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Purpose: Correlations between fatigue-induced changes in exercise performance and maximal rate of heart rate (HR) increase (rHRI) may be affected by exercise intensity during assessment. This study evaluated the sensitivity of rHRI for tracking performance when assessed at varying exercise intensities. Method: Performance (time to complete a 5-km treadmill time-trial [5TTT]) and rHRI were assessed in 15 male runners following 1 week of light training, 2 weeks of heavy training (HT), and a 10-day taper (T). Maximal rate of HR increase (measured in bpm·s[superscript-1]) was the first derivative maximum of a sigmoidal curve fit to HR data recorded during 5 min of running at 8 km·h[superscript -1] (rHRI[subscript 8km·h][superscript -1]), and during subsequent transition to 13 km·h[superscript -1] (rHRI[subscript 8-13km·h][superscript -1]) for a further 5 min. Results: Time to complete a 5-km treadmill time-trial was likely slower following HT (effect size ± 90% confidence interval = 0.16 ± 0.06), and almost certainly faster following T (-0.34 ± 0.08). Maximal rate of HR increase during 5 min of running at 8 km·h[superscript -1] and rHRI[subscript 8-13km·h][superscript -1] were unchanged following HT and likely increased following T (0.77 ± 0.45 and 0.66 ± 0.62, respectively). A moderate within-individual correlation was found between 5TTT and rHRI[subscript 8km·h][superscript -1] (r value ± 90% confidence interval = -0.35 ± 0.32). However, in a subgroup of athletes (n = 7) who were almost certainly slower to complete the 5TTT (4.22 ± 0.88), larger correlations were found between the 5TTT and rHRI[subscript 8km·h][superscript -1] (r = -0.84 ± 0.22) and rHRI[subscript 8-13km·h][superscript -1] (r = -0.52 ± 0.41). Steady-state HR during rHRI assessment in this group was very likely greater than in the faster subgroup (= 1.34 ± 0.86). Conclusion(s): The 5TTT performance was tracked by both rHRI[subscript 8km·h][superscript -1] and rHRI[subscript 8-13km·h][superscript -1]. Correlations between rHRI and performance were stronger in a subgroup of athletes who exhibited a slower 5TTT. Individualized workloads during rHRI assessment may be required to account for varying levels of physical conditioning.

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D. Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood. Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation. The ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically at‐risk for type 1 diabetes followed from birth who had developed islet autoantibodies ("seroconverted"), by measuring mucosa‐associated cytokines in their sera. Materials and Methods: Sera were collected 3 monthly from birth from children with a first‐degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results: Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosa‐associated cytokines IL‐21, IL‐22, IL‐25, and IL‐10, the Th17‐related cytokines IL‐17F and IL‐23, as well as IL‐33, IFN‐γ, and IL‐4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex‐ and age‐matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions: In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa‐associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity. [ABSTRACT FROM AUTHOR]

Background: We sought research experiences of caregivers and their children were enrolled in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Methods: ENDIA is a pregnancy–birth cohort investigating early-life causes of type 1 diabetes (T1D). Surveys were sent to 1090 families between June 2021 and March 2022 with a median participation of >5 years. Caregivers completed a 12-item survey. Children ≥ 3 years completed a four-item survey. Results: The surveys were completed by 550/1090 families (50.5%) and 324/847 children (38.3%). The research experience was rated as either "excellent" or "good" by 95% of caregivers, and 81% of children were either "ok", "happy" or "very happy". The caregivers were motivated by contributing to research and monitoring their children for T1D. Relationships with the research staff influenced the experience. The children most liked virtual reality headsets, toys, and "helping". Blood tests were least liked by the children and were the foremost reason that 23.4% of the caregivers considered withdrawing. The children valued gifts more than their caregivers. Only 5.9% of responses indicated dissatisfaction with some aspects of the protocol. The self-collection of samples in regional areas, or during the COVID-19 pandemic restrictions, were accepted. Conclusions: This evaluation identified modifiable protocol elements and was conducted to further improve satisfaction. What was important to the children was distinct from their caregivers. [ABSTRACT FROM AUTHOR]

