620 research outputs found
Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children [Elektronisk resurs]
No full textAims/hypothesis: During the A/H1N1 2009 (A/California/04/2009) pandemic, mass vaccination with a squalene-containing vaccine, Pandemrix®, was performed in Sweden and Finland. The vaccination was found to cause narcolepsy in children and young adults with the HLA-DQ 6.2 haplotype. The aim of this study was to investigate if exposure to Pandemrix® similarly increased the risk of islet autoimmunity or type 1 diabetes. Methods: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, children are followed prospectively for the development of islet autoimmunity and type 1 diabetes. In October 2009, when the mass vaccination began, 3401 children at risk for islet autoimmunity and type 1 diabetes were followed in Sweden and Finland. Vaccinations were recorded and autoantibodies against insulin, GAD65 and insulinoma-associated protein 2 were ascertained quarterly before the age of 4 years and semi-annually thereafter. Results: By 5 August 2010, 2413 of the 3401 (71%) children observed as at risk for an islet autoantibody or type 1 diabetes on 1 October 2009 had been vaccinated with Pandemrix®. By 31 July 2016, 232 children had at least one islet autoantibody before 10 years of age, 148 had multiple islet autoantibodies and 96 had developed type 1 diabetes. The risk of islet autoimmunity was not increased among vaccinated children. The HR (95% CI) for the appearance of at least one islet autoantibody was 0.75 (0.55, 1.03), at least two autoantibodies was 0.85 (0.57, 1.26) and type 1 diabetes was 0.67 (0.42, 1.07). In Finland, but not in Sweden, vaccinated children had a lower risk of islet autoimmunity (0.47 [0.29, 0.75]), multiple autoantibodies (0.50 [0.28, 0.90]) and type 1 diabetes (0.38 [0.20, 0.72]) compared with those who did not receive Pandemrix®. The analyses were adjusted for confounding factors. Conclusions/interpretation: Children with an increased genetic risk for type 1 diabetes who received the Pandemrix® vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes
Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes the TEDDY Study
No full textChildren's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression
Parental estimation of their child's increased type 1 diabetes risk during the first 2 years of participation in an international observational study : Results from the TEDDY study
No full textThis study assessed mothers' and fathers' perception of their child's risk of getting type I diabetes (TID) during the first 2 years of their participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study. TEDDY parents were informed of their child's increased genetic risk for Tl D at study inception. Parent perception of the child's risk was assessed at 3, 6, 15, and 27 months of age. In families with no history of TID, underestimation of the child's TID risk was common in mothers (>38%) and more so in fathers (>50%). The analyses indicated that parental education, country of residence, family history of TID, household crowding, ethnic minority status, and beliefs that the child's TID risk can be reduced were factors associated with parental risk perception accuracy. Even when given extensive information about their child's TID risk, parents often fail to accurately grasp the information provided. This is particularly true for fathers, families from low socioeconomic backgrounds, and those with no family history of Tl D. It is important to develop improved tools for risk communication tailored to individual family needs
Is staff consistency important to parents’ satisfaction in a longitudinal study of children at risk for type 1 diabetes : the TEDDY study
No full textBackground: Participants’ study satisfaction is important for both compliance with study protocols and retention, but research on parent study satisfaction is rare. This study sought to identify factors associated with parent study satisfaction in The Environmental Determinants of Diabetes in the Young (TEDDY) study, a longitudinal, multinational (US, Finland, Germany, Sweden) study of children at risk for type 1 diabetes. The role of staff consistency to parent study satisfaction was a particular focus. Methods: Parent study satisfaction was measured by questionnaire at child-age 15 months (5579 mothers, 4942 fathers) and child-age four years (4010 mothers, 3411 fathers). Multiple linear regression analyses were used to identify sociodemographic factors, parental characteristics, and study variables associated with parent study satisfaction at both time points. Results: Parent study satisfaction was highest in Sweden and the US, compared to Finland. Parents who had an accurate perception of their child’s type 1 diabetes risk and those who believed they can do something to prevent type 1 diabetes were more satisfied. More educated parents and those with higher depression scores had lower study satisfaction scores. After adjusting for these factors, greater study staff change frequency was associated with lower study satisfaction in European parents (mothers at child-age 15 months: − 0.30,95% Cl − 0.36, − 0.24, p < 0.001; mothers at child-age four years: -0.41, 95% Cl − 0.53, − 0.29, p < 0.001; fathers at child-age 15 months: -0.28, 95% Cl − 0.34, − 0.21, p < 0.001; fathers at child-age four years: -0.35, 95% Cl − 0.48, − 0.21, p < 0.001). Staff consistency was not associated with parent study satisfaction in the US. However, the number of staff changes was markedly higher in the US compared to Europe. Conclusions: Sociodemographic factors, parental characteristics, and study-related variables were all related to parent study satisfaction. Those that are potentially modifiable are of particular interest as possible targets of future efforts to improve parent study satisfaction. Three such factors were identified: parent accuracy about the child’s type 1 diabetes risk, parent beliefs that something can be done to reduce the child’s risk, and study staff consistency. However, staff consistency was important only for European parents. Trial registration: NCT00279318.Peer reviewe
Participant Experiences in the Environmental Determinants of Diabetes in the Young Study : Common Reasons for Withdrawing
No full textBackground. 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. Reasons were categorized into (1) family characteristics and (2) protocol reasons. Families who informed staff of their withdrawal were classified as active withdrawals (AW); families without a final contact were considered passive withdrawals (PW). Results. Withdrawal was highest during the first study year (n = 1220). Most families were AW(n = 1549; 73.4%). PW was more common in the United States (n = 1001; 37.8%) and among young mothers (p = 0.001). The most frequent protocol characteristic was blood draw (55%) and the most common family reason was not having enough time (66%). The blood draw was more common among female participants; being too busy was more common among males. Both reasons were associated with study satisfaction. Conclusions. Results suggest that, for families of children genetically at risk for diabetes, procedures that can be painful/frightening should be used with caution. Study procedures must also be considered for the demands placed on participants. Study satisfaction should be regularly assessed as an indicator of risk for withdrawal.Peer reviewe
Diabetes Care
No full textOBJECTIVEYoung children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries.RESEARCH DESIGN AND METHODSSymptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register).RESULTSA total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children <2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P < 0.0001; Swediabkids, P = 0.02; SEARCH, P < 0.0001; Finnish Register, P < 0.0001). The prevalence of DKA in TEDDY children diagnosed at <5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P < 0.0001) and the German DPV Register (32.2%) (P < 0.0001) but not compared with Swediabkids or the Finnish Register.CONCLUSIONSParticipation in the TEDDY study is associated with reduced risk of DKA at diagnosis of type 1 diabetes in young children.20111U18DP002709/DP/NCCDPHP CDC HHS/United StatesDK-63790/DK/NIDDK NIH HHS/United StatesDK-63821/DK/NIDDK NIH HHS/United StatesDK-63829/DK/NIDDK NIH HHS/United StatesDK-63836/DK/NIDDK NIH HHS/United StatesDK-63861/DK/NIDDK NIH HHS/United StatesDK-63863/DK/NIDDK NIH HHS/United StatesDK-63865/DK/NIDDK NIH HHS/United StatesU01 DK063865/DK/NIDDK NIH HHS/United StatesU01 DP000244/DP/NCCDPHP CDC HHS/United StatesU01 DP000246/DP/NCCDPHP CDC HHS/United StatesU01 DP000247/DP/NCCDPHP CDC HHS/United StatesU01 DP000248/DP/NCCDPHP CDC HHS/United StatesU01 DP000250/DP/NCCDPHP CDC HHS/United StatesU01 DP000254/DP/NCCDPHP CDC HHS/United StatesU01DP000245/DP/NCCDPHP CDC HHS/United StatesU18DP000247-06A1/DP/NCCDPHP CDC HHS/United StatesU18DP002708-01/DP/NCCDPHP CDC HHS/United StatesU18DP002710-01/DP/NCCDPHP CDC HHS/United StatesU18DP002714/DP/NCCDPHP CDC HHS/United StatesU58CCU919256/PHS HHS/United StatesUC4 DK063821/DK/NIDDK NIH HHS/United StatesUC4 DK063865/DK/NIDDK NIH HHS/United StatesUL1 RR025014/RR/NCRR NIH HHS/United States21972409PMC31982961161
Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study
No full textObjective: The Environmental Determinants
of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific
differences associated with type 1 diabetes. As age is a primary driver of
heterogeneity in type 1 diabetes, we sought to characterize by age, metabolic
derangements prior to diagnosis and clinical features associated with diabetic
ketoacidosis (DKA).
Research Design and
Methods:
The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset
(0-4, 5-9, and 10-14 years; n=142, 151 and 86, respectively) with comparisons
of autoantibody profiles, HLA, family history of diabetes, presence of DKA,
symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis
of those with OGTT data was compared to TEDDY children who did not progress to
diabetes.
Results: Increasing fasting
glucose (HR=1.09 (95% CI 1.04-1.14), p=0.0003), stimulated glucose (HR=1.50 (1.42-1.59),
p<0.0001), fasting insulin (HR=0.89 (0.83-0.95), p=0.0009), and glucose-to-insulin
ratio (HR=1.29 (1.16-1.43), p<0.0001) were associated with risk of
progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms
at diagnosis. Of 23/379 (6.1%) children with DKA at onset, only 1/23 (4.3%) had
a first-degree relative (FDR) with type 1 diabetes compared to 102/356 (28.7%) FDR children without DKA (p=0.008).
Children in DKA were more likely to be non-adherent to study protocol (p=0.047),
with longer duration between their last TEDDY evaluation and diagnosis (median
10.2 vs 2.0 months without DKA, p<0.001).
Conclusions: DKA at onset in TEDDY
is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring
continues to provide a primary benefit of reduced DKA but requires regular
follow-up. Clinical and laboratory features vary by age at onset adding to the
heterogeneity of type 1 diabetes.</p
Predicting later study withdrawal in participants active in a longitudinal birth cohort study for 1 year: The TEDDY study.
No full textOBJECTIVE : 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.  RESULTS : Few demographic factors predicted study withdrawal. Maternal lifestyle behaviors, accuracy of the mother's risk perception, and in-study behaviors were more important. Frequent child illnesses were associated with greater study retention.  CONCLUSIONS : Demographic measures are insufficient predictors of later study withdrawal among those active in a study for at least 1 year; behavioral/psychological factors offer improved prediction and guidance for the development of retention strategies
Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes: the TEDDY study
No full textAims/hypothesis: We studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes.Methods: We used a risk set sampled nested case–control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification.Results: Childhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]).Conclusions/interpretation: Higher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings.Data availability: The datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://www.niddkrepository.org/studies/teddy.</p
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