ABSTRACT
BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.
Subject(s)
Asthma , Male , Female , Adolescent , Humans , Child , Child, Preschool , Young Adult , Adult , Incidence , Asthma/etiology , Ethnicity , Prevalence , Outcome Assessment, Health CareABSTRACT
AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).
Subject(s)
Diabetes Mellitus, Type 2 , Population Health , Humans , Genome-Wide Association Study , Diabetes Mellitus, Type 2/genetics , Precision Medicine , Genotype , Hispanic or Latino/genetics , Polymorphism, Single Nucleotide/geneticsABSTRACT
In this exploratory analysis, we assessed whether nutrition modified the association between prenatal exposure to tobacco and childhood cognition/behavior among 366 Colorado-based mothers and their offspring (born ≥ 37 weeks with birthweights ≥ 2500 g). Interaction by folate (≥ 1074 µg/day) and breastfeeding (≥ 5 months) was assessed by including a product term with cotinine (≥ limit of detection [LOD]) in regression models for NIH Toolbox and Child Behavior Checklist T-scores. Main effects were observed between cotinine ≥ LOD and inhibitory control (- 3.2; 95% CI: - 6.8, 0.3), folate < 1074 µg/day and anxious/depressed symptoms (1.1; 95% CI: 0.1, 2.1), and breastfeeding < 5 months and receptive language (- 4.3; 95% CI: - 8.5, - 0.02), though these findings would not survive Bonferroni correction. Breastfeeding modified the tobacco-behavior associations. Sleep (3.8; 95% CI: 0.5, 7.1; interaction p-value = 0.02), depressive (4.6; 95% CI: 1.0, 8.2; interaction p-value = 0.01) and total problems (5.8; 95% CI: - 0.7, 12.4; interaction p-value = 0.09) were observed among tobacco-exposed offspring who breastfed > 5 months, but not for shorter durations. Our findings support the need for smoking cessation campaigns throughout pregnancy and throughout the postpartum period breastfeeding to reduce neurobehavioral risks in the offspring.
ABSTRACT
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.
Subject(s)
Diabetes Mellitus, Type 1/therapy , Health Services Accessibility/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Outcome Assessment, Health Care , Adolescent , Cross-Sectional Studies , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Ethnicity , Female , Health Knowledge, Attitudes, Practice , Humans , Logistic Models , Male , Multivariate Analysis , Prevalence , Primary Health Care/standards , Primary Health Care/trends , Risk Assessment , Severity of Illness Index , Socioeconomic Factors , Surveys and Questionnaires , United States , Young AdultABSTRACT
OBJECTIVE: In their Strategic Impact Goal Statement, the American Heart Association focused on primordial prevention of cardiovascular risk factors by defining metrics for ideal cardiovascular health (ICH). The prevalence of ICH among youth with type 1 diabetes is unknown. Youth with type 1 diabetes face an increased risk of cardiovascular disease (CVD) as they age. The purpose of this report was to examine the prevalence of ICH in a population of youth with type 1 diabetes and to examine the association of ICH with measures of cardiovascular structure and function. RESEARCH DESIGN AND METHODS: This report is based on SEARCH CVD an ancillary study to the SEARCH for Diabetes in Youth. A total of 190 adolescents with type 1 diabetes had complete data on all of the ICH metrics at baseline and had measures of arterial stiffness [pulse wave velocity (PWV), brachial distensibility (BrachD), and augmentation index (AIx)] and carotid intima-media thickness completed at a follow-up visit [on average 5 yr after baseline (interquartile range 4-5)]. RESULTS: No subjects met the ICH criteria for all 7 metrics. Meeting an increasing number of ICH metrics was significantly associated with lower arterial stiffness [lower PWV of the trunk (ß = -0.02 ±0.01; p = 0.004) and AIx (ß = -2.2 ±0.66; p = 0.001), and increased BrachD (ß = 0.14 ±0.07; p = 0.04)]. CONCLUSIONS: Increasing number of ICH metrics was significantly associated with decreased arterial stiffness, but prevalence of ICH in this population was low. Youth with type 1 diabetes could benefit from improvements in their cardiovascular health.
Subject(s)
Adolescent Behavior , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 1/therapy , Diabetic Angiopathies/prevention & control , Diabetic Cardiomyopathies/prevention & control , Health Promotion , Patient Compliance , Adolescent , American Heart Association , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Colorado/epidemiology , Combined Modality Therapy , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/epidemiology , Diabetic Cardiomyopathies/epidemiology , Female , Humans , Hyperglycemia/epidemiology , Hyperglycemia/prevention & control , Longitudinal Studies , Male , Motor Activity , Nutrition Policy , Ohio/epidemiology , Prevalence , Risk Factors , United States/epidemiologyABSTRACT
Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.
Subject(s)
Alleles , Berylliosis/immunology , Beryllium/chemistry , HLA-DP beta-Chains/chemistry , Amino Acid Substitution/drug effects , Amino Acid Substitution/genetics , Amino Acid Substitution/immunology , Berylliosis/genetics , Berylliosis/pathology , Beryllium/adverse effects , Case-Control Studies , Chronic Disease , Female , HLA-DP beta-Chains/genetics , Humans , Inflammation Mediators/adverse effects , Inflammation Mediators/chemistry , Male , Polymorphism, Genetic/immunology , Protein Binding/drug effects , Protein Binding/genetics , Protein Binding/immunology , Respiratory Hypersensitivity/genetics , Respiratory Hypersensitivity/immunology , Respiratory Hypersensitivity/pathology , Static ElectricityABSTRACT
OBJECTIVE: With high prevalence of obesity and overlapping features between diabetes subtypes, accurately classifying youth-onset diabetes can be challenging. We aimed to develop prediction models that, using characteristics available at diabetes diagnosis, can identify youth who will retain endogenous insulin secretion at levels consistent with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We studied 2,966 youth with diabetes in the prospective SEARCH for Diabetes in Youth study (diagnosis age ≤19 years) to develop prediction models to identify participants with fasting C-peptide ≥250 pmol/L (≥0.75 ng/mL) after >3 years' (median 74 months) diabetes duration. Models included clinical measures at the baseline visit, at a mean diabetes duration of 11 months (age, BMI, sex, waist circumference, HDL cholesterol), with and without islet autoantibodies (GADA, IA-2A) and a Type 1 Diabetes Genetic Risk Score (T1DGRS). RESULTS: Models using routine clinical measures with or without autoantibodies and T1DGRS were highly accurate in identifying participants with C-peptide ≥0.75 ng/mL (17% of participants; 2.3% and 53% of those with and without positive autoantibodies) (area under the receiver operating characteristic curve [AUCROC] 0.95-0.98). In internal validation, optimism was very low, with excellent calibration (slope 0.995-0.999). Models retained high performance for predicting retained C-peptide in older youth with obesity (AUCROC 0.88-0.96) and in subgroups defined by self-reported race/ethnicity (AUCROC 0.88-0.97), autoantibody status (AUCROC 0.87-0.96), and clinically diagnosed diabetes types (AUCROC 0.81-0.92). CONCLUSIONS: Prediction models combining routine clinical measures at diabetes diagnosis, with or without islet autoantibodies or T1DGRS, can accurately identify youth with diabetes who maintain endogenous insulin secretion in the range associated with T2D.