Purpose: Stride-to-stride fluctuations in running-stride interval display long-range correlations that break down in the presence of fatigue accumulated during an exhaustive run. The purpose of the study was to investigate whether long-range correlations in running-stride interval were reduced by fatigue accumulated during prolonged exposure to a high training load (functional overreaching) and were associated with decrements in performance caused by functional overreaching. Methods: Ten trained male runners completed 7 d of light training (LT7), 14 d of heavy training (HT14) designed to induce a state of functional overreaching, and 10 d of light training (LT10) in a fixed order. Running-stride intervals and 5-km time-trial (5TT) performance were assessed after each training phase. The strength of long-range correlations in running-stride interval was assessed at 3 speeds (8, 10.5, and 13 km/h) using detrended fluctuation analysis. Results: Relative to performance post-LT7, time to complete the 5TT was increased after HT14 (+18 s; P < .05) and decreased after LT10 (-20 s; P = .03), but stride-interval long-range correlations remained unchanged at HT14 and LT10 (P > .50). Changes in stride-interval long-range correlations measured at a 10.5-km/h running speed were negatively associated with changes in 5TT performance (r -.46; P = .03). Conclusions: Runners who were most affected by the prolonged exposure to high training load (as evidenced by greater reductions in 5TT performance) experienced the greatest reductions in stride-interval long-range correlations. Measurement of stride-interval long-range correlations may be useful for monitoring the effect of high training loads on athlete performance. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy and type 1 diabetes are each associated with increased anxiety and depression, but the combined impact on well-being is unresolved. We compared the mental health of women with and without type 1 diabetes during pregnancy and postpartum and examined the relationship between mental health and glycemic control.Research Design and Methods: Participants were women enrolled from 2016 to 2020 in the Environmental Determinants of Islet Autoimmunity (ENDIA) study, a pregnancy to birth prospective cohort following children with a first-degree relative with type 1 diabetes. Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) were completed during the third trimester (T3) (median [interquartile range] 34 [32, 36] weeks) and postpartum (14 [13, 16] weeks) by 737 women (800 pregnancies) with (n = 518) and without (n = 282) type 1 diabetes.Results: EPDS and PSS scores did not differ between women with and without type 1 diabetes during T3 and postpartum. EPDS scores were marginally higher in T3: predicted mean (95% CI) 5.7 (5.4, 6.1) than postpartum: 5.3 (5.0, 5.6), independent of type 1 diabetes status (P = 0.01). HbA1c levels in type 1 diabetes were 6.3% [5.8, 6.9%] in T3 and did not correlate with EPDS or PSS scores. Reported use of psychotropic medications was similar in women with (n = 44 of 518 [8%]) and without type 1 diabetes (n = 17 of 282 [6%]), as was their amount of physical activity.Conclusions: Overall, mental health in late pregnancy and postpartum did not differ between women with and without type 1 diabetes, and mental health scores were not correlated with glycemic control. [ABSTRACT FROM AUTHOR]

Purpose: Heart-rate variability (HRV) as a measure of autonomic function may increase in response to training interventions leading to increases or decreases in performance, making HRV interpretation difficult in isolation. This study aimed to con-textualize changes in HRV with subjective measures of training tolerance. Methods: Supine and standing measures of vagally mediated HRV (root-mean-square difference of successive normal RR intervals [RMSSD]) and measures of training tolerance (Daily Analysis of Life Demands for Athletes questionnaire, perception of energy levels, fatigue, and muscle soreness) were recorded daily during 1 wk of light training (LT), 2 wk of heavy training (HT), and 10 d of tapering (T) in 15 male runners/ triathletes. HRV and training tolerance were analyzed as rolling 7-d averages at LT, HT, and T. Performance was assessed after LT, HT, and T with a 5-km treadmill time trial (5TTT). Results: Time to complete the 5TTT likely increased after HT (effect size [ES] ± 90% confidence interval = 0.16 ± 0.06) and then almost certainly decreased after T (ES = -0.34 ± 0.08). Training tolerance worsened after HT (ES ≥ 1.30 ± 0.41) and improved after T (ES ≥ 1.27 ± 0.49). Standing RMSSD very likely increased after HT (ES = 0.62 ± 0.26) and likely remained higher than LT at the completion of T (ES = 0.38 ± 0.21). Changes in supine RMSSD were possible or likely trivial. Conclusions: Vagally mediated HRV during standing increased in response to functional overreaching (indicating potential parasympathetic hyperactivity) and also to improvements in performance. Thus, additional measures such as training tolerance are required to interpret changes in vagally mediated HRV. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D. Results: Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage. Conclusions: Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means. 9EttwuCftMDTXMZ-D9rhTq Video abstract [ABSTRACT FROM AUTHOR]