Update from the TEDDY Study

Marian Rewers, MD, PhD; Qian Li, PhD; Kendra Vehik, PhD, MPH; William Hagopian, MD, PhD

ADA 2020 - Oral session

5 minute listen
9 minute read

Key messages

  • Further analysis of the TEDDY population has identified a risk score for type 1 diabetes as well as distinct metabolic clusters that may have clinical relevance.
  • Change in HbA1c was a good diagnostic tool for type 1 diabetes.
  • There is a greater than expected overlap between type 1 diabetes and celiac disease.

Key messages

  • Further analysis of the TEDDY population has identified a risk score for type 1 diabetes as well as distinct metabolic clusters that may have clinical relevance.
  • Change in HbA1c was a good diagnostic tool for type 1 diabetes.
  • There is a greater than expected overlap between type 1 diabetes and celiac disease.

Background

What do we already know about this topic?

  • Celiac disease, an autoimmune condition, shares many genetic factors with type 1 diabetes (T1D).
  • The TEDDY (The Environmental Determinants of Diabetes in the Young) study is defining the environmental determinants and natural history of islet autoimmunity and T1D.
  • More than 400,000 newborns were screened in hospitals affiliated with the study centers between September 2004 and February 2010.

The update

Determinants of islet autoimmunity and clinical implications

  • More than 7000 newborns carrying HLA antigen genotypes associated with T1D were enrolled.
  • A risk score using autoantibodies, and genetic and clinical markers was found that can aid in predicting the risk of T1D over horizons of up to 8 years.
  • Autoimmune phenotypes point to distinct etiologic endotypes.
  • Early ‘IAA-first’ phenotype and later a ‘GADA-first’ phenotype may mark distinct triggers of islet autoimmunity.
  • Prolonged shedding of enteroviruses predicts development of islet autoimmunity across all TEDDY centers and may be associated with ‘IAA-first’.
  • Subtle associations between microbiome taxonomy/function and islet autoimmunity exist, and may also be involved with diet-microbiome interactions.
  • Furthermore, gene-micronutrient interactions may influence the risk.

Metabolome signals in the TEDDY study

  • Metabolics data profiling was carried out using samples obtained in the TEDDY study.
  • Four clusters were identified in the children’s lipidome.
  • Autoantibody clusters were also found that showed stratified seroconversion to T1D.
  • Erythrocyte omega-3 fatty acids showed a positive interaction with cholesterol esters, but negative correlation with ascorbic acid and 25(OH) vitamin D.
  • Ascorbic acid and 25(OH) vitamin D may have a protective effect on T1D progression following seroconversion.

HbA1c - Is it a good diagnostic predictor of type 1 onset in a pediatric population?

  • Risk factors associated with a change in HbA1c was examined, and identified number of antibodies at HbA1c change, age at baseline, and HbA1c at baseline.
  • The change in HbA1c was found to predict T1D in children.
  • A rapid change in HbA1c did not predict T1D.
  • Change in HbA1c was a good diagnostic measure in the young population, and was as reliable as a single oral glucose tolerance test for T1D.

Dissecting the type 1 diabetes and celiac disease overlap in the TEDDY study

  • Extensive overlap was found between celiac autoimmunity (TGA, transglutaminase autoantibodies) and T1D in the TEDDY cohort.
  • Islet autoimmunity usually preceded TGA, and islet autoimmunity increased the risk of subsequent TGA.
  • While gluten intake was a strong risk factor for TGA, neither intake nor age at gluten introduction were consistent risk factors for both types of autoimmunity.
  • Enteroviral infection was associated with both islet autoimmunity and TGA, the latter when stratified by gluten intake, and may explain some of the overlap.

Conclusions

  • A risk score for T1D was identified using autoantibodies, and genetic and clinical markers.
  • Distinct metabolic clusters were identified in the TEDDY population.
  • Change in HbA1c was a good diagnostic tool for T1D.
  • The observed overlap between T1D and celiac disease was greater than expected.

Conclusions

  • A risk score for T1D was identified using autoantibodies, and genetic and clinical markers.
  • Distinct metabolic clusters were identified in the TEDDY population.
  • Change in HbA1c was a good diagnostic tool for T1D.
  • The observed overlap between T1D and celiac disease was greater than expected.

This is a highlights summary of an oral session given at the ADA 2020 - 80th Scientific Sessions and presented by:

Marian Rewers, MD, PhD
Dept. of Pediatrics, The Barbara Davis Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

Qian Li, PhD
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

Kendra Vehik, PhD, MPH
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

William Hagopian, MD, PhD
Pacific Northwest Research Institute, Seattle, WA, USA

The content is produced by Infomedica, the official reporting partner of ADA 2020 Virtual Meeting. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Dana M. Dabelea, MD, PhD, the scientific editor of the program.

The presenting authors of the original session had no part in the creation of this conference highlights summary.

In addition, an expert commentary on the topic has been provided by:

Prof. Tatjana Milenkovic, MD
Clinic of Endocrinology, Diabetes and Metabolic Disorders,
University “St Cyril and Methodius”, Skopje, Macedonia
President of the Macedonian Scientific Society of Endocrinologists and Diabetologists
Prof. Tatjana Milenkovic, MD
Clinic of Endocrinology, Diabetes and Metabolic Disorders,
University “St Cyril and Methodius”, Skopje, Macedonia
President of the Macedonian Scientific Society of Endocrinologists and Diabetologists
 

Prof. Tatjana Milenkovic is a professor of internal medicine at the University “St Cyril and Methodius”, Medical Faculty in Skopje, Macedonia. She works at the Clinic of Endocrinology, Diabetes and Metabolic Diseases since 1985, where in 1995 she has established the Department of education of people with diabetes – and she has been Head of the department ever since. She is a member of the Executive Committee of Diabetes Education Study group (DESG). She is the President of Macedonian Diabetes Association, since 2013, the President of the Macedonian Scientific Association of endocrinologists and diabetologists since 2014 and member of IDF Europe board for biennium 2020-2021.



Diabetes
Epidemiology/Genetics


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