Nutrient Timing in Resistance-Trained Women

The purpose of this study was to evaluate the effects of different peri-workout nutrition strategies on strength, body composition, and metabolism in trained females. Young, trained females (n=43) completed body composition and strength testing before and after training. Participants were randomized into three groups using baseline leg press strength; pre-exercise supplementation of a protein-carbohydrate shake (PRE), post-exercise supplementation (POST), or a control group (CON). Following baseline testing, participants were trained twice per week for six weeks using high intensity resistance training. At the first and last training, metabolic testing was completed before and after exercise. There were significant main effects for time for LM (p=0.003) and %fat (p0.05). These results demonstrate that peri-workout nutrition is potentially important for body composition, but either a PRE or POST strategy is effective.Master of Art

The dose–response effect of insulin sensitivity on albuminuria in children according to diabetes type

Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose-response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases

Defects in IL-2R Signaling Contribute to Diminished Maintenance of FOXP3 Expression in CD4+CD25+ Regulatory T-Cells of Type 1 Diabetic Subjects

OBJECTIVE In humans, multiple genes in the interleukin (IL)-2/IL-2 receptor (IL-2R) pathway are associated with type 1 diabetes. However, no link between IL-2 responsiveness and CD4+CD25+FOXP3+ regulatory T-cells (Tregs) has been demonstrated in type 1 diabetic subjects despite the role of these IL-2–dependent cells in controlling autoimmunity. Here, we address whether altered IL-2 responsiveness impacts persistence of FOXP3 expression in Tregs of type 1 diabetic subjects. RESEARCH DESIGN AND METHODS Persistence of Tregs was assessed by culturing sorted CD4+CD25hi natural Tregs with IL-2 and measuring FOXP3 expression over time by flow cytometry for control and type 1 diabetic populations. The effects of IL-2 on FOXP3 induction were assessed 48 h after activation of CD4+CD25− T-cells with anti-CD3 antibody. Cytokine receptor expression and signaling upon exposure to IL-2, IL-7, and IL-15 were determined by flow cytometry and Western blot analysis. RESULTS Maintenance of FOXP3 expression in CD4+CD25+ Tregs of type 1 diabetic subjects was diminished in the presence of IL-2, but not IL-7. Impaired responsiveness was not linked to altered expression of the IL-2R complex. Instead, IL-2R signaling was reduced in Tregs and total CD4+ T-cells of type 1 diabetic subjects. In some individuals, decreased signal transducer and activator of transcription 5 phosphorylation correlated with significantly higher expression of protein tyrosine phosphatase N2, a negative regulator of IL-2R signaling. CONCLUSIONS Aberrant IL-2R signaling in CD4+ T-cells of type 1 diabetic subjects contributes to decreased persistence of FOXP3 expression that may impact establishment of tolerance. These findings suggest novel targets for treatment of type 1 diabetes within the IL-2R pathway and suggest that an altered IL-2R signaling signature may be a biomarker for type 1 diabetes

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012

Diagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001–2009 period, but data on recent incidence trends are lacking

Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study

The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment

Corticotropin-releasing hormone as the homeostatic rheostat of feto-maternal symbiosis and developmental programming In utero and neonatal life

A balanced interaction between the homeostatic mechanisms of mother and the devel- oping organism during pregnancy and in early neonatal life is essential in order to ensure optimal fetal development, ability to respond to various external and internal challenges, protection from adverse programming, and safeguard maternal care availability after parturition. In the majority of pregnancies, this relationship is highly effective resulting in successful outcomes. However, in a number of pathological settings, perturbations of the maternal homeostasis disrupt this symbiosis and initiate adaptive responses with unpre- dictable outcomes for the fetus or even the neonate. This may lead to development of pathological phenotypes arising from developmental reprogramming involving interaction of genetic, epigenetic, and environmental-driven pathways, sometimes with acute conse- quences (e.g., growth impairment) and sometimes delayed (e.g., enhanced susceptibility to disease) that last well into adulthood. Most of these adaptive mechanisms are activated and controlled by hormones of the hypothalamo-pituitary adrenal axis under the influ- ence of placental steroid and peptide hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone (CRH) plays a key role in feto-maternal communication by orchestrating and integrating a series of neuroendocrine, immune, metabolic, and behavioral responses. CRH also regulates neural networks involved in maternal behavior and this determines efficiency of maternal care and neonate interactions. This review will summarize our current understanding of CRH actions during the perinatal period, focusing on the physiological roles for both mother and offspring and also how external challenges can alter CRH actions and potentially impact on fetus/neonate health

