Celiac Disease and Pediatric Type 1 Diabetes: Diagnostic and Treatment Dilemmas

Despite the advent of sensitive and specific serologic testing, routine screening for celiac disease (CD) in diabetic populations may not be universal practice, and many clinicians struggle to find the optimal approach to managing CD in pediatric Type 1 diabetes (T1D) patients. While some clinicians advocate screening for CD in all patients with T1D, others are unsure whether this is warranted. The diagnosis of patients who present with symptomatic CD, including malabsorption and obvious pathology upon biopsy, remains straightforward, with improvements noted on a gluten-free diet. Many patients identified by screening, however, tend to be asymptomatic. Evidence is inconclusive as to whether the benefits of screening and potentially treating asymptomatic individuals outweigh the harms of managing a population already burdened with a serious illness. This review focuses on current knowledge of CD in children and youth with T1D, highlighting important elements of the disease's pathophysiology, epidemiology, clinical presentation, and diagnostic challenges

Gender diversity is correlated with dimensional neurodivergent traits but not categorical neurodevelopmental diagnoses in children

Background: Gender clinic and single‐item questionnaire‐based data report increased co‐occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under‐studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. Methods: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4–12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi‐dimensionally using a well‐validated parent‐report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex‐assigned‐at‐birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. Results: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC‐derived scores. Instead, higher early‐childhood dimensional autistic social‐communication traits correlated with higher current overall gender incongruence (as defined by GIQC‐14 score). This correlation was potentially moderated by sex‐assigned‐at‐birth: greater early‐childhood autistic social‐communication traits were associated with higher current overall gender incongruence in assigned‐males‐at‐birth, but not assigned‐females‐at‐birth. For fine‐grained gender diversity domains, greater autistic restricted‐repetitive behavior traits were associated with greater diversity in gender identity across sexes‐assigned‐at‐birth; greater autistic social‐communication traits were associated with lower stereotypical male expression across sexes‐assigned‐at‐birth. Conclusions: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early‐childhood autistic social‐communication traits and overall current gender diversity was most evident in assigned‐males‐at‐birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender‐diverse populations

A Dominant X-Linked QTL Regulating Pubertal Timing in Mice Found by Whole Genome Scanning and Modified Interval-Specific Congenic Strain Analysis

BACKGROUND: Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which differed significantly in the pubertal timing. Vaginal opening (VO) was used to characterize pubertal timing in female mice, and the age at VO of all female mice (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the F1 intercrosses to identify quantitative trait loci (QTLs) controlling this trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM, LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL contributed 2.1 days to the timing of VO, which accounted for 32.31% of the difference between the original strains. Further study showed that the QTL was B6-dominant and explained 10.5% of variation to this trait with a power of 99.4% at an alpha level of 0.05.The location of the significant ChrX QTL found by genome scanning was then fine-mapped to a region of approximately 2.5 cM between marker DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified interval-specific congenic strains (mISCSs). CONCLUSIONS/SIGNIFICANCE: Such findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty, and also reveal the fact that chromosome X (the sex chromosome) does carry gene(s) which take part in the regulative pathway of the pubertal timing in mice

The Impact of Telemedicine Interventions Involving Routine Transmission of Blood Glucose Data with Clinician Feedback on Metabolic Control in Youth with Type 1 Diabetes: A Systematic Review and Meta-Analysis

Abstract Our objective was to determine the impact of telemedicine (TM) interventions on the management of type 1 diabetes (T1DM) in youth. We performed a systematic review of randomized trials that evaluated TM interventions involving transmission of blood glucose data followed by unsolicited scheduled clinician feedback. We found no apparent effect of the TM interventions on hemoglobin A1c (HbA1c), severe hypoglycemia, or diabetic ketoacidosis. The limited data available on patient satisfaction, quality of life, and cost also suggested no differences between groups. It is unlikely that TM interventions, as performed in the assessed studies, had a substantial effect on glycemic control or acute complications. However, it remains possible that there are other benefits of TM not adequately reported, that newer TM strategies may be more effective and that interventions may benefit subgroups of youth, such as those with the poor glycemic control, adolescents, or those living in remote areas