outcomes, it is important to understand the performance and utility of GRSs in diverse ancestry populations.

Research Design And Methods: We assessed performance of three previously published T1D GRSs in differentiating people with and without Type 1 diabetes in African (with/without T1D=194/235), European (n=1109/125), and Hispanic (266/170) ancestry populations in the USA, and from Cameroon and Uganda (n=144/5001).

Non-autoimmune, insulin-deficient diabetes in children and young adults in Africa: evidence from the Young-Onset Diabetes in sub-Saharan Africa (YODA) cross-sectional study.

Background: Studies of type 1 diabetes in sub-Saharan Africa have suggested that the clinical phenotype might differ from phenotypes reported elsewhere. We aimed to establish whether type 1 diabetes diagnosed in children and young adults in three countries across sub-Saharan Africa is of autoimmune origin.

Methods: In this observational, cross-sectional study, we identified participants without obesity from outpatient clinics in government and private hospitals in Cameroon, Uganda, and South Africa who were of self-reported Black African ethnicity with young-onset (age <30 years), insulin-treated, clinically diagnosed type 1 diabetes.

Prenatal opioid exposure and the early life epigenome: results from ECHO.

Background: Prenatal opioid exposure has been associated with adverse child health outcomes. Changes to the epigenome provide a plausible mechanism through which effects may be elicited. We investigated whether prenatal opioid exposure was associated with locus-specific changes in umbilical cord blood DNA methylation (DNAm) and gestational epigenetic age.

Residing in a low-income-low-food-access neighbourhood and asthma in early and middle childhood in the Environmental influences on Child Health Outcomes (ECHO) program: a multisite cohort study.

Importance: Access to healthy and affordable foods may play a role in reducing inflammation and in healthy pulmonary immune system development.

Objective: To investigate the association between residing in a low-income and low-food-access (LILA) neighbourhood and risk of childhood asthma. A positive association was hypothesised.

Disparities in the association of ambient air pollution with childhood asthma incidence in the ECHO consortium: A US-wide multi-cohort study.

Background: Characterization of US sociodemographic disparities in air pollution respiratory effects has often been limited by lack of participant diversity, geography, exposure characterization, and small sample size.

Methods: We included 34 sites comprising 23,234 children (born 1981-2021) from the Environmental influences on Child Health Outcomes (ECHO) Program with data on asthma diagnosis until age 10 (182,008 person-years). Predicted annual exposure to fine particulate matter (1988-2021), nitrogen dioxide (2000-2016), and ground ozone (2000-2016) were assigned based on residential histories.

Racial/ethnic-derived maternal diets predict birth outcomes better than a diet derived from a combined sample among Hispanic/Latina and non-Hispanic White pregnant individuals in the ECHO Cohort.

Little is known about diet based on maternal fasting blood glucose (FBG) and birth outcomes in diverse populations. We hypothesized that racial/ethnic-derived FBG-based diets would predict birth outcomes better than a diet derived from the overall sample. Pregnant Hispanic/Latina (n = 420) and non-Hispanic White (n = 564) individuals (combined, n=984) from two Environmental influences on Child Health Outcomes (ECHO) cohorts provided ≥ 1 24-h diet recalls.

Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood.

Background: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear.

Objective: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e.

GLP-1R Polymorphisms Modify the Relationship Between Exposure to Gestational Diabetes Mellitus and Offspring BMI Growth: The EPOCH Study.

Objective: Exposure to maternal gestational diabetes mellitus (GDM) is associated with childhood BMI. Among youth, we explored whether three different glucagon-like peptide 1 receptor gene (GLP-1R) polymorphisms modified the associations between 1) GDM and BMI trajectories and 2) GDM and markers of glucose-insulin homeostasis.

Research Design And Methods: For 464 participants from the Exploring Perinatal Outcomes Among Children (EPOCH) study, microarray genotyping was performed during childhood (∼10 years).

Newborn blood DNA methylation and childhood asthma: findings from the ECHO program.

Background: DNA methylation (DNAm) at birth has been linked to childhood asthma in epigenome-wide association studies (EWASs). However, existing EWASs have limited representation of non-European and extremely preterm participants and have not explored sex-specific DNAm differences. This study examined the association between DNAm in newborn blood and subsequent childhood asthma risk in a diverse population.

