Reversion of β-cell autoimmunity changes risk of type 1 diabetes: TEDDY study

Kendra Vehik, Kristian F. Lynch, Desmond A. Schatz, Beena Akolkar, William Hagopian, Marian Rewers, Jin-Xiong She, Olli Simell, Jorma Toppari, Anette G. Ziegle, Ake Lernmark, Ezio Bonifacio, Jeffrey P. Krischer

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Abstract

OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (<1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.

Original languageEnglish (US)
Pages (from-to)1535-1542
Number of pages8
JournalDiabetes Care
Volume39
Issue number9
DOIs
StatePublished - Sep 1 2016

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Autoimmunity
Type 1 Diabetes Mellitus
Autoantibodies
Insulin
Insulinoma
Antibodies

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Vehik, K., Lynch, K. F., Schatz, D. A., Akolkar, B., Hagopian, W., Rewers, M., ... Krischer, J. P. (2016). Reversion of β-cell autoimmunity changes risk of type 1 diabetes: TEDDY study. Diabetes Care, 39(9), 1535-1542. https://doi.org/10.2337/dc16-0181

Reversion of β-cell autoimmunity changes risk of type 1 diabetes : TEDDY study. / Vehik, Kendra; Lynch, Kristian F.; Schatz, Desmond A.; Akolkar, Beena; Hagopian, William; Rewers, Marian; She, Jin-Xiong; Simell, Olli; Toppari, Jorma; Ziegle, Anette G.; Lernmark, Ake; Bonifacio, Ezio; Krischer, Jeffrey P.

In: Diabetes Care, Vol. 39, No. 9, 01.09.2016, p. 1535-1542.

Research output: Contribution to journalArticle

Vehik, K, Lynch, KF, Schatz, DA, Akolkar, B, Hagopian, W, Rewers, M, She, J-X, Simell, O, Toppari, J, Ziegle, AG, Lernmark, A, Bonifacio, E & Krischer, JP 2016, 'Reversion of β-cell autoimmunity changes risk of type 1 diabetes: TEDDY study', Diabetes Care, vol. 39, no. 9, pp. 1535-1542. https://doi.org/10.2337/dc16-0181
Vehik K, Lynch KF, Schatz DA, Akolkar B, Hagopian W, Rewers M et al. Reversion of β-cell autoimmunity changes risk of type 1 diabetes: TEDDY study. Diabetes Care. 2016 Sep 1;39(9):1535-1542. https://doi.org/10.2337/dc16-0181
Vehik, Kendra ; Lynch, Kristian F. ; Schatz, Desmond A. ; Akolkar, Beena ; Hagopian, William ; Rewers, Marian ; She, Jin-Xiong ; Simell, Olli ; Toppari, Jorma ; Ziegle, Anette G. ; Lernmark, Ake ; Bonifacio, Ezio ; Krischer, Jeffrey P. / Reversion of β-cell autoimmunity changes risk of type 1 diabetes : TEDDY study. In: Diabetes Care. 2016 ; Vol. 39, No. 9. pp. 1535-1542.
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abstract = "OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19{\%}) and insulin (29{\%}), but was largely restricted to children who had single autoantibodies (24{\%}) and rare in children who had developed multiple autoantibodies (<1{\%}). Most (85{\%}) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.",
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T1 - Reversion of β-cell autoimmunity changes risk of type 1 diabetes

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AU - Vehik, Kendra

AU - Lynch, Kristian F.

AU - Schatz, Desmond A.

AU - Akolkar, Beena

AU - Hagopian, William

AU - Rewers, Marian

AU - She, Jin-Xiong

AU - Simell, Olli

AU - Toppari, Jorma

AU - Ziegle, Anette G.

AU - Lernmark, Ake

AU - Bonifacio, Ezio

AU - Krischer, Jeffrey P.

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N2 - OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (<1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.

AB - OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (<1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.

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