ABSTRACT
CONTEXT: Previous studies have shown that exposure to maternal gestational diabetes mellitus (GDM) is associated with increased offspring body mass index (BMI) and risk for overweight or obesity. OBJECTIVE: This study aimed to explore differences in BMI trajectories among youth exposed or not exposed to maternal GDM and understand whether these associations differ across life stages. METHODS: Data from 403 mother/child dyads (76 exposed; 327 not exposed) participating in the longitudinal Exploring Perinatal Outcomes among Children (EPOCH) study in Colorado were used. Participants who had 2 or more longitudinal height measurements from 27 months to a maximum of 19 years were included in the analysis. Life stages were defined using puberty related timepoints: early childhood (27 months to pre-adolescent dip [PAD, average age 5.5 years]), middle childhood (from PAD to age at peak height velocity [APHV, average age 12.2 years]), and adolescence (from APHV to 19 years). Separate general linear mixed models, stratified by life stage, were used to assess associations between GDM exposure and offspring BMI. RESULTS: There was not a significant association between exposure to GDM and BMI trajectories during early childhood (P = .27). In middle childhood, participants exposed to GDM had higher BMI trajectories compared to those not exposed (males: P = .005, females: P = .002) and adolescent (P = .02) periods. CONCLUSION: Our study indicates that children who are exposed to GDM may experience higher BMI trajectories during middle childhood and adolescence, but not during early childhood. These data suggest that efforts to prevent childhood obesity among those exposed in utero to maternal GDM should start before pubertal onset.
Subject(s)
Diabetes, Gestational , Pediatric Obesity , Pregnancy , Male , Female , Child , Adolescent , Humans , Child, Preschool , Diabetes, Gestational/epidemiology , Body Mass Index , Risk Factors , Pediatric Obesity/epidemiology , Pediatric Obesity/etiology , Prospective StudiesABSTRACT
Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Sexual and Gender Minorities , Adult , Adolescent , Humans , Child , Female , Male , Healthcare Disparities , Ethnicity , Gender Identity , Minority Groups , Sexual Behavior , Obesity/epidemiology , Obesity/therapyABSTRACT
Importance: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD. Objective: To investigate the association between metformin use and age-related macular degeneration (AMD). Design, Setting, and Participants: The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022. Interventions: Participants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo. Main Outcomes and Measures: Prevalence of AMD in the treatment arms. Results: Of 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02). Conclusions and Relevance: These data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.
Subject(s)
Diabetes Mellitus, Type 2 , Macular Degeneration , Metformin , Humans , Male , Child , Female , Retrospective Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Metformin/therapeutic use , Cross-Sectional Studies , Macular Degeneration/epidemiology , Macular Degeneration/prevention & control , Macular Degeneration/etiologyABSTRACT
We aimed first to assess associations between maternal health characteristics and newborn metabolite concentrations and second to assess associations between metabolites associated with maternal health characteristics and child body mass index (BMI). This study included 3492 infants enrolled in three birth cohorts with linked newborn screening metabolic data. Maternal health characteristics were ascertained from questionnaires, birth certificates, and medical records. Child BMI was ascertained from medical records and study visits. We used multivariate analysis of variance, followed by multivariable linear/proportional odds regression, to determine maternal health characteristic-newborn metabolite associations. Significant associations were found in discovery and replication cohorts of higher pre-pregnancy BMI with increased C0 and higher maternal age at delivery with increased C2 (C0: discovery: aß 0.05 [95% CI 0.03, 0.07]; replication: aß 0.04 [95% CI 0.006, 0.06]; C2: discovery: aß 0.04 [95% CI 0.003, 0.08]; replication: aß 0.04 [95% CI 0.02, 0.07]). Social Vulnerability Index, insurance, and residence were also associated with metabolite concentrations in a discovery cohort. Associations between metabolites associated with maternal health characteristics and child BMI were modified from 1-3 years (interaction: p < 0.05). These findings may provide insights on potential biologic pathways through which maternal health characteristics may impact fetal metabolic programming and child growth patterns.
