Background/Objectives: There is increasing interest in and evidence for the role of ultra-processed foods (UPFs) in cardiometabolic risk. We tested the hypothesis that UPF intake score derived from dietary history is associated with measures of insulin secretion and sensitivity in a family setting even when the process of type 2 diabetes is still to ensue. Methods: We used data from our well-characterized San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) study cohort of nondiabetic children (aged 6-17 years). Dietary history was assessed using the Block Food Frequency Questionnaire. Outcomes of interest were 19 clinically useful indexes of insulin secretion/sensitivity based on fasting and oral glucose tolerance test results. Since the SAFARI study employed a family study design, we used polygenic regression models that adjusted for complex interactions between age and sex and accounted for important comorbidities. Results: A total of 53.3% of daily energy intake was contributed by UPF. Of the 19 indexes tested for association with the UPF score, we found a statistically significant association with measures of insulin resistance and beta cell function and with three indexes based on the results of oral glucose tolerance test as follows: Matsuda index (β = -0.0962, p = 0.0262), insulinogenic index at 30 min (β = 0.1779, p = 0.0006) and disposition index at 30 min (β = 0.1538, p = 0.0061). Conclusions: Even in nondiabetic children there was a significant and independent association of UPF intake with insulin secretion and sensitivity. Future studies need to investigate this association in larger, longitudinal settings and in randomized trials controlling potential systematic errors.

Introduction and Objective: Maternal soda intake during pregnancy has been associated with increased health problems in children, including prematurity and overweight/obesity in infancy and childhood. Longer-term effects remain unclear. Our aim was to assess whether maternal soda consumption during pregnancy was associated with increased body mass index (BMI) and impaired glucose tolerance/prediabetes in offspring, including both children and adolescents. Methods: We measured the associations between retrospectively reported maternal intake of sugar-sweetened (SS), diet (DS), and total sodas (TS: the sum of SS + DS) during pregnancy, and cardiometabolic risk in 402 metabolically at-risk Mexican American children and adolescents (6-17 years) from the San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI), a family-based genetic epidemiology study. Covariates included offspring age, sex, pubertal status, and current soda intake; maternal BMI at age 20 and diabetes status; and neighborhood income. Results: SS exposure in utero was associated with elevated 2-hr glucose (2hrG, mg/dl) following an oral glucose tolerance test: β = 1.85 (95% CI: 0.023 to 3.69; p <0.05), and increased prevalence of glucose intolerance/pre-diabetes: odds ratio (OR) = 1.27 (95% CI: 1.05 to 1.52; p=0.01). Gestational DS exposure was associated with increased BMI: β = 5.36 (95% CI: 2.13 to 8.59; p=0.001), waist circumference (mm): β = 104 (95% CI: 21.0 to 186; p=0.01) and 2hrG: β = 15.3 (95% CI: 1.00 to 29.7; p=0.04). TS exposure was associated with increased 2hrG: β = 2.08 (95% CI: 0.242 to 3.91; p=0.03) and glucose intolerance/pre-diabetes prevalence: OR: 1.28 (95% CI: 1.06 to 1.54; p<0.01). Conclusion: These SAFARI findings suggest that gestational soda exposure - whether sugar-sweetened, diet, or total - may have more profound and long-lasting impacts on offspring cardiometabolic risk than have previously been reported. S.P.G. Fowler: None. D. Gimeno: None. R.G. Resendez: None. A. Diaz-Badillo: None. J. Schneider: None. D.E. Hale: None. J.L. Lynch: Research Support; Novo Nordisk, Beta Bionics, Inc, MannKind Corporation. S. Mummidi: None. D.M. Lehman: None. R. Arya: None. R.A. DeFronzo: Advisory Panel; AstraZeneca. Research Support; AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Advisory Panel; Corcept Therapeutics, Novo Nordisk. Speaker's Bureau; Corcept Therapeutics. Research Support; 89bio, Inc, Amgen Inc. J. Blangero: None. R. Duggirala: None. National Institutes of Health (R01 HD049051, HD041111,DK053889, DK042273, K01DK064867, P01 HL045522, DK047482,MH059490, M01-RR-01346, and HD049051-5S1 (ARRA), and a Veterans Administration EpidemiologicGrant.

