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The Pathological Evolution of Glucose Response Curves During the Progression to Type 1 Diabetes in the TrialNet Pathway to Prevention Study
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posted on 2020-09-08, 17:32 authored by Heba M. Ismail, Mario A. Cleves, Ping Xu, Ingrid M. Libman, Dorothy J. Becker, Jennifer B. Marks, Jay S. Skyler, Jerry P. Palmer, Jay M. Sosenko, Type 1 Diabetes TrialNet Study GroupObjective: Glucose response
curves (GRCs) during oral glucose tolerance tests (OGTTs) are predictive of
type 1 diabetes. We performed a longitudinal analysis in pancreatic
autoantibody positive (Ab+) individuals to
assess: 1) characteristic GRC changes during progression to type 1 diabetes, and
2) GRC changes in relation to β-cell function changes and to combined glucose and C-peptide response curve
(GCRC) changes. Research Design and
Methods: Among Ab+ individuals with serial OGTTs in the TrialNet Pathway to
Prevention study, GRC changes from first to last OGTTs were compared between
progressors (n=298) to type 1 diabetes and non-progressors (n=2216). GRC
changes from last before diagnosis to diagnostic OGTTs were studied in
progressors. Results: GRCs changed more frequently from Biphasic (2
peaks) to Monophasic (1 peak) GRCs between
first and last OGTTs in progressors than in non-progressors [75.4% vs.
51.0%; p<0.001]. In contrast, progressors changed less frequently from Monophasic
to Biphasic than non-progressors [12.6% vs. 30.6%; p <0.001]. Monotonic (continuous
increase) GRCs were present in 47.7% of
progressors at diagnosis. The early (30-0
min) C-peptide response decreased in progressors changing from Biphasic to Monophasic between first and last OGTTs
(p<0.001) and from Monophasic to Monotonic between last and diagnostic OGTTs
(p<0.001). Conversely, the early C-peptide response increased among non-progressors changing from Monophasic to Biphasic (p<0.001). Changes in GRCs were related to changes in GCRCs.
Conclusions: Characteristic GRC changes, Biphasic to Monophasic to
Monotonic, occur during the progression to type 1 diabetes. These GRC changes
correspond to decreasing β-cell function.