ABSTRACT
Objective: With the high prevalence of pediatric obesity and overlapping features between diabetes subtypes, accurately classifying youth-onset diabetes can be challenging. We aimed to develop prediction models that, using characteristics available at diabetes diagnosis, can identify youth who will retain endogenous insulin secretion at levels consistent with type 2 diabetes (T2D). Methods: We studied 2,966 youth with diabetes in the prospective SEARCH study (diagnosis age ≤19 years) to develop prediction models to identify participants with fasting c-peptide ≥250 pmol/L (≥0.75ng/ml) after >3 years (median 74 months) of diabetes duration. Models included clinical measures at baseline visit, at a mean diabetes duration of 11 months (age, BMI, sex, waist circumference, HDL-C), with and without islet autoantibodies (GADA, IA-2A) and a Type 1 Diabetes Genetic Risk Score (T1DGRS). Results: Models using routine clinical measures with or without autoantibodies and T1DGRS were highly accurate in identifying participants with c-peptide ≥0.75 ng/ml (17% of participants; 2.3% and 53% of those with and without positive autoantibodies) (area under receiver operator curve [AUCROC] 0.95-0.98). In internal validation, optimism was very low, with excellent calibration (slope=0.995-0.999). Models retained high performance for predicting retained c-peptide in older youth with obesity (AUCROC 0.88-0.96), and in subgroups defined by self-reported race/ethnicity (AUCROC 0.88-0.97), autoantibody status (AUCROC 0.87-0.96), and clinically diagnosed diabetes types (AUCROC 0.81-0.92). Conclusion: Prediction models combining routine clinical measures at diabetes diagnosis, with or without islet autoantibodies or T1DGRS, can accurately identify youth with diabetes who maintain endogenous insulin secretion in the range associated with type 2 diabetes.
ABSTRACT
INTRODUCTION: Despite widespread recognition among public health experts that childhood sugar-sweetened beverage consumption should be reduced, doing so has proven to be a challenge. An agent-based model of early childhood sugar-sweetened beverage consumption was applied to data from three high-quality, longitudinal cohort studies to gain insight into potentially effective intervention strategies across contexts. METHODS: From 2021 to 2023, a single agent-based model design was applied to data sets derived from three separate cohorts of children followed from infancy to childhood, with very different populations and environments (participants recruited in 1999-2002; 2003-2010; and 2009-2014). After assessing its ability to reproduce observed consumption patterns across cohorts, it was used to simulate potential impacts of multiple intervention strategies across contexts. RESULTS: Interventions reducing home availability of sugar-sweetened beverages consistently had the largest potential effects. Impact differed between cohort settings: a complete decrease in availability resulted in an estimated 87% decrease in overall early childhood consumption for one of the cohorts, compared with 61% and 54% in the others. Reducing availability in center-based child care resulted in substantially greater reduction in one cohort relative to the other two. CONCLUSIONS: There is untapped potential for strategies targeting children's sugar-sweetened beverage consumption in the home, but in some instances, other approaches might also yield meaningful effects. Tailoring approach to setting may be important, and agent-based models can be informative for doing so. This agent-based model has broad generalizability and potential to serve as a tool for designing effective, context-specific strategies to reduce childhood sugar-sweetened beverage consumption.
Subject(s)
Sugar-Sweetened Beverages , Humans , Child, Preschool , Child , Longitudinal Studies , Child Care , Child Health , Public HealthABSTRACT
BACKGROUND: Epigenetic clocks are promising tools for assessing biological age. We assessed the accuracy of pediatric epigenetic clocks in gestational and chronological age determination. RESULTS: Our study used data from seven tissue types on three DNA methylation profiling microarrays and found that the Knight and Bohlin clocks performed similarly for blood cells, while the Lee clock was superior for placental samples. The pediatric-buccal-epigenetic clock performed the best for pediatric buccal samples, while the Horvath clock is recommended for children's blood cell samples. The NeoAge clock stands out for its unique ability to predict post-menstrual age with high correlation with the observed age in infant buccal cell samples. CONCLUSIONS: Our findings provide valuable guidance for future research and development of epigenetic clocks in pediatric samples, enabling more accurate assessments of biological age.
