Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study

Jørgenrud, Benedicte; Stene, Lars C.; Tapia, German; Bøås, Håkon; Pepaj, Milaim; Berg, Jens Petter; Thorsby, Per Medbøe; Orešič, Matej; Hyötyläinen, Tuulia; Rønningen, Kjersti S.

doi:10.1111/pedi.12360

Cited by 13 publications

(11 citation statements)

References 23 publications

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“…While most of the amino acids were downregulated in PT1D as compared to CTR and P1Ab, methionine remained persistently upregulated in T1D progressors. This appears to be in disagreement with previous studies in BABYDIAB and MIDIA cohorts, which showed decreased level of methionine in autoantibody positive individuals and T1D progressors, respectively 18, 30 . This discrepancy may however be explained: (1) BABYDIAB study compared children seroconverting early in life (≤2 years) to those who developed autoantibodies at older age, while (2) MIDIA study highlighted differences, which were mainly linked to the age of the children and the duration of breastfeeding 30 .…”

Section: Discussioncontrasting

confidence: 99%

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Lamichhane

Kemppainen

Trošt

et al. 2018

Preprint

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33Previous studies suggest that metabolic dysregulation precedes the onset of type 1 diabetes 34 (T1D). However, these metabolic disturbances and their specific role in disease initiation remain 35 poorly understood. Here we analysed polar metabolites from 415 longitudinal plasma samples in a 36 prospective cohort of children in three study groups: those who progressed to T1D (PT1D), who 37 seroconverted to one islet autoantibody (Ab) but not to T1D (P1Ab), and Ab-negative controls 38 (CTR). In early infancy, PT1D associated with downregulated amino acids, sugar derivatives and 39 fatty acids, including catabolites of microbial origin, as compared to CTR. Methionine remained 40 persistently upregulated in PT1D as compared to CTR and P1Ab. Appearance of islet 41 autoantibodies associated with decreased glutamic and aspartic acids. Our findings suggest that 42 children who progress to T1D have a unique metabolic profile, which is however altered with the 43 onset of islet autoantibodies. Our findings may assist in early prediction of T1D. 44 45 46

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Section: Discussioncontrasting

confidence: 99%

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Lamichhane

Kemppainen

Trošt

et al. 2018

Preprint

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“…While most of the amino acids were downregulated in the PT1D group compared with the CTRL and P1Ab groups, methionine remained persistently upregulated in type 1 diabetes progressors. This appears to be in disagreement with previous studies in BABYDIAB and Environmental Triggers for Type 1 Diabetes (MIDIA) cohorts, which showed a decreased level of methionine in autoantibody-positive individuals and type 1 diabetes progressors, respectively [29, 41]. This discrepancy may, however, be explained: [1] the BABYDIAB study compared children seroconverting early in life (≤2 years) with those who developed autoantibodies at an older age; while [2] the MIDIA study highlighted differences that were mainly linked to the age of the children and the duration of breastfeeding [41].…”

Section: Discussioncontrasting

confidence: 95%

Circulating metabolites in progression to islet autoimmunity and type 1 diabetes

et al. 2019

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Aims/hypothesisMetabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.MethodsWe analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.ResultsIn early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.Conclusions/interpretationOur findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-04980-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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“…Other dicarboxylic acids associated with increased mAb+ risk included the tricarboxylic acid (TCA) cycle intermediaries succinic acid and malic acid. While metabolomics studies in Norway and Germany did not identify TCA cycle metabolites 5,6 , a previous study in Finnish children found both succinic acid and glutamic acid were increased in type 1 diabetes cases 0–9 months prior to autoantibody appearance 10 . We were not able to examine glutamic acid as its measurement was inhibited by the use of citrate tubes for plasma collection and storage in TEDDY.…”

Section: Discussionmentioning

confidence: 88%

“…Metabolomics differences between IA cases and controls mostly have been found at the time of seroconversion, but are inconsistent across studies conducted in country-specific populations 4–7 . Previous country-specific studies used different laboratories to measure varying types (primary/polar 5 , lipids 4,7–9 , both 6,10 ) and amounts of metabolomics features (from 106 7 to 540 6 ), and conducted studies at varying ages and stages of the disease course (cord blood 4,7,8 , at seroconversion to IA 6 , longitudinally 5,9,10 ). Given these methodological differences, it is unclear whether differences in study findings are due to technical artefacts, or whether they represent truly different associations by geography or other meaningful characteristic.…”

Section: Introductionmentioning

confidence: 99%

Metabolite-related dietary patterns and the development of islet autoimmunity

Johnson

Vanderlinden

DeFelice

et al. 2019

Sci Rep

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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.

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Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study

Abstract: Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.

Cited by 13 publications

References 23 publications

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Circulating metabolites in progression to islet autoimmunity and type 1 diabetes

Metabolite-related dietary patterns and the development of islet autoimmunity

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