The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients

Jay M Sosenko, Jay S Skyler, Jerry P. Palmer, Jeffrey P. Krischer, Liping Yu, Jeffrey Mahon, Craig A. Beam, David C. Boulware, Lisa Rafkin, Desmond Schatz, George Eisenbarth

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE-We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS-TrialNet Natural History Study participants (n = 784)were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. RESULTS-The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23- 3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded fromthe risk scoremodel. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1Dmore accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). CONCLUSIONS-These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels ofmultiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

Original languageEnglish
Pages (from-to)2615-2620
Number of pages6
JournalDiabetes Care
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2013

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Type 1 Diabetes Mellitus
Autoantibodies
Natural History
Proportional Hazards Models
ROC Curve
Research Design

ASJC Scopus subject areas

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

Cite this

The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. / Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P.; Krischer, Jeffrey P.; Yu, Liping; Mahon, Jeffrey; Beam, Craig A.; Boulware, David C.; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George.

In: Diabetes Care, Vol. 36, No. 9, 01.09.2013, p. 2615-2620.

Research output: Contribution to journalArticle

Sosenko, Jay M ; Skyler, Jay S ; Palmer, Jerry P. ; Krischer, Jeffrey P. ; Yu, Liping ; Mahon, Jeffrey ; Beam, Craig A. ; Boulware, David C. ; Rafkin, Lisa ; Schatz, Desmond ; Eisenbarth, George. / The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. In: Diabetes Care. 2013 ; Vol. 36, No. 9. pp. 2615-2620.
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abstract = "OBJECTIVE-We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS-TrialNet Natural History Study participants (n = 784)were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. RESULTS-The ABRS was strongly predictive of T1D (hazard ratio [with 95{\%} CI] 2.72 [2.23- 3.31], P < 0.001). Receiver operating characteristic curve areas (with 95{\%} CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded fromthe risk scoremodel. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1Dmore accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). CONCLUSIONS-These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels ofmultiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.",
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T1 - The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients

AU - Sosenko, Jay M

AU - Skyler, Jay S

AU - Palmer, Jerry P.

AU - Krischer, Jeffrey P.

AU - Yu, Liping

AU - Mahon, Jeffrey

AU - Beam, Craig A.

AU - Boulware, David C.

AU - Rafkin, Lisa

AU - Schatz, Desmond

AU - Eisenbarth, George

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AB - OBJECTIVE-We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS-TrialNet Natural History Study participants (n = 784)were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. RESULTS-The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23- 3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded fromthe risk scoremodel. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1Dmore accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). CONCLUSIONS-These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels ofmultiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

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