| 1. |
- Andrén Aronsson, Carin, et al.
(författare)
-
Age at Gluten Introduction and Risk of Celiac Disease.
- 2015
-
Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:2, s. 239-245
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 2. |
- Andrén Aronsson, Carin, et al.
(författare)
-
Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk
- 2019
-
Ingår i: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 322:6, s. 514-523
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 3. |
- Haghighi, Mona, et al.
(författare)
-
A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
|
|
| 4. |
- Hummel, Sandra, et al.
(författare)
-
First infant formula type and risk of islet autoimmunity in the environmental determinants of diabetes in the young (TEDDY) study
- 2017
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:3, s. 398-404
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow'smilk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort. RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively monitors 8,676 children at increased genetic risk for T1D. Autoantibodies to insulin, GAD65, and IA2 were measured regularly to define islet autoimmunity. Information on formula feeding was collected by questionnaires at 3 months of age. RESULTS In survival analyses, after adjustment for family history with T1D, HLA genotype, sex, country, delivery mode, breast-feeding 3 months, and seasonality of birth, we observed no significant association with islet autoimmunity in infants who received extensively hydrolyzed compared with nonhydrolyzed cow'smilk-based formula as the first formula during the first 3 months (adjusted hazard ratio 1.38 [95% CI 0.95; 2.01]), and a significantly increased risk for extensively hydrolyzed formula introduced during the first 7 days (adjusted hazard ratio 1.57 [1.04; 2.38]). Using a partially hydrolyzed or other formula as the first formula, or no formula, was not associated with islet autoimmunity risk. CONCLUSIONS These results add to the existing evidence that islet autoimmunity risk is not reduced, and may be increased, by using hydrolyzed compared with nonhydrolyzed cow's milk-based infant formula as the first formula in infants at increased genetic risk for T1D .
|
|
| 5. |
- Li, Qian, et al.
(författare)
-
Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes : the TEDDY Study
- 2021
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:1, s. 282-292
-
Tidskriftsartikel (refereegranskat)abstract
- Children'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.
|
|
| 6. |
- Lundgren, Markus, et al.
(författare)
-
Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
|
|
| 7. |
- Norris, Jill M., et al.
(författare)
-
Plasma 25-Hydroxyvitamin D concentration and risk of islet autoimmunity
- 2018
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:1, s. 146-154
-
Tidskriftsartikel (refereegranskat)abstract
- 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 casecontrol study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentrationwas measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA 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 VDR rs7975232 (interaction P = 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 VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.
|
|
| 8. |
- Silvis, Katherine, et al.
(författare)
-
Maternal dietary supplement use and development of islet autoimmunity in the offspring : TEDDY study
- 2019
-
Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 20:1, s. 86-92
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the association between maternal use of vitamin D and omega-3 fatty acids (n-3 FAs) supplements during pregnancy and risk of islet autoimmunity (IA) in the offspring. Methods: The Environmental Determinants of Diabetes in the Young (TEDDY) Study is prospectively following 8676 children with increased genetic risk for type 1 diabetes in Finland, Germany, Sweden, and the United States. Blood samples were collected every 3 months between 3 and 48 months of age then every 6 months thereafter to determine persistent IA. Duration, frequency, and supplement dose during pregnancy were recalled by mothers at 3 to 4 months postpartum. Cumulative intakes of supplemental vitamin D and n-3 FAs were analyzed as continuous or binary variables. We applied time-to-event analysis to study the association between maternal supplement use and IA, adjusting for country, human leukocyte antigen-DR-DQ genotype, family history of type 1 diabetes and sex. Secondary outcomes included insulin autoantibodies (IAA) or glutamic acid decarboxylase (GADA) as the first appearing autoantibody. Results: As of February 2018, there were 747 (9.0%) children with IA. Vitamin D supplement intake during pregnancy (any vs none) was not associated with risk for IA (hazard ratio [HR] 1.11; 95% confidence interval [CI] 0.94, 1.31); neither was cumulative vitamin D supplement intake. Supplemental n-3 FA intake was similarly not associated with IA risk (HR: 1.19, 95% CI 0.98, 1.45). Similar lack of association was observed for either IAA or GADA as the first appearing autoantibody. Conclusions: The TEDDY cohort showed no evidence of benefit regarding IA risk for vitamin D or n-3 FA supplementation during pregnancy.
|
|
| 9. |
- Thorsen, Steffen U, et al.
(författare)
-
Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload : Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
- 2023
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:5, s. 1014-1018
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.
|
|
| 10. |
- Uusitalo, Ulla, et al.
(författare)
-
Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study.
- 2015
-
Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6211 .- 2168-6203. ; 170:1, s. 20-28
-
Tidskriftsartikel (refereegranskat)abstract
- Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity.
|
|
