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Background 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 p p p 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.

BACKGROUND: High gluten intake is associated with increased risk of celiac disease (CD) in children at genetic risk. OBJECTIVES: We aimed to investigate if different dietary gluten sources up to age 2 y confer different risks of celiac disease autoimmunity (CDA) and CD in children at genetic risk. METHODS: Three-day food records were collected at ages 6, 9, 12, 18, and 24 mo from 2088 Swedish genetically at-risk children participating in a 15-y follow-up cohort study on type 1 diabetes and CD. Screening for CD was performed with tissue transglutaminase autoantibodies (tTGA). The primary outcome was CDA, defined as persistent tTGA positivity. The secondary outcome was CD, defined as having a biopsy specimen showing Marsh score≥2 or an averaged tTGA level≥100 Units. Cox regression adjusted for total gluten intake estimated HRs with 95% CIs for daily intake of gluten sources. RESULTS: During follow-up, 487 (23.3%) children developed CDA and 242 (11.6%) developed CD. Daily intake of ≤158g porridge at age 9 mo was associated with increased risk of CDA (HR: 1.53; 95% CI: 1.05, 2.23; P=0.026) compared with no intake. A high daily bread intake (>18.3g) at age 12 mo was associated with increased risk of both CDA (HR: 1.47; 95% CI: 1.05, 2.05; P=0.023) and CD (HR: 1.79; 95% CI: 1.10, 2.91; P=0.019) compared with no intake. At age 18 mo, milk cereal drink was associated with an increased risk of CD (HR: 1.16; 95% CI: 1.00, 1.33; P=0.047) per 200-g/d increased intake. No association was found for other gluten sources up to age 24 mo and risk of CDA or CD. CONCLUSIONS: High daily intakes of bread at age 12 mo and of milk cereal drink during the second year of life are associated with increased risk of both CDA and CD in genetically at-risk children.

Aims/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.

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring's risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997-2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring. publishedVersion

BACKGROUND: High dietary intake of nitrate and nitrite might increase the risk of type 1 diabetes. To our knowledge, no earlier prospective study has explored whether maternal dietary intake of nitrate and nitrite during pregnancy is associated with the risk of type 1 diabetes in the offspring. OBJECTIVE: Our aim was to study association between maternal intake of nitrate and nitrite during pregnancy and the risk of islet autoimmunity and type 1 diabetes in the offspring. DESIGN: Children born between 1997 and 2004 at Oulu and Tampere University Hospitals in Finland and carrying increased human leukocyte antigen (HLA)-conferred risk for type 1 diabetes were followed in the Type 1 Diabetes Prediction and Prevention (DIPP) study from 3 mo of age. Islet autoantibodies were screened at 3- to 12-mo intervals from serum samples. Of 4879 children, 312 developed islet autoimmunity and 178 developed type 1 diabetes during a 15-y follow-up. Maternal intake of nitrate and nitrite during the eighth month of pregnancy was assessed after birth using a validated self-administered FFQ. Cox proportional hazards regression was used for the statistical analyses. RESULTS: Maternal intake of nitrate and nitrite during pregnancy was not associated with the child's risk of islet autoimmunity [nitrate: HR 0.99 (95% CI: 0.88, 1.11); nitrite: HR 1.03 (95% CI: 0.92, 1.15)] or type 1 diabetes [nitrate: HR 1.02 (95% CI: 0.88, 1.17); nitrite: HR 0.97 (95% CI: 0.83, 1.12)] when adjusted for energy (residual method), sex, HLA risk group, and family history of diabetes. Further adjustment for dietary antioxidants (vitamin C, vitamin E, and selenium) did not change the results. CONCLUSION: Maternal dietary intake of nitrate or nitrite during pregnancy is not associated with the risk of islet autoimmunity or type 1 diabetes in the offspring genetically at risk for type 1 diabetes. acceptedVersion

Islet autoantibodies (IAs) precede the clinical onset of type 1 diabetes (T1D); however, the knowledge is limited about whether the prodrome affects complete blood counts (CBCs) in 4- to 12-year-old children with increased genetic risk for T1D. This study tested whether CBCs were altered in 4- to 12-year-old children without (n = 376) or with one or several IAs against insulin, GAD65, or IA-2 (n = 72). CBC was analyzed during longitudinal follow-up in 448 Swedish children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A linear mixed-effects model was used to assess potential association between IA and CBC measurements over time. The white blood cell and neutrophil counts were reduced in children with IAs, primarily in boys. In contrast, girls had lower levels of hemoglobin and hematocrit. Positivity for multiple IAs showed the lowest counts in white blood cells and neutrophils in boys and red blood cells, hemoglobin, and hematocrit in girls. These associations were primarily observed in children with the HLA-DR3-DQ2/DR4-DQ8 genotype. We conclude that the reduction in neutrophils and red blood cells in children with multiple IAs and HLA-DR3-DQ2/DR4-DQ8 genotype may signal a sex-dependent islet autoimmunity detected in longitudinal CBCs.

PURPOSE OF REVIEW: The environmental triggers of islet autoimmunity leading to type 1 diabetes (T1D) need to be elucidated to inform primary prevention. The Environmental Determinants of Diabetes in the Young (TEDDY) Study follows from birth 8676 children with T1D risk HLA-DR-DQ genotypes in the USA, Finland, Germany, and Sweden. Most study participants (89%) have no first-degree relative with T1D. The primary outcomes include the appearance of one or more persistent islet autoantibodies (islet autoimmunity, IA) and clinical T1D. RECENT FINDINGS: As of February 28,2018, 769 children had developed IA and 310 have progressed to T1D. Secondary outcomes include celiac disease and autoimmune thyroid disease. While the follow-up continues, TEDDY has already evaluated a number of candidate environmental triggers, including infections, probiotics, micronutrient, and microbiome. SUMMARY: TEDDY results suggest that there are multiple pathways leading to the destruction of pancreatic beta-cells. Ongoing measurements of further specific exposures, gene variants, and gene-environment interactions and detailed “omics” studies will provide novel information on the pathogenesis of T1D.