Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease

Helena Elding Larsson, Kendra Vehik, Patricia Gesualdo, Beena Akolkar, William Hagopian, Jeffery Krischer, Åke Lernmark, Marian Rewers, Olli Simell, Jin-Xiong She, Anette Ziegler, Michael J. Haller

Research output: Contribution to journalArticle

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Abstract

Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tolerance test (OGTT), and (iii) risk for early T1D is related to country, population, human leukocyte antigen (HLA)-genotypes and immunological markers. Methods: Autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3months of age in children with genetic risk. Symptoms and laboratory values at diagnosis were obtained and reviewed for ADA criteria. Results: The first 100 children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although young, 36% had no symptoms and ketoacidosis was rare (8%). An OGTT diagnosed 9/30 (30%) children above 3yr of age but only 4/70 (5.7%) below the age of 3yr. FDRs had higher cumulative incidence than children from the general population (p<0.0001). Appearance of all three autoantibodies at seroconversion was associated with the most rapid development of T1D (HR=4.52, p=0.014), followed by the combination of GADA and IAA (HR=2.82, p<0.0001). Conclusions: Close follow-up of children with genetic risk enables early detection of T1D. Risk factors for rapid development of diabetes in this young population were FDR status and initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalPediatric Diabetes
Volume15
Issue number2
DOIs
StatePublished - Jan 1 2014

Fingerprint

Type 1 Diabetes Mellitus
Glutamate Decarboxylase
Class 8 Receptor-Like Protein Tyrosine Phosphatases
Glucose Tolerance Test
Autoantibodies
Population
Ketosis
Environmental Exposure
HLA Antigens
Autoimmunity
Genotype
Insulin
Incidence

Keywords

  • Autoantibodies
  • Diagnosis
  • Follow-up studies
  • TEDDY study
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

Cite this

Elding Larsson, H., Vehik, K., Gesualdo, P., Akolkar, B., Hagopian, W., Krischer, J., ... Haller, M. J. (2014). Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. Pediatric Diabetes, 15(2), 118-126. https://doi.org/10.1111/pedi.12066

Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. / Elding Larsson, Helena; Vehik, Kendra; Gesualdo, Patricia; Akolkar, Beena; Hagopian, William; Krischer, Jeffery; Lernmark, Åke; Rewers, Marian; Simell, Olli; She, Jin-Xiong; Ziegler, Anette; Haller, Michael J.

In: Pediatric Diabetes, Vol. 15, No. 2, 01.01.2014, p. 118-126.

Research output: Contribution to journalArticle

Elding Larsson, H, Vehik, K, Gesualdo, P, Akolkar, B, Hagopian, W, Krischer, J, Lernmark, Å, Rewers, M, Simell, O, She, J-X, Ziegler, A & Haller, MJ 2014, 'Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease', Pediatric Diabetes, vol. 15, no. 2, pp. 118-126. https://doi.org/10.1111/pedi.12066
Elding Larsson H, Vehik K, Gesualdo P, Akolkar B, Hagopian W, Krischer J et al. Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. Pediatric Diabetes. 2014 Jan 1;15(2):118-126. https://doi.org/10.1111/pedi.12066
Elding Larsson, Helena ; Vehik, Kendra ; Gesualdo, Patricia ; Akolkar, Beena ; Hagopian, William ; Krischer, Jeffery ; Lernmark, Åke ; Rewers, Marian ; Simell, Olli ; She, Jin-Xiong ; Ziegler, Anette ; Haller, Michael J. / Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. In: Pediatric Diabetes. 2014 ; Vol. 15, No. 2. pp. 118-126.
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abstract = "Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tolerance test (OGTT), and (iii) risk for early T1D is related to country, population, human leukocyte antigen (HLA)-genotypes and immunological markers. Methods: Autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3months of age in children with genetic risk. Symptoms and laboratory values at diagnosis were obtained and reviewed for ADA criteria. Results: The first 100 children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although young, 36{\%} had no symptoms and ketoacidosis was rare (8{\%}). An OGTT diagnosed 9/30 (30{\%}) children above 3yr of age but only 4/70 (5.7{\%}) below the age of 3yr. FDRs had higher cumulative incidence than children from the general population (p<0.0001). Appearance of all three autoantibodies at seroconversion was associated with the most rapid development of T1D (HR=4.52, p=0.014), followed by the combination of GADA and IAA (HR=2.82, p<0.0001). Conclusions: Close follow-up of children with genetic risk enables early detection of T1D. Risk factors for rapid development of diabetes in this young population were FDR status and initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA.",
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AU - Elding Larsson, Helena

AU - Vehik, Kendra

AU - Gesualdo, Patricia

AU - Akolkar, Beena

AU - Hagopian, William

AU - Krischer, Jeffery

AU - Lernmark, Åke

AU - Rewers, Marian

AU - Simell, Olli

AU - She, Jin-Xiong

AU - Ziegler, Anette

AU - Haller, Michael J.

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N2 - Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tolerance test (OGTT), and (iii) risk for early T1D is related to country, population, human leukocyte antigen (HLA)-genotypes and immunological markers. Methods: Autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3months of age in children with genetic risk. Symptoms and laboratory values at diagnosis were obtained and reviewed for ADA criteria. Results: The first 100 children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although young, 36% had no symptoms and ketoacidosis was rare (8%). An OGTT diagnosed 9/30 (30%) children above 3yr of age but only 4/70 (5.7%) below the age of 3yr. FDRs had higher cumulative incidence than children from the general population (p<0.0001). Appearance of all three autoantibodies at seroconversion was associated with the most rapid development of T1D (HR=4.52, p=0.014), followed by the combination of GADA and IAA (HR=2.82, p<0.0001). Conclusions: Close follow-up of children with genetic risk enables early detection of T1D. Risk factors for rapid development of diabetes in this young population were FDR status and initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA.

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KW - Autoantibodies

KW - Diagnosis

KW - Follow-up studies

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KW - Type 1 diabetes

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