Subject(s)
DNA Methylation , Placenta , Pregnancy , Infant , Humans , Child , Female , Epigenomics , Epigenesis, GeneticABSTRACT
BACKGROUND: Fetal exposure to tobacco increases the risk for many adverse birth outcomes, but whether diet mitigates these risks has yet to be explored. Here, we examined whether maternal folate intake (from foods and supplements) during pregnancy modified the association between prenatal exposure to tobacco and with preterm delivery, small-for-gestational age (SGA) births, or neonatal adiposity. METHODS: Mother-child pairs (n = 701) from Healthy Start were included in this analysis. Urinary cotinine was measured at ~ 27 weeks gestation. Diet was assessed using repeated 24-h dietary recalls. Neonatal adiposity (fat mass percentage) was measured via air displacement plethysmography. Interaction was assessed by including a product term between cotinine (< / ≥ limit of detection [LOD]) and folate (< / ≥ 25th percentile [1077 µg/day]) in separate logistic or linear regression models, adjusting for maternal age, race, ethnicity, education, pre-pregnancy body mass index, and infant sex. RESULTS: Approximately 26% of women had detectable levels of cotinine. Folate intake was significantly lower among women with cotinine ≥ LOD as compared to those with cotinine < LOD (1293 µg/day vs. 1418 µg/day; p = 0.01). Folate modified the association between fetal exposure to tobacco with neonatal adiposity (p for interaction = 0.07) and SGA (p for interaction = 0.07). Among those with lower folate intake, fetal exposure to tobacco was associated with lower neonatal adiposity (mean difference: -2.09%; 95% CI: -3.44, -0.74) and increased SGA risk (OR: 4.99; 95% CI: 1.55, 16.14). Conversely, among those with higher folate intake, there was no difference in neonatal adiposity (mean difference: -0.17%; 95% CI: -1.13, 0.79) or SGA risk (OR: 1.15; 95% CI: 0.57, 2.31). CONCLUSIONS: Increased folate intake during pregnancy (from foods and/or supplements) may mitigate the risk of fetal growth restriction among those who are unable to quit smoking or cannot avoid secondhand smoke during pregnancy.
ABSTRACT
OBJECTIVE: Pediatric positive health refers to children's assessments of their well-being. The purpose of this study was to contrast positive health for children aged 8 to 17 years with and without chronic physical and mental health conditions. METHODS: Data were drawn from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program. Participants included 1764 children ages 8 to 17 years from 13 ECHO cohorts. We measured positive health using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health and Life Satisfaction patient-reported outcome (PRO) measures. We used multiple regression to examine cross-sectional associations between the PROs and parent-reported health conditions and sociodemographic variables. We defined a meaningful difference in average scores as a PROMIS T-score difference of >3. RESULTS: The sample included 45% 13 to 17-year-olds, 50% females, 8% Latinx, and 23% Black/African-American. Fifty-four percent had a chronic health condition. Of the 16 chronic conditions included in the study, only chronic pain (ß = -3.5; 95% CI: -5.2 to -1.9) and depression (ß = -6.6; 95% CI: -8.5 to -4.6) were associated with scoring >3 points lower on global health. Only depression was associated with >3 points lower on life satisfaction (ß = -6.2; 95% CI: -8.1 to -4.3). Among those with depression, 95% also had another chronic condition. CONCLUSIONS: Many children with chronic conditions have similar levels of positive health as counterparts without chronic conditions. The study results suggest that negative associations between chronic conditions and positive health may be primarily attributable to presence or co-occurrence of depression.
Subject(s)
Mental Health , Patient Reported Outcome Measures , Adolescent , Adolescent Health , Child , Chronic Disease , Cross-Sectional Studies , Female , Humans , Male , Quality of LifeABSTRACT
CONTEXT: There is little information about fatty liver in prediabetes as it transitions to early diabetes. OBJECTIVE: This study is aimed at evaluating the prevalence and determinants of fatty liver in the Diabetes Prevention Program (DPP). METHODS: We measured liver fat as liver attenuation (LA) in Hounsfield units (HU) in 1876 participants at ~14 years following randomization into the DPP, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes. LA was compared among intervention groups and in those with versus without diabetes, and associations with baseline and follow-up measurements of anthropometric and metabolic covariates were assessed. RESULTS: There were no differences in liver fat between treatment groups at 14 years of follow-up. Participants with diabetes had lower LA (mean ± SD: 46 ± 16 vs 51 ± 14 HU; P < 0.001) and a greater prevalence of fatty liver (LA < 40 HU) (34% vs 17%; P < 0.001). Severity of metabolic abnormalities at the time of LA evaluation was associated with lower LA categories in a graded manner and more strongly in those with diabetes. Averaged annual fasting insulin (an index of insulin resistance [OR, 95% CI 1.76, 1.41-2.20]) waist circumference (1.63, 1.17-2.26), and triglyceride (1.42, 1.13-1.78), but not glucose, were independently associated with LA < 40 HU prevalence. CONCLUSION: Fatty liver is common in the early phases of diabetes development. The association of LA with insulin resistance, waist circumference, and triglyceride levels emphasizes the importance of these markers for hepatic steatosis in this population and that assessment of hepatic fat in early diabetes development is warranted.
