| 1. |
- van der Valk, Ralf J P, et al.
(author)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Journal article (peer-reviewed)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 2. |
- Virtanen, S M, et al.
(author)
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Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes
- 2011
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In: ACTA PAEDIATRICA. - : Blackwell Publishing Ltd. - 0803-5253. ; 100:4, s. 557-564
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Journal article (peer-reviewed)abstract
- Aim: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study. Methods: The protocol was tested in 240 children. The diet of the participating children was assessed by self-administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months. Results: A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cows milk and casein were higher in the cows milk-based formula group than in the hydrolysed formula group during the intervention period (p andlt; 0.05), reflecting the difference in the intake of cows milk protein. Conclusion: This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.
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| 3. |
- Rasanen, M., et al.
(author)
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Intake of vitamin D by Finnish children aged 3 months to 3 years in relation to sociodemographic factors
- 2006
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In: European Journal of Clinical Nutrition. - Natl Publ Hlth Inst, Unit Nutr, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. Univ Tampere, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland. Natl Res & Dev Ctr Welf & Hlth, Helsinki, Finland. Univ Oulu, Dept Pediat, Oulu, Finland. Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland. Tampere Univ Hosp, Dept Pediat, Helsinki, Finland. Tampere Univ Hosp, Res Unit, Helsinki, Finland. : NATURE PUBLISHING GROUP. - 0954-3007 .- 1476-5640. ; 60:11, s. 1317-1322
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Journal article (peer-reviewed)abstract
- Objective: To study the total daily intake of vitamin D from food and supplements among Finnish children aged 3 months to 3 years, the dietary sources of vitamin D and the association between vitamin D intake and sociodemographic factors. Subjects and methods: The subjects are participants in the Finnish Type I Diabetes Prediction and Prevention Nutrition Study born between October 1997 and October 1998. At the age of 3 and 6 months, 1, 2 and 3 years, 342 (72% of the invited families), 298 (63%), 267 (56%), 233 (49%) and 209 (44%) families, respectively, participated in the present study. Food consumption was assessed by a 3-day food record. A structured questionnaire was used to record the parents' socioeconomic status. Results: The mean dietary vitamin D intake exceeded the recommendation (10 mu g/day) at the age of 3 (11.0 mu g) and 6 months (12.0 mu g), but decreased thereafter being 9.8, 5.0 and 4.1 mu g at 1, 2 and 3 years of age, respectively. Among the children 91, 91, 81, 42 and 26% used vitamin D supplements at the age of 3 and 6 months, and 1, 2 and 3 years, respectively. In children not using vitamin D supplements, vitamin D intake was less than 10 mg/day at all ages. Vitamin D intake from food did not differ in children who used and did not use vitamin D supplements. Vitamin D supplements were the main source of vitamin D intake in all age groups studied, followed by vitamin D-fortified infant formula in 3-month-olds and infant formula and baby foods in 6-month-olds. After the age of 1 year, the most important food sources of vitamin D were margarine, fish, baby foods, low-fat milk and eggs. Sociodemographic factors, especially the number of children in the family and maternal age, were associated with the total vitamin D intake and vitamin D supplement use. Conclusion: Vitamin D supplements are not used according to the dietary recommendations in a substantial proportion of Finnish children.
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| 4. |
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| 5. |
- Virtanen, S. M., et al.
