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

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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

Bibliographical note

Funding Information:
Funding.The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the cooperative agreements U01-DK-061010, U01-DK-061034, U01-DK-061042, U01-DK-061058, U01-DK-085465, U01-DK-085453, U01-DK-085461, U01-DK-085466, U01-DK-085499, U01-DK-085504, U01-DK-085509, U01-DK-103180, U01-DK-103153, U01-DK-085476, U01-DK-103266, U01-DK-103282, U01-DK-106984, U01-DK-106994, U01-DK-107013, U01-DK-107014, and UC4-DK-106993; JDRF; the Victorian State Government Operational Infrastructure Support Program; and the National Health and Medical Research Council Research Institute Infrastructure Support Scheme.

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