Early-life exposure to organic chemicals (OCs) may influence childhood obesity and associated cardiometabolic risk. These conditions have been shown to disproportionately affect minority populations such as Mexican Americans (MAs). However, information on the impact of organic chemicals on cardiometabolic risk in MA children is limited. Therefore, we conducted a pilot study to assess the extent to which exposure to organic chemicals influences cardiometabolic traits (CMTs) in MA children. We recalled 25 children from a previous study and collected 25 primary teeth from them. Chemical analyses of the teeth were performed using established protocols. Target analytes included acetaminophen (APAP); 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), diethyl phosphate (DEP), N,N-diethyl-m-toluamide (DEET), tris(2-butoxyethyl) phosphate (TBOEP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The organic chemicals most frequently detected in the teeth were APAP; the insect repellent DEET; plasticizers MnBP and MiBP; and the plasticizer-derived metabolite MEHP. These five analytes were included in association analyses with selected CMTs. After adjusting for covariate (age, sex, tooth-type) effects, we found significant (p < 0.05) positive correlations between MiBP and the following CMTs: fat mass, fasting insulin, and the homeostasis model of assessment-insulin resistance (HOMA-IR). Both MnBP and MEHP exhibited negative correlation with blood pressure measures and triglycerides, respectively. In addition, APAP showed a strong negative correlation with HDL-C (p = 0.009) and positive association with triglycerides (p < 0.10). These findings suggest a potential role for early-life exposures to organic chemicals in influencing cardiometabolic risk in MA children.

Background This paper describes a randomised controlled trial (RCT) protocol aimed at investigating the efficacy of caregivers’ Mind-Mindedness training as an early intervention for preschoolers with social anxiety. Mind-mindedness, a caregiver's ability to recognise and respond to a child as an individual with their own thoughts, feelings, and intentions, is associated with secure attachment and socioemotional skills. While previous studies indicate brief Mind-Mindedness training may increase caregiver mentalisation in high-risk groups, rigorous research on the impacts of social anxiety in children is limited. Building on the well-established link between caregiver’s Mind-Mindedness and positive socioemotional outcomes in children, this study aims to bridge the existing research gap by directly testing the impact of Mind-Mindedness training on social anxiety. Methods This randomized controlled trial aims to recruit 100 caregivers of preschool-aged 4 to 7-year-old children with social anxiety from the UK and Iran. The caregivers will be randomly assigned to either a mind-mindedness training group (n=50) or a peer support (control) group(n=50). The mind-mindedness training will involve three online sessions focused on teaching strategies for using mind-minded comments, the program will consist of three online sessions, each lasting one hour and conducted over three consecutive weeks. The peer support (control) group will have access to a private online peer-support platform for sharing experiences. Measures of mind-mindedness, child social anxiety, attachment, and theory of mind will be assessed at baseline, post-intervention, and 3-month follow-up using established assessment tools. Discussion The study aims to evaluate the effectiveness of a mind-mindedness parental intervention for social anxiety in children and to uncover the potential mediating roles of attachment and theory of mind in the relationship between mind-mindedness and child anxiety. The cross-cultural design, involving participants from the UK and Iran, will offer valuable information on the cultural aspect of the intervention. The training group is hypothesized to lead to increased mind-mindedness and reduced child social anxiety versus a peer support (control) group. This research can establish evidence for mind-mindedness training as an early intervention approach for childhood social anxiety.   Trial registration Prospectively registered on ClinicalTrials.gov (ID: [NCT06657014][1]; registered on 23th October 2024). ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT Number [NCT06657014][1] Iranian Registry of Clinical Trials (IRCT) ID: 80088 ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Name of IRB/Ethics Committee: Social Sciences Ethics Committee Approval Number: 2024-8579-12232 Approval Statement: This study was approved by the Social Sciences Ethics Committee (Approval No: 2024-8579-12232) on 26/08/2024. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files. Receutment has not started yet. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06657014&atom=%2Fmedrxiv%2Fearly%2F2024%2F11%2F26%2F2024.11.23.24317842.atom

