A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history

Jay M. Sosenko, Jay S. Skyler, Linda DiMeglio, Craig A. Beam, Jeffrey P. Krischer, Carla J. Greenbaum, David Boulware, Lisa E. Rafkin, Della Matheson, Kevan C. Herold, Jeffrey Mahon, Jerry P. Palmer

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals. RESEARCH DESIGN AND METHODS: Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participantswere studied. Ametabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only)were comparedwith Index60 <2.00 and 2-h glucose ≥200mg/dL (2hglu+Only)OGTTs as criteria for T1D. Individualswere assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis. RESULTS: Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range222 to234%in DPT-1 and 214 to 227%in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs. CONCLUSIONS: An approach based on prediction and natural history appears to have utility for diagnosing T1D.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalDiabetes Care
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2015

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Glucose Tolerance Test
Natural History
Type 1 Diabetes Mellitus
Autoantibodies
C-Peptide
Glucose
ROC Curve
Fasting
Research Design

ASJC Scopus subject areas

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

Cite this

Sosenko, J. M., Skyler, J. S., DiMeglio, L., Beam, C. A., Krischer, J. P., Greenbaum, C. J., ... Palmer, J. P. (2015). A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history. Diabetes Care, 38(2), 271-276. https://doi.org/10.2337/dc14-1813

A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history. / Sosenko, Jay M.; Skyler, Jay S.; DiMeglio, Linda; Beam, Craig A.; Krischer, Jeffrey P.; Greenbaum, Carla J.; Boulware, David; Rafkin, Lisa E.; Matheson, Della; Herold, Kevan C.; Mahon, Jeffrey; Palmer, Jerry P.

In: Diabetes Care, Vol. 38, No. 2, 01.02.2015, p. 271-276.

Research output: Contribution to journalArticle

Sosenko, JM, Skyler, JS, DiMeglio, L, Beam, CA, Krischer, JP, Greenbaum, CJ, Boulware, D, Rafkin, LE, Matheson, D, Herold, KC, Mahon, J & Palmer, JP 2015, 'A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history', Diabetes Care, vol. 38, no. 2, pp. 271-276. https://doi.org/10.2337/dc14-1813
Sosenko, Jay M. ; Skyler, Jay S. ; DiMeglio, Linda ; Beam, Craig A. ; Krischer, Jeffrey P. ; Greenbaum, Carla J. ; Boulware, David ; Rafkin, Lisa E. ; Matheson, Della ; Herold, Kevan C. ; Mahon, Jeffrey ; Palmer, Jerry P. / A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history. In: Diabetes Care. 2015 ; Vol. 38, No. 2. pp. 271-276.
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AU - Skyler, Jay S.

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AU - Beam, Craig A.

AU - Krischer, Jeffrey P.

AU - Greenbaum, Carla J.

AU - Boulware, David

AU - Rafkin, Lisa E.

AU - Matheson, Della

AU - Herold, Kevan C.

AU - Mahon, Jeffrey

AU - Palmer, Jerry P.

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N2 - OBJECTIVE: We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals. RESEARCH DESIGN AND METHODS: Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participantswere studied. Ametabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only)were comparedwith Index60 <2.00 and 2-h glucose ≥200mg/dL (2hglu+Only)OGTTs as criteria for T1D. Individualswere assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis. RESULTS: Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range222 to234%in DPT-1 and 214 to 227%in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs. CONCLUSIONS: An approach based on prediction and natural history appears to have utility for diagnosing T1D.

AB - OBJECTIVE: We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals. RESEARCH DESIGN AND METHODS: Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participantswere studied. Ametabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only)were comparedwith Index60 <2.00 and 2-h glucose ≥200mg/dL (2hglu+Only)OGTTs as criteria for T1D. Individualswere assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis. RESULTS: Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range222 to234%in DPT-1 and 214 to 227%in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs. CONCLUSIONS: An approach based on prediction and natural history appears to have utility for diagnosing T1D.

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