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Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls.

ABSTRACT: OBJECTIVE:To explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community. METHODS:TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3?months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both participated in long-term follow up after diagnosis. Hemoglobin A1c (HbA1c) and mixed meal tolerance test were performed within 1?month of diabetes onset, then at 3, 6, and 12?months, and biannually thereafter. RESULTS:Comparison of 43 TEDDY and 43 paired control children showed that TEDDY children often had no symptoms (58%) at diagnosis and none had diabetic ketoacidosis (DKA) compared with 98% with diabetes symptoms and 14% DKA in the controls (P?

SUBMITTER: Steck AK

PROVIDER: S-EPMC5529265 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls.

Steck Andrea K AK Larsson Helena Elding HE Liu Xiang X Veijola Riitta R Toppari Jorma J Hagopian William A WA Haller Michael J MJ Ahmed Simi S Akolkar Beena B Lernmark Åke Å Rewers Marian J MJ Krischer Jeffrey P JP

Pediatric diabetes 20170127 8

<h4>Objective</h4>To explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community.<h4>Methods</h4>TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3 months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both pa ...[more]

PMID: 28127835

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Project description:Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) from age-matched T1D and control children using flow cytometry. We observed that CD8 and DN MAIT cell frequencies were similarly abundant between the two groups. We tested for associations between MAIT cell frequency and T1D-associated parameters, which could reveal a pathogenic role for MAIT cells in the absence of changes in frequency. We found no significant associations between CD8 and DN MAIT cell frequency and levels of islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65) autoantibodies, zinc transporter 8 (ZNT8) autoantibodies, and insulinoma antigen 2 (IA-2) autoantibodies. Furthermore, CD8 and DN MAIT cell frequencies were not significantly associated with time since diagnosis, c-peptide levels, HbA1c, and BMI. As we have examined this cohort for multiple soluble factors previously, we tested for associations between relevant factors and MAIT cell frequency. These could help to explain the broad range of MAIT frequencies we observed and/or indicate disease-associated processes. Although we found nothing disease-specific, we observed that levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were all associated with MAIT cell frequency. Finally, previous cytomegalovirus infection was associated with reduced CD8 and DN MAIT cells. From this evaluation, we found no connections between CD8 and DN MAIT cells and children with T1D. However, we did observe several intrinsic and extrinsic factors that could influence peripheral MAIT cell abundance among all children. These factors may be worth consideration in future experimental design.

Project description:ObjectiveIncreased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.Research design and methodsA joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.ResultsIt was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001).ConclusionIn conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.

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Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls.

Publications

Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls.

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