Siblings of individuals with disabilities hold a pivotal and sometimes unappreciated position in the lives of their brother or sister. We sought to understand the unique challenges and opportunities in relationships between children with chromosome 18 conditions and their siblings and to identify the ways to support this relationship. Participants were recruited through the lay advocacy organization, the Chromosome 18 Registry & Research Society. Fifty-seven siblings from 36 families participated, using an investigator designed instrument, were asked to agree or disagreed with statements from four content areas (information and knowledge about the syndrome, feelings about the sibling relationship, involvement with and caregiving for their sibling, and support and advocacy). Siblings reported that they know their sibling with a disability very well and reported a wide range of emotions regarding their sibling. There was a strong sense of pride in their brother/sister's abilities, and many participants reported attempts to help others understand their brother/sister. Many siblings reported a dislike for the common assumption that their affected sibling is a burden on the family. Most participants reported feeling some degree of responsibility for their affected sibling, but many also reported that they enjoy this role. Sixty-three parents from 36 families responded to the survey. Most parents felt their typically developing children enjoyed teaching new things to their affected child as well as being a good role model for them. Most parents also felt their typically developing child was comfortable telling others about their sibling's condition. Recommendations for interventions and future research are discussed.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h 2 = 0.98, P = 7 × 10 –18 and h 2 = 0.58, P = 1 × 10 –7 ]. We found significant ( P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (− 0.22), waist circumference (− 0.25), triglycerides (− 0.18), fat mass (− 0.23), fasting glucose (− 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (− 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Background Self-management of type 1 diabetes (T1D) requires numerous decisions and actions by people with T1D and their caregivers and poses many daily challenges. For those with T1D and a developmental disorder such as autism spectrum disorder (ASD), more complex challenges arise, though these remain largely unstudied. Objective This study aimed to better understand the barriers and facilitators of raising a child with T1D and ASD. Secondary analysis of web-based content (phase 1) and telephone interviews (phase 2) were conducted to further expand the existing knowledge on the challenges and successes faced by these families. Methods Phase 1 involved a qualitative analysis of publicly available online forums and blog posts by caregivers of children with both T1D and ASD. Themes from phase 1 were used to create an interview guide for further in-depth exploration via interviews. In phase 2, caregivers of children with both T1D and ASD were recruited from Penn State Health endocrinology clinics and through the web from social media posts to T1D-focused groups and sites. Interested respondents were directed to a secure web-based eligibility assessment. Information related to T1D and ASD diagnosis, contact information, and demographics were collected. On the basis of survey responses, participants were selected for a follow-up telephone interview and were asked to complete the adaptive behavior assessment system, third edition parent form to assess autism severity and upload a copy of their child’s most recent hemoglobin A1c (HbA1c) result. Interviews were transcribed, imported into NVivo qualitative data management software, and analyzed to determine common themes related to barriers and facilitators of raising a child with both ASD and T1D. Results For phase 1, 398 forum posts and blog posts between 2009 and 2016 were analyzed. Common themes related to a lack of understanding by the separate ASD and T1D caregiver communities, advice on coping techniques, rules and routines, and descriptions of the health care experience. For phase 2, 12 eligible respondents were interviewed. For interviewees, the average age of the child at diagnosis with T1D and ASD was 7.92 years and 5.55 years, respectively. Average self-reported and documented HbA1c levels for children with T1D and ASD were 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol), respectively. Common themes from the interviews related to increased emotional burden, frustration surrounding the amount of information they are expected to learn, and challenges in the school setting. Conclusions Caregivers of children with both T1D and ASD face unique challenges, distinct from those faced by caregivers of individuals who have either disorder alone. Understanding these challenges may help health care providers in caring for this unique population. Referral to the diabetes online community may be a potential resource to supplement the care received by the medical community.