Subject(s)
Biomarkers/blood , Body Mass Index , Diabetes Mellitus, Type 2/epidemiology , Fatty Liver/complications , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Prediabetic State/epidemiology , Aged , Blood Glucose/analysis , Cross-Sectional Studies , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/prevention & control , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Prediabetic State/etiology , Prediabetic State/prevention & control , Prognosis , United States/epidemiologyABSTRACT
CONTEXT: Boys with XXY have greater adiposity and a higher risk of cardiovascular disease. Infants with XXY have lower testosterone concentrations than typical boys, but no studies have evaluated adiposity in infants with XXY or the physiologic effects of giving testosterone replacement. OBJECTIVE: To determine the effect of testosterone on body composition in infants with XXY. DESIGN: Prospective, randomized trial. SETTING: Tertiary care pediatric referral center. PARTICIPANTS: 20 infants 6 to 15 weeks of age with 47,XXY. INTERVENTION: Testosterone cypionate 25 mg intramuscularly monthly for three doses vs no treatment. MAIN OUTCOME MEASURES: Difference in change in adiposity (percent fat mass z scores); other body composition measures, penile length, and safety outcomes between treated and untreated infants; and comparison with typical infants. RESULTS: The increase in percent fat mass (%FM) z scores was greater in the untreated group than in the treated group (+0.92 ± 0.62 vs -0.12 ± 0.65, P = 0.004). Increases in secondary outcomes were greater in the testosterone-treated group for total mass, fat-free mass, length z score, stretched penile length, and growth velocity (P < 0.002 for all). At 5 months of age, adiposity in untreated infants with XXY was 26.7% compared with 23.2% in healthy male infants of the same age (P = 0.0037); there was no difference in %FM between the treated XXY boys and controls. Reported side effects were minimal and self-limited; no serious adverse events occurred. CONCLUSIONS: Adiposity of untreated infants was 15% greater than that of male controls by 5 months of age. Testosterone treatment for infants with XXY resulted in positive changes in body composition.
ABSTRACT
OBJECTIVE: The objective of the study was to assess the prevalence and determinants of elevated apolipoprotein B (apoB) and dense low-density lipoprotein (LDL) in United States youth with type 1 or type 2 diabetes. METHODS: We conducted cross-sectional analyses of apoB concentrations, LDL density, and prevalence of elevated apoB levels and dense LDL from the SEARCH for Diabetes in Youth study, a six-center U.S.-based study of youth with diabetes onset younger than 20 years of age (2657 with type 1 and 345 with type 2). RESULTS: Among youth with type 1 diabetes, 11% had elevated apoB (>or=100 mg/dl, 1.95 mm/liter), 8% had dense LDL (relative flotation rate
Subject(s)
Apolipoproteins B/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Adolescent , Adult , Child , Cross-Sectional Studies , Glycated Hemoglobin/analysis , HumansABSTRACT
BACKGROUND: Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. METHODS: We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ≥ 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the 'high risk autoantibody profile (HRP)' as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. RESULTS: In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1ß in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p = 0.04) and a 26% lower IL-1ß (p = 0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p = 0.0006, p = 0.006, p = 0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations. CONCLUSIONS: Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity warrants further investigation into the potential systemic effects of RA-related autoantibodies and adiponectin on inflammation in the absence of clinically apparent RA.