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Objective: To assess milk feeding on the maternity ward and during infancy, and their relationship to sociodemographic determinants. The validity of our 3-month questionnaire in measuring hospital feeding was assessed.Design: A prospective Finnish birth cohort with increased risk to type 1 diabetes recruited between 1996 and 2004. The families completed a follow-up form on the age at introduction of new foods and age-specific dietary questionnaires.Setting: Type 1 Diabetes Prediction and Prevention (DIPP) project, Finland.Subjects: A cohort of 5993 children (77 % of those invited) participated in the main study, and 117 randomly selected infants in the validation study.Results: Breast milk was the predominant milk on the maternity ward given to 99 % of the infants. Altogether, 80 % of the women recalled their child being fed supplementary milk (donated breast milk or infant formula) on the maternity ward. The median duration of exclusive breast-feeding was 1.4 months (range 0-8) and that of total breast-feeding 7.0 months (0-25). Additional milk feeding on the maternity ward, short parental education, maternal smoking during pregnancy, small gestational age and having no siblings were associated with a risk of short duration of both exclusive and total breast-feeding. In the validation study, 78 % of the milk types given on the maternity ward fell into the same category, according to the questionnaire and hospital records.Conclusions: The recommendations for infant feeding were not achieved. Infant feeding is strongly influenced by sociodemographic determinants and feeding practices on the maternity wards. Long-term breast-feeding may be supported by active promotion on the maternity ward. [ABSTRACT FROM AUTHOR]

The evidence of the effect of the age at introduction of new foods during infancy on the development of asthma and allergic rhinitis is inconsistent and scarce. We set out to study these associations. A prospective birth cohort of infants with increased HLA-DQB1-conferred risk for type 1 diabetes was recruited in 1996-2000. The families completed at home a record on the age at introduction of new foods. Persistent asthma and allergic rhinitis were assessed at the age of 5 years with an International Study of Asthma and Allergies in Childhood-type questionnaire. The Cox proportional hazards regression analyses were adjusted for parental asthma and allergic diseases, and several perinatal and sociodemographical factors. Out of the 1293 children, 77 (6.0%) developed persistent asthma; and out of the 1288 children, 185 (14.4%) developed allergic rhinitis by the age of 5 years. Early age at introduction of oats was associated with a reduced risk of persistent asthma (hazard ratio (HR; 95% CI) for the first and mid-tertiles compared with the latest tertile was 0.36 (0.15, 0.85) and 0.37 (0.22, 0.62), respectively, P < 0.001). Early age at introduction of fish was dose dependently associated with a decreased risk of allergic rhinitis (HR (95% CI) for the first and mid-tertiles compared with the latest tertile was 0.34 (0.22, 0.54) and 0.45 (0.28, 0.70), respectively, P < 0.001). The present finding that age at introduction of oats is inversely and independently associated with development of persistent asthma is novel. We confirmed the earlier observation that the age at introduction of fish is inversely related to the risk of allergic rhinitis. Clinical implications remain to be determined. [ABSTRACT FROM AUTHOR]

Background: Early exposure to cow's milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective: We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods: We studied a subgroup of 94 children randomized to be weaned to a CM-based infant formula in the trial to reduce insulin-dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen-conferred T1D susceptibility and had an affected first-degree relative. After 7 years of follow-up, 8 subjects had progressed to T1D, 15 had at least one disease-associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta-lactoglobulin (BLG), bovine serum albumin, and alpha-casein and IgG antibodies to bovine insulin (BI) were measured with enzyme-linked immunosorbent assays from sequential samples. Results: The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody-positive subjects than in autoantibody-negative subjects at 18 months of age (p = 0.022). Conclusion: An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D. [ABSTRACT FROM AUTHOR]

BACKGROUND: Type 1 diabetes may have its origins in the fetal period of life. Free radicals were implicated in the cause of type 1 diabetes. It was hypothesized that antioxidant nutrients could protect against type 1 diabetes. OBJECTIVE: We assessed whether high maternal intake of selected dietary antioxidants during pregnancy is associated with a reduced risk of advanced beta cell autoimmunity in the child, defined as repeated positivity for islet cell antibodies plus >/=1 other antibody, overt type 1 diabetes, or both. DESIGN: The study was carried out as part of the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention Project. The data comprised 4297 children with increased genetic susceptibility to type 1 diabetes, born at the University Hospital of Oulu or Tampere, Finland, between October 1997 and December 2002. The children were monitored for diabetes-associated autoantibodies from samples obtained at 3-12-mo intervals. Maternal antioxidant intake during pregnancy was assessed postnatally with a self-administered food-frequency questionnaire, which contained a question about consumption of dietary supplements. RESULTS: Maternal intake of none of the studied antioxidant nutrients showed association with the risk of advanced beta cell autoimmunity in the child. The hazard ratios, indicating the change in risk per a 2-fold increase in the intake of each antioxidant, were nonsignificant and close to 1. CONCLUSION: High maternal intake of retinol, beta-carotene, vitamin C, vitamin E, selenium, zinc, or manganese does not protect the child from development of advanced beta cell autoimmunity in early childhood. Copyright © 2008 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Objectives: To identify and describe dietary patterns in a cohort of pregnant women and investigate whether the dietary patterns are associated with dietary intake and sociodemographic factors.Design: Mothers entering the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study in 1997-2002 were retrospectively asked to complete a food-frequency questionnaire concerning their diet during pregnancy. Principal components analysis was used to identify dietary patterns.Setting: Finland.Subjects: Subjects were 3730 women with a newborn infant carrying increased genetic susceptibility to type 1 diabetes mellitus.Results: Seven factors were identified and named. Energy intake correlated positively with 'Healthy', 'Fast food', 'Traditional bread', 'Traditional meat' and 'Coffee' patterns and inversely with the 'Alcohol and butter' pattern. Intake of dietary fibre correlated positively with 'Healthy', 'Traditional bread' and 'Low-fat foods' patterns and inversely with the 'Alcohol and butter' pattern. The seven dietary patterns seemed to account for relatively large proportions of the variance in energy and nutrient intakes except for the intake of vitamin D, vitamin C, carotenoids and calcium. Maternal age and higher level of education were associated with higher scores on 'Healthy', 'Low-fat foods' and 'Alcohol and butter' patterns.Conclusion: Principal components analysis produced seven dietary patterns which may be useful for further research concerning maternal diet and health outcomes among both mothers and their offspring. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed at evaluating the relationship between the circulating concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and sL-selectin and the appearance of beta-cell autoimmunity, and at assessing whether these molecules could assist in the identification of environmental factors implicated in the immune process damaging the pancreatic beta-cells. METHODS: Serum levels of soluble adhesion molecules were measured with enzyme-linked immunosorbent assays over the first 2 years of life in 65 children seroconverting to positivity for autoantibodies and 65 control children, all with HLA-conferred susceptibility to type 1 diabetes (T1D). RESULTS: The total integrated concentrations of soluble adhesion molecules were comparable between the two groups. The autoantibody-positive children tended to have higher sL-selectin concentrations during the 3-month seroconversion (SC) period than did the control children during the corresponding period (P = 0.07), the difference being significant (P = 0.03) after excluding subjects with signs of a concurrent enterovirus infection. Autoantibody-positive children had higher concentrations of sL-selectin in the 3-month period when an enterovirus infection was detectable than did the control children (P = 0.018). No significant difference could, however, be seen after excluding the children with concomitant seroconversion to autoantibody positivity. CONCLUSIONS: Elevated concentrations of sL-selectin are temporally associated with seroconversion to autoantibody positivity suggesting that leukocyte activation might coincide with the appearance of beta-cell autoimmunity. Early-onset progressive beta-cell autoimmunity, on the other hand, is not reflected in overall increased concentrations of soluble adhesion molecules in the peripheral circulation during the first 2 years of life in children carrying increased HLA-conferred disease susceptibility. Enterovirus infections (EVIs) are not independently associated with increased circulating sL-selectin concentrations in young children with enhanced HLA-conferred susceptibility to T1D. [ABSTRACT FROM AUTHOR]

Objective: To generate predictive models for the assessment of risk of type 1 diabetes and age at diagnosis in siblings of children with newly diagnosed type 1 diabetes.Research Design and Methods: Cox regression analysis was used to assess the risk of progression to type 1 diabetes, and multiple regression analysis was used to estimate the age at disease presentation in 701 siblings of affected children. Sociodemographic, genetic, and immunological variables were included in the analyses. Subanalyses were performed in a group of 77 autoantibody-positive siblings with additional metabolic data.Results: A total of 47 siblings (6.7%) presented with type 1 diabetes during the 15-year observation period. Young age, an increasing number of detectable diabetes-associated autoantibodies at initial sampling and of affected first-degree relatives, and HLA DR-conferred disease susceptibility predicted progression to type 1 diabetes. In the subgroup of 77 autoantibody-positive siblings, young age, HLA DR-conferred susceptibility, an increasing number of autoantibodies, a reduced first-phase insulin response, and decreased insulin sensitivity in relation to first-phase insulin response were associated with increased risk of progression to type 1 diabetes. Age at diagnosis was predicted by age, insulinoma-associated protein 2 antibody levels, and number of autoantibodies at initial sampling (R(2) = 0.76; P < 0.001). In the smaller cohort of autoantibody-positive subjects, first-phase insulin response and HLA DR-conferred susceptibility were additional predictors of age at diagnosis.Conclusions: Information on autoantibody status and levels, HLA-conferred disease susceptibility, and insulin secretion and sensitivity seems to be useful in addition to age and family history of type 1 diabetes when assessing risk of progression to type 1 diabetes and time to diagnosis in siblings of children with newly diagnosed type 1 diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Type 1 diabetes is characterised by familial aggregation. We set out to explore whether beta-cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering. METHODS: Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families. When a child tested positive for ICA, all his/her previous or subsequent samples that were available were also tested for insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to the IA-2 protein (IA-2A). RESULTS: Forty-four families were observed to have two or more children positive for at least ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p < 0.001). The frequency of multiple (>/=2) autoantibodies also showed familial aggregation, the observed proportion (0.39%) being three times that expected (0.13%; p < 0.001). In 72.7% of the families with at least two ICA-positive siblings, the children with autoantibodies had the same HLA DQB1 genotype. The median age difference between the ICA-positive children within the same family was 3.3 years (range 0.0-10.5 years), and the median time interval in the appearance of ICA within the family was 1.6 years (range 0.0-3.2). CONCLUSIONS: beta-cell autoimmunity, as defined by the appearance of ICA, demonstrates familial aggregation, although the antibodies do not appear in close temporal proximity or at an identical age within the same family. The HLA-DQB1 genotypes are more often identical in siblings with autoantibodies than in other siblings. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is an immune-mediated disease characterized by a preclinical prodrome during which beta cell autoimmunity proceeds at a variable rate. Large geographic differences and a conspicuous increase in incidence, especially among young children since the 1950s, and the relatively low concordance in identical twins are factors that favor a critical role of environmental factors in the etiology of this disease. Only approximately 5% or fewer subjects with HLA-conferred genetic susceptibility to type 1 diabetes actually develop the clinical disease. Breastfeeding, nicotinamide, zinc, and vitamins C, D, and E have been reported as possibly protecting against type 1 diabetes, whereas N-nitroso compounds, cow milk, increased linear growth, and obesity may increase the risk. Thus far, only the significance of infant feeding, cow milk, and vitamin D have been studied in both case-control and cohort settings. The major shortcoming of most studies done so far is that only single dietary exposures have been assessed at single time points. Putative nutritional and other confounding factors have received little attention as have the limitations of the dietary methods used. There is little firm evidence of the significance of nutritional factors in the etiology of type 1 diabetes. The availability of good markers of preclinical type 1 diabetes and of genetic risk have decreased the sample sizes needed and made longitudinal cohort studies of the assessment of children's diets feasible. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Objective: To study cross-sectional associations of dietary fiber intake with insulin resistance, insulin secretion, and glucose tolerance in a population at high risk for type 2 diabetes.Research Design and Methods: The subjects consisted of 248 male and 304 female adult nondiabetic relatives of patients with type 2 diabetes. Dietary intake was measured by means of two 3-day food records. Associations of total, water-insoluble, and water-soluble fiber with measures of glucose metabolism based on an oral glucose tolerance test, were analyzed by multiple linear regression analysis adjusting for sex, age, length of education, physical activity, BMI, waist-to-hip ratio, systolic blood pressure, and serum triglyceride and HDL cholesterol concentrations. The homeostasis model assessment insulin resistance index, the incremental 30-min serum insulin concentration divided by the incremental 30-min glucose concentration, and fasting and 2-h glucose concentrations were the outcome variables.Results: The dietary intake of total as well as water-insoluble and water-soluble fiber was inversely associated with insulin resistance: -0.17 (0.07), P = 0.012; -0.15 (0.07), P = 0.024; and -0.14 (0.07), P = 0.049 [regression coefficients (SE)]. Fiber variables were unrelated to insulin secretion and plasma glucose concentrations.Conclusions: The results support evidence that a high intake of dietary fiber is associated with enhanced insulin sensitivity and therefore may have a role in the prevention of type 2 diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The role of antioxidants in the pathogenesis of type 2 diabetes is uncertain. OBJECTIVE: We evaluated cross-sectional relations of dietary intakes and plasma concentrations of antioxidants with glucose metabolism in a high-risk population. DESIGN: The subjects were 81 male and 101 female first- and second-degree, nondiabetic relatives of patients with type 2 diabetes. Antioxidant intake data were based on 3-d food records. Subjects taking supplements containing beta-carotene or alpha-tocopherol were excluded. Plasma antioxidant concentrations were measured by HPLC. By using multiple linear regression analysis and adjusting for demographic, anthropometric, and lifestyle covariates, we studied whether dietary and plasma alpha- and beta-carotene, lycopene, and alpha- and gamma-tocopherol were related to fasting and 2-h concentrations of glucose and nonesterified fatty acids during an oral-glucose-tolerance test, to the homeostasis model assessment index of insulin resistance, and to measures of beta cell function (incremental 30-min serum insulin concentration during an oral-glucose-tolerance test and first-phase insulin secretion during an intravenous-glucose-tolerance test). RESULTS: In men, dietary carotenoids were inversely associated with fasting plasma glucose concentrations (P < 0.05), plasma beta-carotene concentrations were inversely associated with insulin resistance (P = 0.003), and dietary lycopene was directly related to baseline serum concentrations of nonesterified fatty acids (P = 0.034). In women, dietary alpha-tocopherol and plasma beta-carotene concentrations were inversely and directly associated, respectively, with fasting plasma glucose concentrations (P < 0.05). In both sexes, cholesterol-adjusted alpha-tocopherol concentrations were directly associated with 2-h plasma glucose concentrations (P < 0.05). CONCLUSION: The data suggest an advantageous association of carotenoids, which are markers of fruit and vegetable intake, with glucose metabolism in men at high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is considered to be a T-cell-mediated autoimmune disease in which insulin-producing beta-cells are destroyed. Immunity to insulin has been suggested to be one of the primary autoimmune mechanisms leading to islet cell destruction. We have previously shown that the first immunization to insulin occurs by exposure to bovine insulin (BI) in cow's milk (CM) formula. In this study, we analyzed the development of insulin-specific T-cell responses by proliferation test, emergence of insulin-binding antibodies by enzyme immunoassay, and insulin autoantibodies by radioimmunoassay in relation to CM exposure and family history of type 1 diabetes in infants with a first-degree relative with type 1 diabetes and increased genetic risk for the disease. The infants were randomized to receive either an adapted CM-based formula or a hydrolyzed casein (HC)-based formula after breast-feeding for the first 6-8 months of life. At the age of 3 months, both cellular and humoral responses to BI were higher in infants exposed to CM formula than in infants fully breast-fed (P = 0.015 and P = 0.007). IgG antibodies to BI were higher in infants who received CM formula than in infants who received HC formula at 3 months of age (P = 0.01), but no difference in T-cell responses was seen between the groups. T-cell responses to BI at 9 months of age (P = 0.05) and to human insulin at 12 (P = 0.014) and 24 months of age (P = 0.009) as well as IgG antibodies to BI at 24 months of age (P = 0.05) were lower in children with a diabetic mother than in children with a diabetic father or a sibling, suggesting possible tolerization to insulin by maternal insulin therapy. The priming of insulin-specific humoral and T-cell immunity occurs in early infancy by dietary insulin, and this phenomenon is influenced by maternal type 1 diabetes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the prevalence and determinants of self-reported neck or shoulder pain (NSP) and low back pain (LBP) among 12-18-year-olds. A questionnaire was mailed to a nationally representative sample of 11,276 12-, 14-, 16- and 18-year-olds in 1991. The response rate was 77%. NSP was perceived at least once a week by 15% of 12-18-year-olds and LBP by 8%. Both symptoms were more prevalent among girls than among boys, and the prevalence increased with age. Among the determinants investigated, the number of perceived psychosomatic symptoms had the strongest association with NSP and LBP. Our study confirmed the co-morbidity of NSP and LBP, and indicated that NSP is more frequent than believed among 16-18-year-old girls. The strong association of psychosomatic symptoms with NSP and LBP suggests that the latter two pain states could be more psychosomatic than nosiceptive in character. [ABSTRACT FROM AUTHOR]

The food consumption of 38 children newly diagnosed with diabetes aged < 6 years at diagnosis was assessed by 5 day food records. During the 2 year follow up, the proportion of the total energy intake made up of protein decreased from 20% to 18%, that of carbohydrates from 54% to 52%, and that of fat increased from 26% to 30%. The energy intake from sucrose (3%) did not change. In addition, There was a small decrease in the intake of fibre and several vitamins and minerals. One year after diagnosis, the diet of diabetic children was compared with that of 66 age, sex, and social status matched control children. More energy was derived from protein (19% v 15%) and carbohydrates (53% v 50%), and less from fat (28% v 35%), especially from saturated fatty acids (11% v 15%), and sucrose (3% v 16%) in the diet of children with diabetes compared with that of control children. The higher intakes of several vitamins and minerals reflected the higher nutrient density of the diet of children with diabetes. Therefore, the diet of young children with diabetes met the dietary recommendations for subjects with diabetes. Only the protein content of the diet was higher than necessary. [ABSTRACT FROM AUTHOR]

Background: The infant gut microbiome undergoes rapid changes in the first year of life, supporting normal development and long-term health. While diet shapes this process, the role of fibers in complementary foods on gut microbiome maturation is poorly understood., Objectives: We explored how the transition from human milk to fibers in complementary foods shapes the taxonomic and functional maturation of the gut microbiome within the first year of life., Methods: We assessed the longitudinal and cross-sectional development of infant gut microbiomes (N=68 infants) and metabolomes (N=33 infants) using linear mixed models to uncover their associations to dietary fibers and their food sources. Fiber intakes were assessed with 3-day food records (months 3,6,9,12) relying on CODEX-compliant fiber fraction values, and questionnaires tracked the overall complementary food introduction. Bacterial species were identified and quantified via MetaPhlAn2 from metagenomic data, and metabolomic profiles were obtained using four LC-MS methods., Results: We identified 176 complementary food fiber-bacterial species associations. First plant-based fibers associated to microbiota compositions similar to breastfeeding, and further associated with aromatic amino acid metabolites, including 5-hydroxyindoleacetic acid (Total dietary fiber - Complementary foods (g) - β=3.50, CI 2.48-4.52, p=6.53x10-5). Distinct fibers from different food categories showed unique associations with specific bacterial taxa. Key species such as Faecalibacterium prausnitznii, associated with oat fibers (g/MJ, β=2.18, CI 1.36-2.84, p=6.12x10-6), reflective of maturing microbial communities. Fiber intake during weaning associated with shifts in metabolite profiles, including immunomodulatory metabolites, with fiber effects observed in a source- and timing-dependent manner, implicated in gradual microbiome diversification., Conclusions: Introducing complementary dietary fibers during the weaning period supports gut microbiome diversification and stabilization. Even minor dietary variations showed significant associations with microbial taxa and functions from the onset of weaning, highlighting the importance of infant dietary recommendations that support the gut microbiome maturation during early life., Clinical Trial Registration Number: Clinicaltrials.gov Identifier: NCT01735123. Date of registration: November 24, 2012. https://www., Clinicaltrials: gov/ct2/show/NCT01735123., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mikael Knip reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Mikael Knip reports financial support was provided by National Institutes of Health (1DP3DK094338-01). Mikael Knip reports financial support was provided by the Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-17 (250114). Mikael Knip reports financial support was provided by the Medical Research Funds, Tampere and Helsinki University Hospitals. Tommi Vatanen reports was provided by The startup funding from the Helsinki Institute of Life Science, University of Helsinki. Tommi Vatanen reports a relationship with Nestle Nutrition Institute (NNI) that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years) of 8,667 children showed high retention and compliance. End points of the presence of autoantibodies against insulin, GAD65, IA-2 and ZnT8 revealed the HLA-associated early appearance of insulin autoantibodies (1-3 years of age) and the later appearance of GAD65 autoantibodies. Competing autoantibodies against tissue transglutaminase (marking coeliac disease autoimmunity) also appeared early (2-4 years). Genetic and environmental factors, including enterovirus infection and gastroenteritis, support mechanistic differences underlying one phenotype of autoimmunity against insulin and another against GAD65. Infant growth and both probiotics and high protein intake affect the two phenotypes differently, as do serious life events during pregnancy. As the end of the TEDDY sampling phase is approaching, major omics approaches are in progress to further dissect the mechanisms that might explain the two possible endotypes of T1DM., (© 2024. Springer Nature Limited.)

Importance: A meta-analysis published in 2001 suggested that exposure to infections measured by day care attendance may be important in the pathogenesis of type 1 diabetes. Several new studies on the topic have since been published., Objective: To investigate the association between day care attendance and risk of type 1 diabetes and to include all available literature up to March 10, 2024., Data Sources: Data from PubMed and Web of Science were used and supplemented by bibliographies of the retrieved articles and searched for studies assessing the association between day care attendance and risk of type 1 diabetes., Study Selection: Studies that reported a measure of association between day care attendance and risk of type 1 diabetes were included., Data Extraction and Synthesis: Details, including exposure and outcome assessment and adjustment for confounders, were extracted from the included studies. The multivariable association with the highest number of covariates, lowest number of covariates, and unadjusted estimates and corresponding 95% CIs were extracted. DerSimonian and Laird random-effects meta-analyses were performed and yielded conservative confidence intervals around relative risks., Main Outcomes and Measures: The principal association measure was day care attendance vs no day care attendance and risk of type 1 diabetes., Results: Seventeen articles including 22 observational studies of 100 575 participants were included in the meta-analysis. Among the participants, 3693 had type 1 diabetes and 96 882 were controls. An inverse association between day care attendance and risk of type 1 diabetes was found (combined odds ratio, 0.68; 95% CI, 0.58-0.79; P < .001; adjusted for all available confounders). When the 3 cohort studies included were analyzed separately, the risk of type 1 diabetes was 15% lower in the group attending day care; however, the difference was not statistically significant (odds ratio, 0.85; 95% CI, 0.59-1.12; P = .37)., Conclusions and Relevance: These results demonstrated that day care attendance appears to be associated with a reduced risk of type 1 diabetes. Increased contacts with microbes in children attending day care compared with children who do not attend day care may explain these findings. However, further prospective cohort studies are needed to confirm the proposed association.