Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report

Research output: Contribution to journalArticle

Standard

Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report. / TEDDY Study Group; Krischer, Jeffrey P; Liu, Xiang; Vehik, Kendra; Akolkar, Beena; Hagopian, William A; Rewers, Marian J; She, Jin-Xiong; Toppari, Jorma; Ziegler, Anette-G; Lernmark, Åke; Agardh, Daniel (Contributor); Andrén Aronsson, Carin (Contributor); Ask, Maria (Contributor); Bremer, Jenny (Contributor); Ericson-Hallström, Emelie (Contributor); Björne Fors, Annika (Contributor); Fransson, Lina (Contributor); Gard, Thomas (Contributor); Bennet, Rasmus (Contributor); Hyberg, Susanne (Contributor); Jisser, Hanna (Contributor); Johansen, Fredrik (Contributor); Jónsdóttir, Berglind (Contributor); JOVIC, SILVIJA (Contributor); Elding Larsson, Helena (Contributor); Lindström, Marielle (Contributor); Lundgren, Markus (Contributor); Månsson Martinez, Maria (Contributor); Markan, Maria (Contributor); Melin, Marie Jessica (Contributor); Mestan, Zeliha (Contributor); Nilsson, Caroline N (Contributor); Ottosson, Karin (Contributor); Rahmati, Kobra (Contributor); Ramelius, Anita (Contributor); Salami, Falastin (Contributor); Sjöberg, Anette (Contributor); Sjöberg, Birgitta (Contributor); Törn, Carina (Contributor); Wallin, Anne (Contributor); Wimar, Åsa (Contributor); Åberg, Sofie (Contributor).

In: Diabetes Care, Vol. 42, No. 6, 06.2019, p. 1051-1060.

Research output: Contribution to journalArticle

Harvard

TEDDY Study Group, Krischer, JP, Liu, X, Vehik, K, Akolkar, B, Hagopian, WA, Rewers, MJ, She, J-X, Toppari, J, Ziegler, A-G, Lernmark, Å, Agardh, D, Andrén Aronsson, C, Ask, M, Bremer, J, Ericson-Hallström, E, Björne Fors, A, Fransson, L, Gard, T, Bennet, R, Hyberg, S, Jisser, H, Johansen, F, Jónsdóttir, B, JOVIC, SILVIJA, Elding Larsson, H, Lindström, M, Lundgren, M, Månsson Martinez, M, Markan, M, Melin, MJ, Mestan, Z, Nilsson, CN, Ottosson, K, Rahmati, K, Ramelius, A, Salami, F, Sjöberg, A, Sjöberg, B, Törn, C, Wallin, A, Wimar, Å & Åberg, S 2019, 'Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report', Diabetes Care, vol. 42, no. 6, pp. 1051-1060. https://doi.org/10.2337/dc18-2282

APA

TEDDY Study Group, Krischer, J. P., Liu, X., Vehik, K., Akolkar, B., Hagopian, W. A., ... Åberg, S. (2019). Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report. Diabetes Care, 42(6), 1051-1060. https://doi.org/10.2337/dc18-2282

CBE

TEDDY Study Group, Krischer JP, Liu X, Vehik K, Akolkar B, Hagopian WA, Rewers MJ, She J-X, Toppari J, Ziegler A-G, Lernmark Å, Agardh D, Andrén Aronsson C, Ask M, Bremer J, Ericson-Hallström E, Björne Fors A, Fransson L, Gard T, Bennet R, Hyberg S, Jisser H, Johansen F, Jónsdóttir B, JOVIC SILVIJA, Elding Larsson H, Lindström M, Lundgren M, Månsson Martinez M, Markan M, Melin MJ, Mestan Z, Nilsson CN, Ottosson K, Rahmati K, Ramelius A, Salami F, Sjöberg A, Sjöberg B, Törn C, Wallin A, Wimar Å, Åberg S. 2019. Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report. Diabetes Care. 42(6):1051-1060. https://doi.org/10.2337/dc18-2282

