Participant Experiences in the Environmental Determinants of Diabetes in the Young Study: Common Reasons for Withdrawing.

Background: To characterize participant reasons for withdrawing from a diabetes focused longitudinal clinical observational trial (TEDDY) during the first three study years.

Methods: 8677 children were recruited into the TEDDY study. At participant withdrawal staff recorded any reason parents provided for withdrawal.

Reduced β-cell function in early preclinical type 1 diabetes.

Objective: We aimed to characterize insulin responses to i.v. glucose during the preclinical period of type 1 diabetes starting from the emergence of islet autoimmunity.

Predicting Later Study Withdrawal in Participants Active in a Longitudinal Birth Cohort Study for 1 Year: The TEDDY Study.

Objective: To identify predictors of later study withdrawal among participants active in The Environmental Determinants of Diabetes in the Young (TEDDY) for 1 year. 

Methods: Multiple logistic regression was used to discriminate 3,042 children active in TEDDY for the first 3 years from 432 children who withdrew in Years 2 or 3. Predictor variables were tested in blocks-demographic, maternal lifestyle behaviors, stress and child illness, maternal reactions to child's increased diabetes risk, in-study behaviors-and a final best model developed.

Serum proteomes distinguish children developing type 1 diabetes in a cohort with HLA-conferred susceptibility.

We determined longitudinal serum proteomics profiles from children with HLA-conferred diabetes susceptibility to identify changes that could be detected before seroconversion and positivity for disease-associated autoantibodies. Comparisons were made between children who seroconverted and progressed to type 1 diabetes (progressors) and those who remained autoantibody negative, matched by age, sex, sample periodicity, and risk group. The samples represented the prediabetic period and ranged from the age of 3 months to 12 years.

Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes.

The incidence of the autoimmune disease, type 1 diabetes (T1D), has increased dramatically over the last half century in many developed countries and is particularly high in Finland and other Nordic countries. Along with genetic predisposition, environmental factors are thought to play a critical role in this increase. As with other autoimmune diseases, the gut microbiome is thought to play a potential role in controlling progression to T1D in children with high genetic risk, but we know little about how the gut microbiome develops in children with high genetic risk for T1D.

Maternal anxiety about a child's diabetes risk in the TEDDY study: the potential role of life stress, postpartum depression, and risk perception.

Objective: To understand the association between life stress, postpartum depression (PD), maternal perception of her child's risk for type 1 diabetes (T1D) and a mother's anxiety about her child's T1D risk in mothers of genetically at risk children in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Methods: A short form of the state component (SAI) of the State-Trait Anxiety Inventory, negative life events (LE), the Edinburgh Postnatal Depression Scale (EPDS), and one question about the child's risk of developing T1D risk perceptions (RP) were given to mothers at the 6-month TEDDY clinic visit. The relationship between the four measures was modeled using multiple regressions.

Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.

The insult leading to autoantibody development in children who will progress to develop type 1 diabetes (T1D) has remained elusive. To investigate the genes and molecular pathways in the pathogenesis of this disease, we performed genome-wide transcriptomics analysis on a unique series of prospective whole-blood RNA samples from at-risk children collected in the Finnish Type 1 Diabetes Prediction and Prevention study. We studied 28 autoantibody-positive children, out of which 22 progressed to clinical disease.

Factors associated with maternal-reported actions to prevent type 1 diabetes in the first year of the TEDDY study.

Objective: Mothers of children at risk for type 1 diabetes report engaging in preventive behaviors. The purpose of this study is to further document these actions in an international, longitudinal sample and examine variables that predict whether mothers engage in these behaviors.

Research Design And Methods: This study examined an international sample (from Finland, Germany, Sweden, and the U.

Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes.

The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study.

Virus infections among young children--the first year of the INDIS study.

The frequencies of early childhood infections were studied in healthy children with increased genetic risk for type 1 diabetes participating in the ongoing prospective high intensive infection follow-up Study, INDIS, started in 2009 in Turku, Finland. Here the results obtained from 160 stool to 160 nasal swab specimens collected in parallel at times of infectious symptoms in 2009-2010 from 45 children at the age of 24 months or younger are reported. The specimens were analyzed for enteric (human enterovirus, norovirus, rotavirus, sapovirus, astrovirus) and respiratory RNA viruses (human enterovirus and rhinovirus) common in early childhood, respectively, using highly validated virus-specific real-time PCR methods.

Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children.

Importance: Type 1 diabetes usually has a preclinical phase identified by circulating islet autoantibodies, but the rate of progression to diabetes after seroconversion to islet autoantibodies is uncertain.

Objective: To determine the rate of progression to diabetes after islet autoantibody seroconversion.

Design, Setting, And Participants: Data were pooled from prospective cohort studies performed in Colorado (recruitment, 1993-2006), Finland (recruitment, 1994-2009), and Germany (recruitment, 1989-2006) examining children genetically at risk for type 1 diabetes for the development of insulin autoantibodies, glutamic acid decarboxylase 65 (GAD65) autoantibodies, insulinoma antigen 2 (IA2) autoantibodies, and diabetes.

Differences in recruitment and early retention among ethnic minority participants in a large pediatric cohort: the TEDDY Study.