Global type 1 diabetes prevalence, incidence, and mortality estimates 2025: Results from the International diabetes Federation Atlas, 11th Edition, and the T1D Index Version 3.0.

Aims: Globally, symptomatic type 1 diabetes (T1D) prevalence varies markedly. The International Diabetes Federation 11thEdition Atlas/T1D Index Version 3.0 estimated 2025 numbers for 202 countries/territories ("countries"), and projected to2040.

Early-Life Factors and Body Mass Index Trajectories Among Children in the ECHO Cohort.

Importance: Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity.

Objective: To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors.

Design, Setting, And Participants: This cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments.

Prenatal per- and polyfluoroalkyl substance exposures and DNA methylation among newborns in the Environmental influences on Child Health Outcomes program.

Gestation is a vulnerable window when exposure to per- and polyfluoroalkyl substances (PFAS) may impact child development and health. Epigenetic modification, including DNA methylation (DNAm), may be one mechanism linking prenatal PFAS exposure to offspring outcomes. We tested associations between prenatal PFAS and newborn DNAm in 1017 participants from 6 cohorts in the US Environmental influences on Child Health Outcomes consortium.

Maternal Cardiometabolic Risk Factors in Pregnancy and Offspring Blood Pressure at Age 2 to 18 Years.

Importance: Higher blood pressure in early life may signal cardiovascular disease over the life course, but determinants of blood pressure in early life are poorly understood.

Objective: To examine the association of maternal cardiometabolic risk factors during pregnancy with offspring blood pressure from age 2 to 18 years and explore whether the association is modified by offspring sex and race and ethnicity.

Design, Setting, And Participants: This cohort study analyzed data from the Environmental Influences on Child Health Outcomes program between January 1, 1994, and March 31, 2023.

Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial.

Background: In the US Diabetes Prevention Program (DPP), a 3-year randomised clinical trial in 3234 adults with prediabetes, type 2 diabetes incidence was reduced by 58% with intensive lifestyle intervention (ILS) and by 31% with metformin, compared with placebo. We sought to assess the long-term effects and potential heterogeneity of treatment effects over approximately 21 years of follow-up.

Methods: The DPP trial was continued with protocol modifications as the DPP Outcomes Study (DPPOS).

Trends in CVD Risk Factors for Youth with Incident Diabetes: SEARCH for Diabetes in Youth.

Objectives: Cardiovascular disease (CVD) is the leading cause of death and disability among persons with diabetes. Early intervention on cardiovascular risk factors (CRFs) is important in reducing CVD burden. The SEARCH for Diabetes in Youth study assessed CRFs in incident cohorts of youth aged <20 years established from 2002 to 2016.

Youth-Onset Type 2 Diabetes: What We've Learned From Key Youth-Onset Type 2 Diabetes Studies, What We Still Don't Know, and Why It Is Important.

In this review, we describe the epidemiology, pathophysiology, pediatric-specific treatment response data, morbidity, and mortality of youth-onset type 2 diabetes. In recognition of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 75th anniversary, the focus is primarily on data from three landmark youth-onset type 2 diabetes studies funded by the NIDDK in the last 20+ years. We discuss the now-recognized aggressive clinical course of youth-onset type 2 diabetes, which only recently became appreciated as a pediatric disease among health care providers.

The Diabetes Prevention Program and Its Outcomes Study: NIDDK's Journey Into the Prevention of Type 2 Diabetes and Its Public Health Impact.

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes.

Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence over 21 Years of Follow-up in the Diabetes Prevention Program.

Unlabelled: Meta-analyses have reported a decrease in overall cancer incidence of approximately 10% to 40% with metformin use among individuals with diabetes. Lifestyle change could potentially reduce cancer incidence. The objective was to determine whether metformin or intensive lifestyle (ILS) intervention reduces the risk of cancer among adults at high risk of diabetes.

Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium.

Background: DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for health outcomes, how persistent epigenetic signals are across time, and whether epigenetic timing effects differ by outcome.

Methods: We applied longitudinal meta-regression models to published meta-analyses from the PACE consortium that examined DNAm at two timepoints-prospectively at birth and cross-sectionally in childhood-in relation to the same child outcome (ADHD symptoms, general psychopathology, sleep duration, BMI, asthma).