Pancreatic islet autoantibodies as predictors of type 1 diabetes in the diabetes prevention trial-type 1

Tihamer Orban, Jay M Sosenko, David Cuthbertson, Jeffrey P. Krischer, Jay S Skyler, Richard Jackson, Liping Yu, Jerry P. Palmer, Desmond Schatz, George Eisenbarth

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - There is limited information from large-scale prospective studies regarding the prediction of type 1 diabetes by specific types of pancreatic islet autoantibodies, either alone or in combination. Thus, we studied the extent to which specific autoantibodies are predictive of type 1 diabetes. RESEARCH DESIGN AND METHODS - Two cohorts were derived from the first screening for islet cell autoantibodies (ICAs) in the Diabetes Prevention Trial-Type 1 (DPT-1). Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4% ICA+). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3% ICA+). RESULTS- In both cohorts autoantibody number was highly predictive of type 1 diabetes (P < 0.001). The Questionnaire cohort was used to assess prediction according to the type of autoantibody. As single autoantibodies, ICA (3.9%), GAD65 (4.4%), and ICA512 (4.6%) were similarly predictive of type 1 diabetes in proportional hazards models (P < 0.001 for all). However, no subjects with mIAA as single autoantibodies developed type 1 diabetes. As second autoantibodies, all except mIAA added significantly (P < 0.001) to the prediction of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers were predictive of type 1 diabetes. CONCLUSIONS - The data indicate that the number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less predictive of type 1 diabetes than other autoantibodies. Autoantibody number, type of autoantibody, and autoantibody titer must be carefully considered in planning prevention trials for type 1 diabetes.

Original languageEnglish
Pages (from-to)2269-2274
Number of pages6
JournalDiabetes Care
Volume32
Issue number12
DOIs
StatePublished - Dec 1 2009

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Type 1 Diabetes Mellitus
Islets of Langerhans
Autoantibodies
Class 8 Receptor-Like Protein Tyrosine Phosphatases
Insulinoma
Proportional Hazards Models

ASJC Scopus subject areas

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

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Pancreatic islet autoantibodies as predictors of type 1 diabetes in the diabetes prevention trial-type 1. / Orban, Tihamer; Sosenko, Jay M; Cuthbertson, David; Krischer, Jeffrey P.; Skyler, Jay S; Jackson, Richard; Yu, Liping; Palmer, Jerry P.; Schatz, Desmond; Eisenbarth, George.

In: Diabetes Care, Vol. 32, No. 12, 01.12.2009, p. 2269-2274.

Research output: Contribution to journalArticle

Orban, T, Sosenko, JM, Cuthbertson, D, Krischer, JP, Skyler, JS, Jackson, R, Yu, L, Palmer, JP, Schatz, D & Eisenbarth, G 2009, 'Pancreatic islet autoantibodies as predictors of type 1 diabetes in the diabetes prevention trial-type 1', Diabetes Care, vol. 32, no. 12, pp. 2269-2274. https://doi.org/10.2337/dc09-0934
Orban, Tihamer ; Sosenko, Jay M ; Cuthbertson, David ; Krischer, Jeffrey P. ; Skyler, Jay S ; Jackson, Richard ; Yu, Liping ; Palmer, Jerry P. ; Schatz, Desmond ; Eisenbarth, George. / Pancreatic islet autoantibodies as predictors of type 1 diabetes in the diabetes prevention trial-type 1. In: Diabetes Care. 2009 ; Vol. 32, No. 12. pp. 2269-2274.
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abstract = "OBJECTIVE - There is limited information from large-scale prospective studies regarding the prediction of type 1 diabetes by specific types of pancreatic islet autoantibodies, either alone or in combination. Thus, we studied the extent to which specific autoantibodies are predictive of type 1 diabetes. RESEARCH DESIGN AND METHODS - Two cohorts were derived from the first screening for islet cell autoantibodies (ICAs) in the Diabetes Prevention Trial-Type 1 (DPT-1). Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4{\%} ICA+). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3{\%} ICA+). RESULTS- In both cohorts autoantibody number was highly predictive of type 1 diabetes (P < 0.001). The Questionnaire cohort was used to assess prediction according to the type of autoantibody. As single autoantibodies, ICA (3.9{\%}), GAD65 (4.4{\%}), and ICA512 (4.6{\%}) were similarly predictive of type 1 diabetes in proportional hazards models (P < 0.001 for all). However, no subjects with mIAA as single autoantibodies developed type 1 diabetes. As second autoantibodies, all except mIAA added significantly (P < 0.001) to the prediction of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers were predictive of type 1 diabetes. CONCLUSIONS - The data indicate that the number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less predictive of type 1 diabetes than other autoantibodies. Autoantibody number, type of autoantibody, and autoantibody titer must be carefully considered in planning prevention trials for type 1 diabetes.",
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AU - Skyler, Jay S

AU - Jackson, Richard

AU - Yu, Liping

AU - Palmer, Jerry P.

AU - Schatz, Desmond

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