Metacognitive skills have been shown to be strongly associated with academic achievement and serve as the basis of many therapeutic treatments for mental health conditions. Thus, it is likely that training metacognitive skills can lead to improved academic skills and health and well-being. Because metacognition is an awareness of one’s own thoughts, and as such is not directly observable, it is often measured by self-report. This study reviews and critiques the use of self-report in evaluating metacognition by conducting systematic reviews and a meta-analysis of studies assessing metacognitive skills. Keyword searches were performed in EbscoHost, ERIC, PsycINFO, PsycArticles, Scopus, Web of Science, and WorldWideScience.org to locate all articles evaluating metacognition through self-report. 24,396 articles from 1982 through 2018 were screened for inclusion in the study. Firstly, a systematic review of twenty-two articles was conducted to review the ability of self-report measures to evaluate a proposed taxonomy of metacognition. Secondly, a systematic review and meta-analyses of 37 studies summarizes the ability of self-report to relate to metacognitive behavior and the possible effects of differences in research methods. Results suggest that self-reports provide a useful overview of two factors – metacognitive knowledge and metacognitive regulation. However, metacognitive processes as measured by self-report subscales are unclear. Conversely, the two factors of metacognition do not adequately relate to metacognitive behavior, but subscales strongly correlate across self-reports and metacognitive tasks. Future research should carefully consider the role of self-reports when designing research evaluating metacognition.

AIM:Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs).METHODS:We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes.RESULTS:Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI→HOMA-IR→AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q.CONCLUSION:Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.

We have recently reported that serum concentrations of α-carotene (AC) and β-carotene (BC) are under strong genetic influences and were correlated with obesity and other cardio-metabolic traits in Mexican American (MA) children. Our previously developed Pediatric Metabolic Index (PMI) correlates with insulin resistance (IR) after adjusting for age and sex using lipid and adiposity data from Mexican children. A PMI score > 2.0 predicts metabolic abnormalities including IR (i.e., HOMA-IR). Yet data on other MA children with PMI > 2 with normal IR and PMI < 2 with high IR, suggest a role for additional factors in determining insulin sensitivity (IS). In this study, we aimed to assess interactions between carotenoids and the PMI in predicting IS as measured by Matsuda index using the surface-response analysis (SRA). Four different carotenoids, namely, AC, BC, lycopene (Lyc), and β-cryptoxanthin (CX) from ∼590 children enrolled in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) study were measured by mass spectrometry. Glucose and insulin levels were measured after oral glucose tolerance test and IS index (ISI) was calculated using Matsuda method. SRA was used to determine two-way interactions of serum carotenoids and PMI on ISI. The computer programs SOLAR and STATISTICA 7.0 were used for statistical analysis. The SRA showed an increase in ISI in children with PMI scores between 2 to 4. This effect was modified in the presence of lower serum AC and BC levels; and, interactions between these two carotenoids and PMI had maximal effect on ISI. Conversely, MA children with moderate PMI scores can have substantial improvement in their IS with higher serum AC and BC levels. In contrast, there was a minimal surface response to Lyc and CX serum levels. Notably, despite an optimal PMI, children with lower concentrations of AC and BC showed less IS. In summary, we found that interactions between carotenoids with PMI may predict IS in MA children. Disclosure S. Mummidi: None. J. Hernandez-Ruiz: None. V.S. Farook: None. L. Reddivari: None. A. Diaz-Badillo: None. S.P. Fowler: None. R.G. Resendez: None. F. Akhtar: None. D. Lehman: None. C. Jenkinson: None. R. Arya: None. J.L. Lynch: Board Member; Self; American Academy of Pediatrics. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Daiichi Sankyo Company, Limited, National Institutes of Health, Novo Nordisk Inc., Pediatric Diabetes Consortium. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. D.E. Hale: None. J. Blangero: None. J.C. Lopez-Alvarenga: None. R. Duggirala: None. J.K. Vanamala: None. Funding National Institutes of Health (R01HD049051, R01AI119131, HD049051-5S1, HD041111, DK053889, DK042273, DK047482, P01HL45522, MH59490, M01-RR-01346), U.S. Department of Veterans Affairs; Max and Minnie Tomerlin Voelcker Fund; National Institute of Food and Agriculture (2009-55200-05197)

