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Diabetes Care. 2017 Nov;40(11):1494-1499. doi: 10.2337/dc17-0916. Epub 2017 Aug 31.

Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials.

Author information

1
University of Minnesota, Minneapolis, MN natha039@umn.edu.
2
University of South Florida, Tampa, FL.
3
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL.
4
Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
5
Columbia University, New York, NY.
6
Vanderbilt University, Nashville, TN.
7
Stanford University, Stanford, CA.
8
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
9
University of Toronto, Toronto, Ontario, Canada.
10
University of Miami, Miami, FL.
11
University of Minnesota, Minneapolis, MN.

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/IND-) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS-) concomitant dysglycemia.

RESULTS:

The cumulative incidence for type 1 diabetes was greater after IND/DYS- than after DYS/IND- (P < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND- (P < 0.001), whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS- did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS- than for DYS/IND- (P < 0.001). Hazard ratios (HRs) of DYS/IND- with age and 30- to 0-min C-peptide were 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/DYS- 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, such as Index60 ≥1.00, appear better suited as prediagnostic end points.

PMID:
28860125
PMCID:
PMC5652585
DOI:
10.2337/dc17-0916
[Indexed for MEDLINE]
Free PMC Article

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