Dysglycemia and Index60 as prediagnostic end points for type 1 diabetes prevention trials

Brandon M. Nathan, David Boulware, Susan Geyer, Mark A. Atkinson, Peter Colman, Robin Goland, William Russell, John M. Wentworth, Darrell M. Wilson, Carmella Evans-Molina, Diane Wherrett, Jay S. Skyler, Antoinette Moran, Jay M. Sosenko

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

OBJECTIVE We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants. RESEARCH DESIGN AND METHODS Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) baseline Index60 <1.00 OGTTs with an incident Index60 ≥1.00 OGTT. Incident dysglycemic OGTTs were divided into those with (DYS/IND+) and without (DYS/IND2) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS2) concomitant dysglycemia. RESULTS The cumulative incidence for type 1 diabeteswas greater after IND/DYS2than after DYS/IND2(P < 0.01).Within the normoglycemic cohort, the cumulative incidence of type 1 diabeteswas higher afterDYS/IND+ than afterDYS/IND2(P < 0.001),whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS2 did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS2 than for DYS/IND2 (P < 0.001). Hazard ratios (HRs) ofDYS/IND2with age and 30- to 0-min C-peptidewere positive (P < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse (P < 0.001 for both). In contrast, HRs of IND/DYS2 and type 1 diabetes with age and 30- to 0-min C-peptide were consistent (all inverse [P < 0.01 for all]). CONCLUSIONS The findings suggest that incident dysglycemia without Index60 ≥1.00 is a suboptimal prediagnostic end point for type 1 diabetes. Measures that include both glucose and C-peptide levels, suchas Index60≥1.00, appear better suited as prediagnostic end points.

Original languageEnglish (US)
Pages (from-to)1494-1499
Number of pages6
JournalDiabetes care
Volume40
Issue number11
DOIs
StatePublished - Nov 1 2017

ASJC Scopus subject areas

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

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    Nathan, B. M., Boulware, D., Geyer, S., Atkinson, M. A., Colman, P., Goland, R., Russell, W., Wentworth, J. M., Wilson, D. M., Evans-Molina, C., Wherrett, D., Skyler, J. S., Moran, A., & Sosenko, J. M. (2017). Dysglycemia and Index60 as prediagnostic end points for type 1 diabetes prevention trials. Diabetes care, 40(11), 1494-1499. https://doi.org/10.2337/dc17-0916