(author)
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Age at introduction of new foods and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes
- 2006
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In: Diabetologia. - Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki 00300, Finland. Tampere Univ, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Res Unit, Tampere, Finland. London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, Med Stat Unit, London WC1, England. Finnish Canc Registry, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. : SPRINGER. - 0012-186X .- 1432-0428. ; 49:7, s. 1512-1521
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Evidence for the role of infant feeding in the development of beta cell autoimmunity is inconsistent. We set out to study the effects of breastfeeding and of age at introduction of supplementary foods on the development of beta cell autoimmunity. Subjects and methods: A prospective birth cohort of 3,565 infants with HLA-DQB1-conferred susceptibility to type 1 diabetes was recruited between 1996 and 2001 from two university hospital areas in Finland. Blood samples were collected at 3- to 12-month intervals to measure antibodies against islet cells, insulin, glutamate dehydroxylase and islet antigen 2. The families kept a record on the age at introduction of new foods, and for each visit completed a structured dietary questionnaire. The endpoint was repeated positivity for islet cell antibodies together with at least one of the other three antibodies. Results: The overall or exclusive duration of breastfeeding was not associated with the risk of developing the endpoint. An early age at introduction of fruits and berries (<= 4 months) was related to increased risk of developing positivity for the endpoint (hazard ratio [95% CI] for earliest tertile 2.02 [1.03-3.95] and for midtertile 1.97 [1.06-3.64] compared with latest tertile > 4 months). Also, introducing roots between 3 and 3.9 months (midtertile) was related to increased risk of the endpoint (hazard ratio [95% CI] for the earliest tertile 1.04 [0.57-1.90] and for midtertile 1.82 [1.19-2.79] compared with latest tertile). These associations were independent of several putative socio-demographic and perinatal confounding factors. Conclusions/interpretation: Our findings suggest that an early age at introduction of fruits and berries and roots associates independently with beta cell autoimmunity, contradicting earlier findings from smaller birth cohort studies.
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| 6. |
- Hakola, L., et al.
(author)
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Maternal fatty acid intake during pregnancy and the development of childhood overweight : a birth cohort study
- 2017
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In: Pediatric Obesity. - : WILEY. - 2047-6302 .- 2047-6310. ; 12, s. 26-37
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Journal article (peer-reviewed)abstract
- BackgroundMaternal diet during pregnancy may contribute to the risk of offspring adiposity. ObjectivesThe objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7years. MethodsIn a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. ResultsIn girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p=0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid+eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p=0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. ConclusionsMaternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Sumnik, Z., et al.
(author)
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Persistent heterogeneity in diabetes technology reimbursement for children with type 1 diabetes: The SWEET perspective
- 2019
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 20:4, s. 434-443
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Journal article (peer-reviewed)abstract
- Background: Frequent use of modern diabetes technologies increases the chance for optimal type 1 diabetes (T1D) control. Limited reimbursement influences the access of patients with T1D to these modalities and could worsen their prognosis. We aimed to describe the situation of reimbursement for insulins, glucometers, insulin pumps (CSII) and continuous glucose monitoring (CGM) for children with T1D in European countries participating in the SWEET Project and to compare data from EU countries with data from our previous study in 2009. Methods: The study was conducted between March 2017 and August 2017. First, we approached diabetes technology companies with a survey to map the reimbursement of insulins and diabetic devices. The data collected from these companies were then validated by members of the SWEET consortium. Results: We collected data from 29 European countries, whereas all types of insulins are mostly fully covered, heterogeneity was observed regarding the reimbursement of strips for glucometers (from 90 strips/month to no limit). CSII is readily available in 20 of 29 countries. Seven countries reported significant quota issues or obstacles for CSII prescription, and two countries had no CSII reimbursement. CGM is at least partially reimbursed in 17 of 29 countries. The comparison with the 2009 study showed an increasing availability of CSII and CGM across the EU. Conclusions: Although innovative diabetes technology is available, a large proportion of children with T1D still do not benefit from it due to its limited reimbursement. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 17. |
- Aittoniemi, J, et al.
(author)
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Relation among mannose-binding lectin 2 genotype, β-cell autoantibodies, and risk for type 1 diabetes in Finnish children
- 2008
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In: Human Immunology. - : Elsevier BV. - 0198-8859 .- 1879-1166. ; 69:2, s. 108-111
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Journal article (peer-reviewed)abstract
- Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial. We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of β-cell autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the biallelic variant genotype reflecting total MBL deficiency tested positive more frequently for ≥3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28, p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D. The association of the biallelic variant genotype with positivity for multiple autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency. © 2008 American Society for Histocompatibility and Immunogenetics.
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| 18. |
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| 19. |
- Haghighi, Mona, et al.
(author)
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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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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)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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| 23. |
- McGlinchey, Aidan J, 1984-, et al.
(author)
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Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes
- 2020
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 143
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Journal article (peer-reviewed)abstract
- In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.
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| 24. |
- Nucci, Anita M., et al.
(author)
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Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk
- 2021
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In: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 64:4, s. 826-835
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Journal article (peer-reviewed)abstract
- Aims/hypothesis We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes. Methods Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10-14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05. Results In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2-10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling. Conclusions/interpretation In children at genetic risk of type 1 diabetes, being overweight at 2-10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes. Graphical abstract
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| 25. |
- Pacaud, Daniele, et al.
(author)
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Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes
- 2021
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In: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 64, s. 119-128
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Journal article (peer-reviewed)abstract
- Aims/hypothesis The aim of this work was to examine the relationship between family history of type 1 diabetes, birthweight, growth during the first 2 years and development of multiple beta cell autoantibodies in children with a first-degree relative with type 1 diabetes and HLA-conferred disease susceptibility. Methods In a secondary analysis of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), clinical characteristics and development of beta cell autoantibodies were compared in relation to family history of type 1 diabetes (mother vs father vs sibling) in 2074 children from families with a single affected family member. Results Multiple autoantibodies (>= 2 of 5 measured) developed in 277 (13%) children: 107 (10%), 114 (16%) and 56 (18%) born with a mother, father or sibling with type 1 diabetes, respectively (p < 0.001). The HR for time to multiple autoimmunity was 0.54 (95% CI 0.39, 0.75) in offspring of affected mothers (n = 107/1046,p < 0.001) and 0.81 (95% CI 0.59, 1.11) (n = 114/722,p = 0.19) in offspring of affected fathers, compared with participants with a sibling with type 1 diabetes (comparator groupn = 56/306). The time to the first autoantibody present (to insulin, GAD, tyrosine phosphatase-related insulinoma-associated 2 molecules, islet cell or zinc transporter 8) was similar in the three groups. Height velocity (zscore/year) in the first 24 months was independently associated with developing multiple antibodies in the total cohort (HR 1.31 [95% CI 1.01, 1.70],p = 0.04). A higher birthweight in children born to an affected mother vs affected father or an affected sibling was not related to the risk of multiple autoimmunity. Conclusions/interpretation The risk of developing multiple autoantibodies was lower in children with maternal type 1 diabetes. For the whole group, this risk of developing multiple autoantibodies was independent of birthweight but was greater in those with increased height velocity during the first 2 years of life. However, the risk associated with paternal type 1 diabetes was not linked to differences in birthweight or early growth.
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| 26. |
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| 27. |
- Vaarala, Outi, 1962-, et al.
(author)
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Insulin treatment in patients with type 1 diabetes induces upregulation of regulatory T-cell markers in peripheral blood mononuclear cells stimulated with insulin in vitro
- 2006
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:12, s. 3446-3454
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Journal article (peer-reviewed)abstract
- Patients with type 1 diabetes are treated with daily injections of human insulin, an autoantigen expressed in thymus. Natural CD4+CD25high regulatory T-cells are derived from thymus, and accordingly human insulin-specific regulatory T-cells should exist. We had a chance to study peripheral blood mononuclear cells (PBMCs) from children with type 1 diabetes both before and after starting insulin treatment, and thus we could analyze the effects of insulin treatment on regulatory T-cells in children with type 1 diabetes. PBMCs were stimulated for 72 h with bovine/human insulin. The mRNA expression of regulatory T-cell markers (transforming growth factor-β, Foxp3, cytotoxic T-lymphocyte antigen-4 [CTLA-4], and inducible co-stimulator [ICOS]) or cytokines (γ-interferon [IFN-γ], interleukin [IL]-5, IL-4) was measured by quantitative RT-PCR. The secretion of IFN-γ, IL-2, IL-4, IL-5, and IL-10 was also studied. The expression of Foxp3, CTLA-4, and ICOS mRNAs in PBMCs stimulated with bovine or human insulin was higher in patients on insulin treatment than in patients studied before starting insulin treatment. The insulin-induced Foxp3 protein expression in CD4+CD25 high cells was detectable in flow cytometry. No differences were seen in cytokine activation between the patient groups. Insulin stimulation in vitro induced increased expression of regulatory T-cell markers, Foxp3, CTLA-4, and ICOS only in patients treated with insulin, suggesting that treatment with human insulin activates insulin-specific regulatory T-cells in children with newly diagnosed type 1 diabetes. This effect of the exogenous autoantigen could explain the difficulties to detect in vitro T-cell proliferation responses to insulin in newly diagnosed patients. Furthermore, autoantigen treatment-induced activation of regulatory T-cells may contribute to the clinical remission of the disease. © 2006 by the American Diabetes Association.
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| 29. |
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| 30. |
- Viskari, H, et al.
(author)
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Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies : Time trends and geographical variation
- 2005
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:7, s. 1280-1287
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: We have previously observed an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population. The aim of this study was to analyse whether maternal enterovirus antibody status, which reflects both the frequency of enterovirus infections and the protection conferred by the mother on the offspring, also correlates with the incidence of type 1 diabetes. Methods: Maternal enterovirus antibodies were analysed from serum samples taken from pregnant women between 1983 and 2001 in Finland and Sweden using enzyme immunoassay and neutralisation assays. Comparable samples were also taken between 1999 and 2001 in countries with a lower incidence of diabetes (Estonia, Germany, Hungary, Israel, Lithuania, Russia). Results: A clear decrease was observed in maternal enterovirus antibody levels over the past 20 years (p<0.0001). The frequency of enterovirus antibodies was higher in countries with a low or intermediate incidence of type 1 diabetes compared with high-incidence countries (p<0.0001). Conclusions/interpretation: These findings are in line with our previous observations supporting the hypothesis that a low frequency of enterovirus infection in the background population increases the susceptibility of young children to the diabetogenic effect of enteroviruses. © Springer-Verlag 2005.
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| 31. |
- Akerblom, H.K., et al.
(author)
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Environmental factors in the etiology of type 1 diabetes
- 2002
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In: American Journal of Medical Genetics. - Hoboken, NJ, United States : John Wiley & Sons. - 0148-7299 .- 1096-8628. ; 115:1, s. 18-29
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Research review (peer-reviewed)abstract
- Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes. © 2002 Wiley-Liss, Inc.
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| 32. |
- Arkkola, Tuula, et al.
(author)
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Relationship of maternal weight status and weight gain rate during pregnancy to the development of advanced beta cell autoimmunity in the offspring : a prospective birth cohort study
- 2011
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In: Pediatric Diabetes. - : WILEY. - 1399-543X .- 1399-5448. ; 12:5, s. 478-484
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Journal article (peer-reviewed)abstract
- Objective: This study set out to examine how maternal initial body mass index (BMI) and weight gain during pregnancy associate with advanced beta cell autoimmunity in the offspring. Subjects: A population-based birth cohort of 4093 children with increased human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes (T1D) and their mothers were recruited between 1997 and 2002 in two university hospital regions in Finland. Methods: The children were monitored for T1D-associated autoantibodies at 3- to 12-month intervals. Advanced beta cell autoimmunity was defined as repeated positivity for islet cell antibodies and at least one of the other three autoantibodies (antibodies to insulin, glutamate decarboxylase and islet antigen 2). Mothers were asked to record the results of the weight measurements during their first and last visits to the antenatal clinic. The initial BMI and weight gain rate were calculated for each woman. Results: Altogether, 175 children developed advanced beta cell autoimmunity or T1D during the follow-up. Maternal BMI before pregnancy or weight gain during pregnancy was not associated with the end-point. Maternal vocational education was associated with child's smaller risk of developing advanced beta cell autoimmunity.
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| 33. |
- Battaglia, Manuela, et al.
(author)
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Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
- 2020
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:1, s. 5-12
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Journal article (peer-reviewed)abstract
- The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
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| 34. |
- Greiner, Thomas U., 1977, et al.
(author)
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The Gut Microbiota Modulates Glycaemic Control and Serum Metabolite Profiles in Non-Obese Diabetic Mice
- 2014
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Journal article (peer-reviewed)abstract
- Islet autoimmunity in children who later progress to type 1 diabetes is preceded by dysregulated serum metabolite profiles, but the origin of these metabolic changes is unknown. The gut microbiota affects host metabolism and changes in its composition contribute to several immune-mediated diseases; however, it is not known whether the gut microbiota is involved in the early metabolic disturbances in progression to type 1 diabetes. We rederived non-obese diabetic ( NOD) mice as germ free to explore the potential role of the gut microbiota in the development of diabetic autoimmunity and to directly investigate whether the metabolic profiles associated with the development of type 1 diabetes can be modulated by the gut microbiota. The absence of a gut microbiota in NOD mice did not affect the overall diabetes incidence but resulted in increased insulitis and levels of interferon gamma and interleukin 12; these changes were counterbalanced by improved peripheral glucose metabolism. Furthermore, we observed a markedly increased variation in blood glucose levels in the absence of a microbiota in NOD mice that did not progress to diabetes. Additionally, germ-free NOD mice had a metabolite profile similar to that of pre-diabetic children. Our data suggest that germ-free NOD mice have reduced glycaemic control and dysregulated immunologic and metabolic responses.
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| 35. |
- Hirvonen, M Karoliina, et al.
(author)
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Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes
- 2023
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.
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| 36. |
- Knip, Mikael, et al.
(author)
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Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
- 2018
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In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:1, s. 38-48
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Journal article (peer-reviewed)abstract
- IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
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| 37. |
- Knip, Mikael, et al.
(author)
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Hydrolyzed infant formula and early β-cell autoimmunity : a randomized clinical trial.
- 2014
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:22, s. 2279-2287
-
Journal article (peer-reviewed)abstract
- IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.
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| 38. |
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| 39. |
- Kostic, Aleksandar D., et al.
(author)
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The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes
- 2015
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In: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 17:2, s. 260-273
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Journal article (peer-reviewed)abstract
- Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.
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| 40. |
- Lamichhane, Santosh, et al.
(author)
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Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children
- 2023
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In: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 14
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody).METHODS: Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites.RESULTS: We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP.CONCLUSION/INTERPRETATION: Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.
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| 41. |
- Lamichhane, Santosh, et al.
(author)
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Cord-Blood Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes
- 2019
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In: Biomolecules. - : MDPI. - 2218-273X. ; 9:1
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Journal article (peer-reviewed)abstract
- Previous studies suggest that children who progress to type 1 diabetes (T1D) later in life already have an altered serum lipid molecular profile at birth. Here, we compared cord blood lipidome across the three study groups: children who progressed to T1D (PT1D; n = 30), children who developed at least one islet autoantibody but did not progress to T1D during the follow-up (P1Ab; n = 33), and their age-matched controls (CTR; n = 38). We found that phospholipids, specifically sphingomyelins, were lower in T1D progressors when compared to P1Ab and the CTR. Cholesterol esters remained higher in PT1D when compared to other groups. A signature comprising five lipids was predictive of the risk of progression to T1D, with an area under the receiver operating characteristic curve (AUROC) of 0.83. Our findings provide further evidence that the lipidomic profiles of newborn infants who progress to T1D later in life are different from lipidomic profiles in P1Ab and CTR.
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| 42. |
- Lamichhane, Santosh, et al.
(author)
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Dysregulation of secondary bile acid metabolism precedes islet autoimmunity and type 1 diabetes
- 2022
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In: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 3:10
-
Journal article (peer-reviewed)abstract
- The gut microbiota is crucial in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to type 1 diabetes (T1D). Here, we analyzed serum and stool BAs in longitudinal samples collected at 3, 6, 12, 18, 24, and 36 months of age from children who developed a single islet autoantibody (AAb) (P1Ab; n = 23) or multiple islet AAbs (P2Ab; n = 13) and controls (CTRs; n = 38) who remained AAb negative. We also analyzed the stool microbiome in a subgroup of these children. Factor analysis showed that age had the strongest impact on both BA and microbiome profiles. We found that at an early age, systemic BAs and microbial secondary BA pathways were altered in the P2Ab group compared with the P1Ab and CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.
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| 43. |
- Lamichhane, Santosh, et al.
(author)
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Exposure to per- and polyfluoroalkyl substances associates with an altered lipid composition of breast milk
- 2021
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 157
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Journal article (peer-reviewed)abstract
- The composition of human breast milk is highly variable inter- and intra-individually. Environmental factors are suspected to contribute to such compositional variation, however, their impact on breast milk composition is currently poorly understood. We sought to (1) define the impact of maternal exposure to per- and polyfluoroalkyl substances (PFAS) on lipid composition of human breast milk, and (2) to study the combined impact of maternal PFAS exposure and breast milk lipid composition on the growth of the infants.In a mother-infant study (n = 44) we measured the levels of PFAS and lipids in maternal serum and conducted lipidomics analysis of breast milk collect 2-4 days after the delivery and at 3 months of infant age, by using ultra high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry. Gastrointestinal biomarkers fecal calprotectin and human beta defensin 2 were measured in the stool samples at the age of 3, 6, 9, and 12 months. Maternal diet was studied by a validated food frequency questionnaire. PFAS levels were inversely associated with total lipid levels in the breast milk collected after the delivery. In the high exposure group, the ratio of acylated saturated and polyunsaturated fatty acids in triacylglycerols was increased. Moreover, high exposure to PFAS associated with the altered phospholipid composition, which was indicative of unfavorable increase in the size of milk fat globules. These changes in the milk lipid composition were further associated with slower infant growth and with elevated intestinal inflammatory markers. Our data suggest that the maternal exposure to PFAS impacts the nutritional quality of the breast milk, which, in turn, may have detrimental impact on the health and growth of the children later in life.
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| 44. |
- Lamichhane, Santosh, et al.
(author)
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Impact of Extensively Hydrolyzed Infant Formula on Circulating Lipids During Early Life
- 2022
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In: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
-
Journal article (peer-reviewed)abstract
- Background: Current evidence suggests that the composition of infant formula (IF) affects the gut microbiome, intestinal function, and immune responses during infancy. However, the impact of IF on circulating lipid profiles in infants is still poorly understood. The objectives of this study were to (1) investigate how extensively hydrolyzed IF impacts serum lipidome compared to conventional formula and (2) to associate changes in circulatory lipids with gastrointestinal biomarkers including intestinal permeability.Methods: In a randomized, double-blind controlled nutritional intervention study (n = 73), we applied mass spectrometry-based lipidomics to analyze serum lipids in infants who were fed extensively hydrolyzed formula (HF) or conventional, regular formula (RF). Serum samples were collected at 3, 9, and 12 months of age. Child's growth (weight and length) and intestinal functional markers, including lactulose mannitol (LM) ratio, fecal calprotectin, and fecal beta-defensin, were also measured at given time points. At 3 months of age, stool samples were analyzed by shotgun metagenomics.Results: Concentrations of sphingomyelins were higher in the HF group as compared to the RF group. Triacylglycerols (TGs) containing saturated and monounsaturated fatty acyl chains were found in higher levels in the HF group at 3 months, but downregulated at 9 and 12 months of age. LM ratio was lower in the HF group at 9 months of age. In the RF group, the LM ratio was positively associated with ether-linked lipids. Such an association was, however, not observed in the HF group.Conclusion: Our study suggests that HF intervention changes the circulating lipidome, including those lipids previously found to be associated with progression to islet autoimmunity or overt T1D.Clinical Trial Registration: [Clinicaltrials.gov], identifier [NCT01735123].
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| 45. |
- Lehtonen, Eveliina, et al.
(author)
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Use of vitamin D supplements during infancy in an international feeding trial.
- 2014
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In: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 17:4, s. 810-22
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.DESIGN: Longitudinal study.SETTING: Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.SUBJECTS: Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.RESULTS: Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80% of the infants), with somewhat lower rates observed in Southern Europe (> 60%). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g., 71% v. 44% at 6 months of age). Less than 2% of infants in the U.S.A. and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.CONCLUSIONS: Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the U.S.A. and Australia very few were given supplementation.
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| 46. |
- Lumia, Mirka, et al.
(author)
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Food consumption and risk of childhood asthma
- 2015
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In: Pediatric Allergy and Immunology. - : WILEY. - 0905-6157 .- 1399-3038. ; 26:8, s. 789-796
-
Journal article (peer-reviewed)abstract
- BackgroundThe consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM)-free diet) in early life and the risk of atopic and non-atopic asthma. MethodsFood intake of 182 children with asthma and 728 matched controls was measured using 3-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. ResultsThe diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at 4yr of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. ConclusionsDietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk.
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| 47. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Journal article (peer-reviewed)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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| 48. |
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| 49. |
- Nwaru, Bright I, 1978, et al.
(author)
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Vitamin D intake during the first 4years and onset of asthma by age 5: A nested case-control study.
- 2017
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In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; , s. 1-8
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Journal article (peer-reviewed)abstract
- Early-life vitamin D intake has been linked to asthma risk in childhood, but the role of longitudinal vitamin D exposure has not been previously evaluated. We investigated the association between vitamin D intake during the first 4years of life and asthma risk by age 5.Within a Finnish population-based birth cohort, 182 incident asthma cases were matched to 728 controls on sex, genetic risk for type 1 diabetes, delivery hospital, and time of birth. Vitamin D intake was assessed by age-specific 3day food records. Parents completed a validated version of the International Study of Asthma and Allergies in Childhood questionnaire at 5years.At 3months, supplements were the main source of vitamin D intake; intake from foods increased from 3months on, mainly from fortified milk products. Vitamin D intake at each specific age was associated with an increased risk of any asthma, atopic, and non-atopic asthma, but only intake at 1 and 2years was statistically significantly associated with asthma. Longitudinal vitamin D intake was associated with an increased risk of asthma (OR 1.24; 95%CI 1.00-1.53).Increased vitamin D intake in childhood, particularly intake at 1 and 2years of age, may increase risk of childhood asthma. This might reflect a true effect or residual confounding by lifestyle or environmental factors. Repeated assessment of vitamin D intake allowed evaluation of the longitudinal and age-dependent impact of vitamin D on the risk of asthma. Further longitudinal studies are required to confirm or question these findings.
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| 50. |
- Ojwang', Vincent, et al.
(author)
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Early exposure to cats, dogs and farm animals and the risk of childhood asthma and allergy.
- 2020
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In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 31:3, s. 265-272
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Journal article (peer-reviewed)abstract
- Synergistic role of exposure to cats, dogs, and farm animals during infancy on the risk of childhood asthma and allergy remains unknown.To investigate independent and synergistic associations between exposure to indoor pets and farm animals during infancy and the risk of asthma and allergy by age 5.We studied 3781 children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) nutrition study. At age 5, a validated version of the International Study of Asthma and Allergies in Childhood questionnaire was administered to collect information on asthma and allergic disease; and exposure to indoor pets and farm animals during the first year of life. Allergen-specific IgE antibodies were analyzed from serum samples. Statistical analyses employed Cox proportional hazards- and logistic regression.Having a dog in the house was inversely associated with the risk of asthma (HR 0.60; 95%CI, 0.38-0.96); allergic rhinitis (OR 0.72; 95%CI, 0.53-0.97); and atopic sensitization (OR 0.77; 95%CI, 0.63-0.96). Having a cat was associated with decreased risk of atopic eczema (OR 0.68; 95%CI, 0.51-0.92). Farm animals were neither independently nor in synergy with indoor pets associated with the outcomes.Having a dog or cat in the house during the first year of life may protect against childhood asthma and allergy. We did not find a synergistic association between cat, dog and farm animal exposure on the risk of childhood asthma and allergy. Future research should identify specific causative exposures conferred by indoor pets and whether they could be recommended for allergy prevention.
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