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

Nathan, BM; Boulware, D; Geyer, S; Atkinson, MA; Colman, P; Goland, R; Russell, W; Wentworth, JM; Wilson, DM; Evans-Molina, C; Wherrett, D; Skyler, JS; Moran, A; Sosenko, JM; Type 1 Diabetes, TrialNet; Diabetes Prevention Trial-Type 1 Study, Groups

Author(s): Nathan, BM; Boulware, D; Geyer, S; Atkinson, MA; Colman, P; Goland, R; Russell, W; Wentworth, JM; Wilson, DM; Evans-Molina, C; Wherrett, D; Skyler, JS; Moran, A; Sosenko, JM; Type 1 Diabetes, TrialNet; Diabetes Prevention Trial-Type 1 Study, Groups;
Details: Publication Year 2017-11,Volume 40,Issue #11,Page 1494-1499
Journal Title: Diabetes Care
Publication Type: Journal Article
Abstract: OBJECTIVE: We assessed dysglycemia and an 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 30-0-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 30-0-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.
Publisher: American Diabetes Association
Research Division(s): Population Health And Immunity
PubMed ID: 28860125
Publisher's Version: https://doi.org/10.2337/dc17-0916
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-09-06 11:18:07

Last Modified: 2017-11-29 08:37:34