The DIPP project: 20 years of discovery in type 1 diabetes

Haller, Michael J.; Schatz, Desmond

doi:10.1111/pedi.12398

Cited by 21 publications

(18 citation statements)

References 16 publications

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“…Study design and protocol In this study, the samples were obtained from the Finnish DIPP study [18]. The DIPP study has screened more than 230,000 newborn infants for HLAconferred susceptibility to type 1 diabetes in three university hospitals: those at Turku, Tampere and Oulu in Finland [19]. The children involved in the current study were chosen from the subset of DIPP children which were from the city of Tampere, Finland.…”

Section: Methodsmentioning

confidence: 99%

Metabolic alterations in immune cells associate with progression to type 1 diabetes

et al. 2020

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Aims/hypothesis Previous metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes. Methods In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to ≥1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10). Results During the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05107-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.* Partho Sen partho.sen@utu.fi * Mikael Knip

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Section: Methodsmentioning

confidence: 99%

Metabolic alterations in immune cells associate with progression to type 1 diabetes

et al. 2020

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“…The samples were anonymised and used in the development of antibody tests. Control serum samples included laboratory personnel and the participants of the Autoimmune defence and living environment-study (ADELE) [18] and negative control samples from 6-month old children who were participating in the Diabetes prediction and prevention-study (DIPP) [19]. All participants or their legal guardians gave informed consent.…”

Section: Human Samples Ethics Statementmentioning

confidence: 99%

Antibody Responses against Enterovirus Proteases are Potential Markers for an Acute Infection

Saarinen

Stone

Hankaniemi

et al. 2020

Viruses

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Background: Enteroviruses are a group of common non-enveloped RNA viruses that cause symptoms ranging from mild respiratory infections to paralysis. Due to the abundance of enterovirus infections it is hard to distinguish between on-going and previous infections using immunological assays unless the IgM fraction is studied. Methods: In this study we show using Indirect ELISA and capture IgM ELISA that an IgG antibody response against the nonstructural enteroviral proteins 2A and 3C can be used to distinguish between IgM positive (n = 22) and IgM negative (n = 20) human patients with 83% accuracy and a diagnostic odds ratio of 30. Using a mouse model, we establish that the antibody response to the proteases is short-lived compared to the antibody response to the structural proteins in. As such, the protease antibody response serves as a potential marker for an acute infection. Conclusions: Antibody responses against enterovirus proteases are shorter-lived than against structural proteins and can differentiate between IgM positive and negative patients, and therefore they are a potential marker for acute infections.

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“…The plasma samples were from the Finnish Type 1 Diabetes Prevention and Prediction Study (DIPP) 35 . The DIPP study has screened more than 220,000 newborn infants for HLA-conferred susceptibility to T1D in three university hospitals (Turku, Tampere, and Oulu) in Finland 36 . The subjects in the current study were from the subset of DIPP children from the Tampere study centre.…”

Section: Methodsmentioning

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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The DIPP project: 20 years of discovery in type 1 diabetes

Cited by 21 publications

References 16 publications

Metabolic alterations in immune cells associate with progression to type 1 diabetes

Metabolic alterations in immune cells associate with progression to type 1 diabetes

Antibody Responses against Enterovirus Proteases are Potential Markers for an Acute Infection

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

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