| 1. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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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.
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| 2. |
- Sharma, Ashok, et al.
(författare)
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Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3, s. 0152476-0152476
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prospective cohort study.METHODS: A total of 424,788 newborns from the US and European general populations and first-degree relatives with type 1 diabetes were screened for specific HLA genotypes. Of these, 21,589 carried 1 of the 9 HLA genotypes associated with increased risk for type 1 diabetes and celiac disease; we followed 8676 of the children in a 15 y prospective follow-up study. Genotype analyses were performed on 6010 children using the Illumina ImmunoChip. Levels of tTGA were measured in serum samples using radio-ligand binding assays; diagnoses of celiac disease were made based on persistent detection of tTGA and biopsy analysis. Data were analyzed using Cox proportional hazards analyses.RESULTS: We found 54 single-nucleotide polymorphisms (SNPs) in 5 genes associated with celiac disease (TAGAP, IL18R1, RGS21, PLEK, and CCR9) in time to celiac disease analyses (10-4>P>5.8x10-6). The hazard ratios (HR) for the SNPs with the smallest P values in each region were 1.59, 1.45, 2.23, 2.64, and 1.40, respectively. Outside of regions previously associated with celiac disease, we identified 10 SNPs in 8 regions that could also be associated with the disease (P<10-4). A SNP near PKIA (rs117128341, P = 6.5x10-8, HR = 2.8) and a SNP near PFKFB3 (rs117139146, P<2.8x10-7, HR = 4.9) reached the genome-wide association threshold in subjects from Sweden. Analyses of time to detection of tTGA identified 29 SNPs in 2 regions previously associated with celiac disease (CTLA4, P = 1.3x10-6, HR = 0.76 and LPP, P = 2.8x10-5, HR = .80) and 6 SNPs in 5 regions not previously associated with celiac disease (P<10-4); non-HLA genes are therefore involved in development of tTGA.CONCLUSIONS: In conclusion, using a genetic analysis of a large international cohort of children, we associated celiac disease development with 5 non-HLA regions previously associated with the disease and 8 regions not previously associated with celiac disease. We identified 5 regions associated with development of tTGA. Two loci associated with celiac disease progression reached a genome-wide association threshold in subjects from Sweden.
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| 3. |
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| 4. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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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.
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| 5. |
- Larsson, Helena Elding, et al.
(författare)
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Growth and risk for islet autoimmunity and progression to type 1 diabetes in early childhood : The environmental determinants of diabetes in the young study
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:7, s. 1988-1995
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Tidskriftsartikel (refereegranskat)abstract
- Increased growth in early childhood has been suggested to increase the risk of type 1 diabetes. This study explored the relationship between weight or height and development of persistent islet autoimmunity and progression to type 1 diabetes during the first 4 years of life in 7,468 children at genetic risk for type 1 diabetes followed in Finland, Germany, Sweden, and the U.S. Growth data collected every third month were used to estimate individual growth curves by mixed models. Cox proportional hazards models were used to evaluate body size and risk of islet autoimmunity and type 1 diabetes. In the overall cohort, development of islet autoimmunity (n = 575) was related to weight z scores at 12 months (hazard ratio [HR] 1.16 per 1.14 kg in males or per 1.02 kg in females, 95% CI 1.06-1.27, P <0.001, false discovery rate [FDR] = 0.008) but not at 24 or 36 months. A similar relationship was seen between weight z scores and development of multiple islet autoantibodies (1 year: HR 1.21, 95% CI 1.08-1.35, P = 0.001, FDR = 0.008; 2 years: HR 1.18, 95% CI 1.06-1.32, P = 0.004, FDR = 0.02). No association was found between weight or height and type 1 diabetes (n = 169). In conclusion, greater weight in the first years of life was associated with an increased risk of islet autoimmunity.
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| 6. |
- Silvis, Katherine, et al.
(författare)
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Maternal dietary supplement use and development of islet autoimmunity in the offspring : TEDDY study
- 2019
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 20:1, s. 86-92
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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.
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| 7. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 8. |
- Uusitalo, Ulla, et al.
(författare)
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Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study.
- 2015
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Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6211 .- 2168-6203. ; 170:1, s. 20-28
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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.
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