Tetrasomy 18p is a rare chromosomal abnormality, resulting from an additional iso-chromosome composed of two copies of the short arm. It is characterized by craniofacial abnormalities, neuromuscular dysfunction, and developmental delay. The Chromosome 18 Clinical Research Center has established the largest cohort of individuals with this rare genetic condition. Here, we describe a case series of 21 individuals with tetrasomy 18p who have a previously unreported clinical finding: low bone mineral density. Most individuals met criteria for low bone density despite being relatively young (mean age of 21 years). Clinicians providing care to individuals affected by Tetrasomy 18p should be aware of their increased risk for decreased bone density and pathological fractures.

Abstract Purpose International guidance on health-care transition has existed for over a decade; however, many unanswered questions remain. This systematic review of reviews aimed to answer the question: is a later age of transfer from pediatric to adult health care associated with improved health and health service outcomes? Methods We included systematic reviews which considered at least one long-term condition and provided outcome data from adult services. Methodology of primary studies was not an exclusion criterion. We searched multiple databases and conducted an initial search in May 2015 which was repeated in May 2017. All reviews were assessed for quality using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) tool. Reviews that scored less than 22 were excluded. Results Initial searches identified 6,149 papers. Forty-three reviews met exclusion and inclusion criteria, and 15 reviews also met quality criteria. With one exception, primary studies from reviews which only considered quantitative evidence found that a delayed age of transfer resulted in improved outcomes. Qualitative and mixed-methods evidence supported the view that age 18 was an appropriate time of transfer. Conclusion We found moderate evidence that models of transition which transfer young people in late adolescence or early adulthood can improve transition outcomes and patient satisfaction.

BackgroundThe Chromosome 18 Clinical Research Center has created a pediatrician-friendly virtual resource center for managing patients with chromosome 18 abnormalities. To date, children with rare chromosome abnormalities have been cared for either symptomatically or palliatively as a reaction to the presenting medical problems. As we enter an era of genomic-informed medicine, we can provide children, even those with individually unique chromosome abnormalities, with proactive medical care and management based on the most contemporary data on their specific genomic change. It is problematic for practicing physicians to obtain and use the emerging data on specific genes because this information is derived from diverse sources (e.g., animal studies, case reports, invitro explorations) and is often published in sources that are not easily accessible in the clinical setting. MethodsThe Chromosome 18 Clinical Resource Center remedies this challenging problem by curating and synthesizing the data with clinical implications. The data are collected from our database of over 26years of natural history and medical data from over 650 individuals with chromosome 18 abnormalities. ResultsThe resulting management guides and video presentations are a first edition of this collated data specifically oriented to guide clinicians toward the optimization of care for each child. ConclusionThe chromosome 18 data and guides also serve as models for an approach to the management of any individual with a rare chromosome abnormality of which there are over 1,300 born every year in the US alone.