Characterizing the weight-glycemia phenotypes of type 1 diabetes in youth and young adulthood

Introduction Individuals with type 1 diabetes (T1D) present with diverse body weight status and degrees of glycemic control, which may warrant different treatment approaches. We sought to identify subgroups sharing phenotypes based on both weight and glycemia and compare characteristics across subgroups. Research design and methods Participants: with T1D in the SEARCH study cohort (n=1817, 6.0-30.4 years) were seen at a follow-up visit >5 years after diagnosis. Hierarchical agglomerative clustering was used to group participants based on five measures summarizing the joint distribution of body mass index z-score (BMIz) and hemoglobin A1c (HbA1c) which were estimated by reinforcement learning tree predictions from 28 covariates. Interpretation of cluster weight status and glycemic control was based on mean BMIz and HbA1c, respectively. Results: The sample was 49.5% female and 55.5% non-Hispanic white (NHW); mean±SD age=17.6±4.5 years, T1D duration=7.8±1.9 years, BMIz=0.61±0.94, and HbA1c=76±21 mmol/mol (9.1±1.9)%. Six weight-glycemia clusters were identified, including four normal weight, one overweight, and one subgroup with obesity. No cluster had a mean HbA1c <58 mmol/mol (7.5%). Cluster 1 (34.0%) was normal weight with the lowest HbA1c and comprised 85% NHW participants with the highest socioeconomic position, insulin pump use, dietary quality, and physical activity. Subgroups with very poor glycemic control (ie, ≥108 mmol/mol (≥12.0%); cluster 4, 4.4%, and cluster 5, 7.5%) and obesity (cluster 6, 15.4%) had a lower proportion of NHW youth, lower socioeconomic position, and reported decreased pump use and poorer health behaviors (overall p<0.01). The overweight subgroup with very poor glycemic control (cluster 5) showed the highest lipids and blood pressure (p<0.01). Conclusions: There are distinct subgroups of youth and young adults with T1D that share weight-glycemia phenotypes. Subgroups may benefit from tailored interventions addressing differences in clinical care, health behaviors, and underlying health inequity. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Inflammation and acute traffic-related air pollution exposures among a cohort of youth with type 1 diabetes

Background: Evidence remains equivocal regarding the association of inflammation, a precursor to cardiovascular disease, and acute exposures to ambient air pollution from traffic-related particulate matter. Though youth with type 1 diabetes are at higher risk for cardiovascular disease, the relationship of inflammation and ambient air pollution exposures in this population has received little attention. Objectives: Using five geographically diverse US sites from the racially- and ethnically-diverse SEARCH for Diabetes in Youth Cohort, we examined the relationship of acute exposures to PM2.5 mass, Atmospheric Dispersion Modeling System (ADMS)-Roads traffic-related PM concentrations near roadways, and elemental carbon (EC) with biomarkers of inflammation including interleukin-6 (IL-6), c-reactive protein (hs-CRP) and fibrinogen. Methods: Baseline questionnaires and blood were obtained at a study visit. Using a spatio-temporal modeling approach, pollutant exposures for 7 days prior to blood draw were assigned to residential addresses. Linear mixed models for each outcome and exposure were adjusted for demographic and lifestyle factors identified a priori. Results: Among the 2566 participants with complete data, fully-adjusted models showed positive associations of EC average week exposures with IL-6 and hs-CRP, and PM2.5 mass exposures on lag day 3 with IL-6 levels. Comparing the 25th and 75th percentiles of average week EC exposures resulted in 8.3% higher IL-6 (95%CI: 2.7%,14.3%) and 9.8% higher hs-CRP (95%CI: 2.4%,17.7%). We observed some evidence of effect modification for the relationships of PM2.5 mass exposures with hs-CRP by gender and with IL-6 by race/ethnicity. Conclusions: Indicators of inflammation were associated with estimated traffic-related air pollutant exposures in this study population of youth with type 1 diabetes. Thus youth with type 1 diabetes may be at increased risk of air pollution-related inflammation. These findings and the racial/ethnic and gender differences observed deserve further exploration

An efficient approach for surveillance of childhood diabetes by type derived from electronic health record data: the SEARCH for Diabetes in Youth Study

Objective To develop an efficient surveillance approach for childhood diabetes by type across 2 large US health care systems, using phenotyping algorithms derived from electronic health record (EHR) data