Oral Glucose Tolerance Test Measures of First-phase Insulin Response and Their Predictive Ability for Type 1 Diabetes

David A. Baidal, Megan Warnock, Ping Xu, Susan Geyer, Jennifer B. Marks, Antoinette Moran, Jay Sosenko, Carmella Evans-Molina

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Abstract

CONTEXT: Decreased first-phase insulin response (FPIR) during intravenous glucose tolerance testing (IVGTT) is an early indicator of β-cell dysfunction and predictor of type 1 diabetes (T1D).

OBJECTIVE: Assess whether oral glucose tolerance test (OGTT) measures could serve as FPIR alternatives in their ability to predict T1D in autoantibody positive (Aab+) subjects.

DESIGN: OGTT and IVGTT were performed within 30 days of each other. Eleven OGTT variables were evaluated for (1) correlation with FPIR and (2) T1D prediction.

SETTING: Type 1 Diabetes TrialNet "Oral Insulin for Prevention of Diabetes in Relatives at Risk for T1D" (TN-07) and Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) studies clinical sites.

PATIENTS: TN-07 (n = 292; age 9.4 ± 6.1 years) and DPT-1 (n = 194; age 15.1 ± 10.0 years) Aab + relatives of T1D individuals.

MAIN OUTCOME MEASURES: (1) Correlation coefficients of OGTT measures with FPIR and (2) T1D prediction at 2 years using area under receiver operating characteristic (ROCAUC) curves.

RESULTS: Index60 showed the strongest correlation in DPT-1 (r = -0.562) but was weaker in TN-07 (r = -0.378). C-peptide index consistently showed good correlation with FPIR across studies (TN-07, r = 0.583; DPT-1, r = 0.544; P < 0.0001). Index60 and C-peptide index had the highest ROCAUCs for T1D prediction (0.778 vs 0.717 in TN-07 and 0.763 vs 0.721 in DPT-1, respectively; P = NS), followed by FPIR (0.707 in TN-07; 0.628 in DPT-1).

CONCLUSIONS: C-peptide index was the strongest measure to correlate with FPIR in both studies. Index60 and C-peptide index had the highest predictive accuracy for T1D and were comparable. OGTTs could be considered instead of IVGTTs for subject stratification in T1D prevention trials.

Original languageEnglish (US)
Pages (from-to)E3273-E3280
JournalJournal of Clinical Endocrinology and Metabolism
Volume107
Issue number8
DOIs
StatePublished - Aug 1 2022

Bibliographical note

Funding Information:
This work was funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK085476, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4 DK117009-01, and the Juvenile Diabetes Research Foundation. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF.

Publisher Copyright:
© 2022 Endocrine Society. All rights reserved.

Keywords

  • C-peptide index
  • Index60
  • TrialNet
  • first-phase insulin response
  • oral glucose tolerance test
  • type 1 diabetes
  • Glucose Tolerance Test
  • Autoantibodies
  • Humans
  • Child, Preschool
  • Blood Glucose
  • Clinical Trials as Topic
  • C-Peptide
  • Insulin
  • Young Adult
  • Adolescent
  • Diabetes Mellitus, Type 1/diagnosis
  • Adult
  • Child

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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