MLA

Vancouver

TEDDY Study Group, Krischer JP, Liu X, Vehik K, Akolkar B, Hagopian WA et al. Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report. Diabetes Care. 2019 Jun;42(6):1051-1060. https://doi.org/10.2337/dc18-2282

Author

TEDDY Study Group ; Krischer, Jeffrey P ; Liu, Xiang ; Vehik, Kendra ; Akolkar, Beena ; Hagopian, William A ; Rewers, Marian J ; She, Jin-Xiong ; Toppari, Jorma ; Ziegler, Anette-G ; Lernmark, Åke ; Agardh, Daniel ; Andrén Aronsson, Carin ; Ask, Maria ; Bremer, Jenny ; Ericson-Hallström, Emelie ; Björne Fors, Annika ; Fransson, Lina ; Gard, Thomas ; Bennet, Rasmus ; Hyberg, Susanne ; Jisser, Hanna ; Johansen, Fredrik ; Jónsdóttir, Berglind ; JOVIC, SILVIJA ; Elding Larsson, Helena ; Lindström, Marielle ; Lundgren, Markus ; Månsson Martinez, Maria ; Markan, Maria ; Melin, Marie Jessica ; Mestan, Zeliha ; Nilsson, Caroline N ; Ottosson, Karin ; Rahmati, Kobra ; Ramelius, Anita ; Salami, Falastin ; Sjöberg, Anette ; Sjöberg, Birgitta ; Törn, Carina ; Wallin, Anne ; Wimar, Åsa ; Åberg, Sofie. / Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report. In: Diabetes Care. 2019 ; Vol. 42, No. 6. pp. 1051-1060.

RIS

TY - JOUR

T1 - Predicting Islet Cell Autoimmunity and Type 1 Diabetes

T2 - Diabetes Reviews

AU - TEDDY Study Group

AU - Krischer, Jeffrey P

AU - Liu, Xiang

AU - Vehik, Kendra

AU - Akolkar, Beena

AU - Hagopian, William A

AU - Rewers, Marian J

AU - She, Jin-Xiong

AU - Toppari, Jorma

AU - Ziegler, Anette-G

AU - Lernmark, Åke

A2 - Agardh, Daniel

A2 - Andrén Aronsson, Carin

A2 - Ask, Maria

A2 - Bremer, Jenny

A2 - Ericson-Hallström, Emelie

A2 - Björne Fors, Annika

A2 - Fransson, Lina

A2 - Gard, Thomas

A2 - Bennet, Rasmus

A2 - Hyberg, Susanne

A2 - Jisser, Hanna

A2 - Johansen, Fredrik

A2 - Jónsdóttir, Berglind

A2 - JOVIC, SILVIJA

A2 - Elding Larsson, Helena

A2 - Lindström, Marielle

A2 - Lundgren, Markus

A2 - Månsson Martinez, Maria

A2 - Markan, Maria

A2 - Melin, Marie Jessica

A2 - Mestan, Zeliha

A2 - Nilsson, Caroline N

A2 - Ottosson, Karin

A2 - Rahmati, Kobra

A2 - Ramelius, Anita

A2 - Salami, Falastin

A2 - Sjöberg, Anette

A2 - Sjöberg, Birgitta

A2 - Törn, Carina

A2 - Wallin, Anne

A2 - Wimar, Åsa

A2 - Åberg, Sofie

N1 - © 2019 by the American Diabetes Association.

PY - 2019/6

Y1 - 2019/6

N2 - OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.

AB - OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.

U2 - 10.2337/dc18-2282

DO - 10.2337/dc18-2282

M3 - Article

VL - 42

SP - 1051

EP - 1060

JO - Diabetes Reviews

JF - Diabetes Reviews

SN - 1935-5548

IS - 6

ER -