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; for the TEDDY Study Group IMPORTANCE High gluten intake during childhood may confer risk of celiac disease. OBJECTIVES To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. DESIGN, SETTING, AND PARTICIPANTS The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. EXPOSURES Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. MAIN OUTCOMES AND MEASURES The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. RESULTS Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). CONCLUSIONS AND RELEVANCE Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

OBJECTIVES: The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. METHODS: TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. RESULTS: Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7–8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47–2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34–2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. CONCLUSIONS: In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.

Aims/hypothesis. Morphometric and passive biomechanical properties were studied in the duodenum, jejunum and ileum in 10 non-diabetic and 40 streptozotocin-induced diabetic rats. Methods. The diabetic rats were divided into groups living 4 days, 1, 2, and 4 weeks after diabetes was induced (n=10 for each groups). The mechanical test was done as a ramp distension experiment. The intestinal diameter and length were obtained from digitised images of the intestinal segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state geometry. Results. The blood glucose concentration increased four-to fivefold in the diabetic rats. Streptozotocin-induced diabetes generated pronounced increase in the weight per centimetre length, wall thickness and wall cross-sectional area in all intestinal segments during diabetes (p<0.05). Histological analysis showed that the thickness of the intestinal layers was increased in all segments during diabetes (p<0.05). In the duodenum the opening angle did not change in the first 2 weeks and decreased after 4 weeks (p<0.05). In the jejunum and ileum the opening angle increased after 1 week in the diabetic group. The residual strain showed the same pattern as the opening angle. Furthermore, it was found that the circumferential and longitudinal stiffness of the intestinal wall increased with the duration of diabetes (p<0.05 and p<0.01). Conclusion/interpretation. Morphological and biomechanical remodelling of the small intestine occurred during the development of diabetes. [Diabetologia (2003[Diabetologia ( ) 46:1688[Diabetologia ( -1697

We examined the association between plasma 25-hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in , and were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by rs7975232 (interaction = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.

Objectives The aim of the present study was to examine the prevalence and associated factors of dietary supplement use, particularly supplements containing vitamin D and fatty acids, in pregnant women enrolled in a multi-national study. Design The Environmental Determinants of Diabetes in the Young (TEDDY) study is a prospective longitudinal cohort study. Maternal dietary supplement use was self-reported through questionnaires at month 3 to 4 postpartum. Setting Six clinical research centres; three in the USA (Colorado, Georgia/Florida and Washington) and three in Europe (Sweden, Finland and Germany). Subjects Mothers (n 7326) to infants screened for high-risk HLA-DQ genotypes of type 1 diabetes. Results Ninety-two per cent of the 7326 women used one or more types of supplement during pregnancy. Vitamin D supplements were taken by 65 % of the women, with the highest proportion of users in the USA (80·5 %). Overall, 16 % of the women reported taking fatty acid supplements and a growing trend was seen in all countries between 2004 and 2010 (P < 0·0001). The use was more common in Germany (32 %) and the USA (24 %) compared with Finland (8·5 %) and Sweden (7·0 %). Being pregnant with the first child was a strong predictor for any supplement use in all countries. Low maternal age (<25 years), higher education, BMI ≥ 25·0 kg/m2 and smoking during pregnancy were factors associated with supplement use in some but not all countries. Conclusions The majority of the women used dietary supplements during pregnancy. The use was associated with sociodemographic and behavioural factors, such as parity, maternal age, education, BMI and maternal smoking.

Background Although breastfeeding is touted as providing many health benefits to infants, some aspects of this relationship remain poorly understood. Methods The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective longitudinal study that follows children from birth through childhood, and collects data on illness events, breastfeeding duration, and time to introduction of formula or foods at 3 month intervals up until 4 years of age and at 6 months intervals thereafter. Exclusive and non-exclusive breastfeeding is examined in relation to the 3-month odds of a respiratory or gastrointestinal infection for 6861 children between the ages of 3–18 months, and 5666 children up to the age of 4 years. Analysis was performed using logistic regression models with generalized estimating equation methodology. All models were adjusted for potential confounding variables. Results At 3–6 months of age, breastfeeding was found to be inversely associated with the odds of respiratory infections with fever (OR = 0.82, 95% CI = 0.70–0.95), otitis media (OR = 0.76, 95% CI = 0.62–0.94), and infective gastroenteritis (OR = 0.55, 95% CI = 0.46–0.70), although the inverse association with respiratory illnesses was observed only for girls during the winter months. Between 6 and 18 months of age, breastfeeding within any 3 month period continued to be inversely associated with the odds of ear infection and infective gastroenteritis, and additionally with the odds of conjunctivitis, and laryngitis and tracheitis, over the same 3 month period within this age range. However, breastfeeding in this group was associated with increased reports of common cold. Duration of exclusive breastfeeding was inversely associated with the odds of otitis media up to 48 months of age (OR = 0.97, 95% CI = 0.95–0.99) after breastfeeding had stopped. Conclusions This study demonstrates that breastfeeding can be protective against multiple respiratory and gastrointestinal acute illnesses in some children up to at least 6 months of age, with duration of exclusive breastfeeding being somewhat protective of otitis media even after breastfeeding has stopped. Trial registration ClinicalTrials.gov Identifier: NCT00279318. Date of registration: January 17, 2006 (proactively registered). First Posted: January 19, 2006.