Children with both T1D and autism pose a distinct challenge, and there is exceedingly little research on T1D self-management in this special population and few resources to guide healthcare providers (HCPs) on how to best partner with families. This qualitative study used an exploratory inductive thematic approach to analyze a public Internet forum authored by caregivers to children with both T1D and autism. All 398 posts were imported into NVivo 11 (QSR International). After codebook development, the primary coders (TO, SO) coded 10% and then 20% of the dataset, with Cohen’s kappa .994 and .996, respectively. With high inter-rater reliability established, coding of all remaining posts was then completed. Inductive thematic analysis revealed the following themes: 1) Parents of children with T1D and autism yearned for support and did not feel understood by the autism community or the T1D community; social media provided much-needed peer support from families that understood the unique experience of raising a child with both conditions. 2) Numerous coping techniques were discussed, including focusing on T1D management first, as glucose levels could affect behavior; establishing concrete rules and routines; and advice on types of needles and technology that might be better tolerated in this unique population. 3) Descriptions of the healthcare experience, including the helpfulness of multidisciplinary teams with endocrinologists and autism specialists jointly developing treatment plans. 4) Challenges in school and camp settings, as well as challenges in finding caregivers. 5) Sensory issues precluding use of technology such as insulin pumps, and the utility of tubeless pumps in overcoming some of these challenges. This study provides valuable insight for HCPs into the challenges these families face and lays the groundwork for future studies to evaluate how HCPs can best care for and advise this unique population. Disclosure T. Oser: None. S.M. Oser: None. K. Bangalore Krishna: None. D.E. Hale: None.

There is increasing evidence that youth who follow the early onset persistent (EOP), adolescent-onset (AO) and childhood-limited (CL) trajectories of conduct problems show varying patterns of health, mental health, educational, and social outcomes in adulthood. However, there has been no systematic review and meta-analysis on outcomes associated with different conduct problems trajectories. We systematically reviewed the literature of longitudinal studies considering outcomes of three conduct problems trajectories: EOP, AO, and CL compared with individuals with low levels of conduct problems (low). We performed a series of meta-analyses comparing each trajectory to the low group for eight different outcomes in early adulthood or later. Thirteen studies met our inclusion criteria. Outcomes were mental health (depression), cannabis use, alcohol use, self-reported aggression, official records of antisocial behaviour, poor general health, poor education, and poor employment. Overall, EOP individuals showed significant higher risk of poor outcome followed by AO individuals, CL individuals, and finally participants in the low group. All conduct problems trajectories showed higher risk of poor psychosocial outcomes compared to the low group, but the magnitude of risk differed across trajectories, with a general trend for the EOP to perform significantly worse, followed by the AO and CL. Early intervention is recommended across domains to maximise likelihood of desistance from antisocial behaviour and improvement on several psychosocial outcomes.

In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chromosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.

ABSTRACTKnowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited. The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6–17 years). The environments examined were sedentary activity (SA), assessed by recalls from “yesterday” (SAy) and “usually” (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment—insulin resistance (HOMA‐IR), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood‐based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA‐IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA‐IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.

AimsWe aimed to determine the prevalence of arterial stiffness in young adults with youth-onset type 2 diabetes who previously participated in the TODAY clinical trial and whether arterial stiffness is influenced by their prior diabetes treatment assignment or glycemic control.MethodsWe measured arterial stiffness by femoral, radial, and foot pulse wave velocity (PWV), augmentation index (AIx), and brachial distensibility (BrachD) in 453 TODAY participants (age 20.8 ± 2.5 years, diabetes duration 7.6 ± 1.5 years, 36.4% male, BMI 36.7 ± 8.2 kg/m2) at a mean of 7.6 years post-randomization. Increased arterial stiffness in TODAY youth was defined compared with data from lean controls. We assessed whether glycemic control over time or diabetes treatment in TODAY was associated with arterial stiffness.ResultsArterial stiffness was identified in up to 50% of TODAY participants. Prior diabetes treatment assignment was not associated with higher arterial stiffness. Glycemic control over time was associated with PWV radial and foot only. Age, race-ethnicity, sex, higher blood pressure and BMI were also associated with higher arterial stiffness.ConclusionsNearly half of TODAY youth have increased arterial stiffness. Targeting blood pressure and perhaps obesity and glycemic control may positively impact arterial health in adolescents with type 2 diabetes.Trial registration: ClinicalTrials.gov NCT00081328.