Objective: The TEDDY Study is an international, multi-center prospective study designed to identify the environmental triggers of type 1 diabetes (T1D) in genetically at-risk children. This report investigates ethnic minority (EM) differences in patterns of enrollment and retention in the US centers.

Methods: As of June 2009, 267,739 newborns had been screened at birth for high risk T1D genotypes.

Reasons for Staying as a Participant in the Environmental Determinants of Diabetes in the Young (TEDDY) Longitudinal Study.

Objective: To assess parents' opinions about their participation in the longitudinal, multicenter study - The Environmental Determinants of Diabetes in the Young (TEDDY) consortium.

Methods: A survey was given to parents who had been in the study for ≥ 1 year. Parents rated the importance of different reasons for staying in TEDDY and how well different study components were working.

Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes.

Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e.

Impact of intranasal insulin on insulin antibody affinity and isotypes in young children with HLA-conferred susceptibility to type 1 diabetes.

Objective: Despite promising results from studies on mouse models, intranasal insulin failed to prevent or delay the development of type 1 diabetes in autoantibody-positive children with HLA-conferred disease susceptibility. To analyze whether the insulin dose was inadequate to elicit an immunomodulatory response, we compared the changes observed in insulin antibody (IA) affinity and isotypes after treatment with nasal insulin or placebo.

Research Design And Methods: Ninety-five children (47 in the placebo group and 48 in the insulin group of the total of 224 children randomized for the trial) with HLA-conferred susceptibility to type 1 diabetes derived from the intervention arm of the Finnish Type 1 Diabetes Prediction and Prevention study were included in these analyses.

Enrollment experiences in a pediatric longitudinal observational study: The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Objective: Our objective was to identify characteristics of infants and their families who were enrolled, refused to enroll, or were excluded from The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Method: 16,435 infants screened at birth and identified as at increased genetic risk for type 1 diabetes (T1DM) were placed into one of three categories: enrolled, excluded, or refused to enroll. Enrollment, exclusion and refusal rates were compared across countries and between infants from the general population (GP) and infants with a first degree T1DM relative (FDR).

The Environmental Determinants of Diabetes in the Young (TEDDY) study: predictors of early study withdrawal among participants with no family history of type 1 diabetes.

Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental triggers of autoimmunity and type 1 diabetes mellitus (T1DM) in children at increased human-leukocyte-antigen conferred genetic risk for this disease. The objective of this study was to identify predictors of early withdrawal from TEDDY among families with no immediate family history of T1DM.

Method: Logistic multiple regression was used to discriminate 2994 (83%) families currently active in the TEDDY study for ≥1 yr from 763 (17%) families who withdrew in the first year.

Toward defining the autoimmune microbiome for type 1 diabetes.

Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed.

Early suppression of immune response pathways characterizes children with prediabetes in genome-wide gene expression profiling.

Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing pancreatic beta cells in the islets of Langerhans. Although defects in various T cell subsets have been linked to the disease pathogenesis, mechanisms initiating or enhancing the autoimmunity in prediabetes remain poorly understood. To unravel genes and molecular pathways affected by the diabetes-associated autoimmunity, we investigated transcriptomic profiles of prospective whole-blood samples from children who have developed T1D-associated autoantibodies and eventually clinical T1D.

Predictive characteristics of diabetes-associated autoantibodies among children with HLA-conferred disease susceptibility in the general population.

Objective: As data on the predictive characteristics of diabetes-associated autoantibodies for type 1 diabetes in the general population are scarce, we assessed the predictive performance of islet cell autoantibodies (ICAs) in combination with autoantibodies against insulin (IAAs), autoantibodies against GAD, and/or islet antigen 2 for type 1 diabetes in children with HLA-defined disease predisposition recruited from the general population.

Research Design And Methods: We observed 7,410 children from birth (median 9.2 years) for beta-cell autoimmunity and diabetes.

From genetic risk awareness to overt type 1 diabetes: parental stress in a placebo-controlled prevention trial.

Objective: To evaluate the psychological burden of parents facing increasing risk of type 1 diabetes in their children.

Research Design And Methods: In the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Study, newborn infants with HLA-DQB1-conferred diabetes risk were enrolled in sequential analyses of diabetes-associated autoantibodies. Those persistently positive for at least two autoantibodies were recruited to a randomized double-blinded intervention trial.

Role of insulin autoantibody affinity as a predictive marker for type 1 diabetes in young children with HLA-conferred disease susceptibility.

Background: Insulin autoantibodies (IAA) are early markers of prediabetic autoimmunity. As transient and fluctuating IAA positivity are common among young children, distinguishing non-progressive IAA from destruction-related IAA is essential when preventive measures are considered. We tested whether children progressing rapidly to type 1 diabetes (progressors) are characterized by a higher prediabetic IAA affinity than IAA-positive children remaining unaffected or progressing more slowly to diabetes (non-progressors), and whether IAA affinity increases towards diagnosis.

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes.

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward beta cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative.

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial.

Background: In mouse models of diabetes, prophylactic administration of insulin reduced incidence of the disease. We investigated whether administration of nasal insulin decreased the incidence of type 1 diabetes, in children with HLA genotypes and autoantibodies increasing the risk of the disease.

Methods: At three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed cord blood samples of 116 720 consecutively born infants, and 3430 of their siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes.