Dataset Information

Metabolite-related dietary patterns and the development of islet autoimmunity.

ABSTRACT: The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts.

SUBMITTER: Johnson RK

PROVIDER: S-EPMC6794249 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolite-related dietary patterns and the development of islet autoimmunity.

Johnson Randi K RK Vanderlinden Lauren L DeFelice Brian C BC Kechris Katerina K Uusitalo Ulla U Fiehn Oliver O Sontag Marci M Crume Tessa T Beyerlein Andreas A Lernmark Åke Å Toppari Jorma J Ziegler Anette-G AG She Jin-Xiong JX Hagopian William W Rewers Marian M Akolkar Beena B Krischer Jeffrey J Virtanen Suvi M SM Norris Jill M JM

Scientific reports 20191015 1

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positi ...[more]

PMID: 31616039

Similar Datasets

Project description:ImportanceDietary proteins, such as gluten, have been suggested as triggers of the disease process in type 1 diabetes (T1D).ObjectiveTo study the associations of cereal, gluten, and dietary fiber intake with the development of islet autoimmunity (IA) and T1D.Design, setting, and participantsThe prospective birth cohort Finnish Type 1 Diabetes Prediction and Prevention Study recruited children with genetic susceptibility to type 1 diabetes from September 1996 to September 2004 from 2 university hospitals in Finland and followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Altogether 6081 infants (78% of those invited) participated in the study. Dietary data were available for 5714 children (94.0%) and dietary and IA data were available for 5545 children (91.2%), of whom 3762 (68%) had data on islet autoantibodies up to age 6 years. Information on T1D was available for all children. Data were analyzed in 2018 and end point data were updated in 2015.ExposuresEach child's intake of cereals, gluten, and dietary fiber was calculated from repeated 3-day food records up to 6 years.Main outcomes and measuresIslet autoimmunity was defined as repeated positivity for islet cell antibodies and at least 1 biochemical autoantibody of 3 analyzed, or T1D. Data on the diagnosis of T1D were obtained from Finnish Pediatric Diabetes Register.ResultsOf 5545 children (2950 boys [53.2%]), 246 (4.4%) developed IA and of 5714 children (3033 boys [53.1%]), 90 (1.6%) developed T1D during the 6-year follow-up. Based on joint models, the intake of oats (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13), wheat (HR, 1.09; 95% CI, 1.03-1.15), rye (HR, 1.13; 95% CI, 1.03-1.23), gluten-containing cereals (HR, 1.07; 95% CI, 1.03-1.11), gluten without avenin from oats (HR, 2.23; 95% CI, 1.40-3.57), gluten with avenin (HR, 2.06; 95% CI, 1.45-2.92), and dietary fiber (HR, 1.41; 95% CI, 1.10-1.81) was associated with the risk of developing IA (HRs for 1 g/MJ increase in intake). The intake of oats (HR, 1.10; 95% CI, 1.00-1.21) and rye (HR, 1.20; 95% CI, 1.03-1.41) was associated with the risk of developing T1D. After multiple testing correction, the associations with IA remained statistically significant.Conclusions and relevanceA high intake of oats, gluten-containing cereals, gluten, and dietary fiber was associated with an increased risk of IA. Further studies are needed to confirm or rule out the findings and study potential mechanisms.

Project description:Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.Clinicaltrials.gov NCT00623610.

Project description:Aims/hypothesisWe 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.MethodsParticipants 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.ResultsIn 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/interpretationIn 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.Trial registrationClinicalTrials.gov NCT00179777.

Dataset Information

Metabolite-related dietary patterns and the development of islet autoimmunity.

Publications

Metabolite-related dietary patterns and the development of islet autoimmunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets