The Pathological Evolution of Glucose Response Curves During the Progression to Type 1 Diabetes in the TrialNet Pathway to Prevention Study.

Objective: 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 individuals to assess ) characteristic GRC changes during progression to type 1 diabetes and ) 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 antibody-positive individuals with serial OGTTs in the TrialNet Pathway to Prevention study, GRC changes from first to last OGTTs were compared between progressors ( = 298) to type 1 diabetes and nonprogressors ( = 2,216). GRC changes from last OGTT before diagnosis to diagnostic OGTTs were studied in progressors.

Results: GRCs changed more frequently from biphasic (two peaks) to monophasic (one peak) GRCs between first and last OGTTs in progressors than in nonprogressors (75.4% vs. 51.0%, respectively; < 0.001). In contrast, GRCs of progressors changed less frequently from monophasic to biphasic than those of nonprogressors (12.6% vs. 30.6%; < 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 with GRCs changing from biphasic to monophasic between first and last OGTTs ( < 0.001) and from monophasic to monotonic between last and diagnostic OGTTs ( < 0.001). Conversely, the early C-peptide response increased among nonprogressors with GRCs changing from monophasic to biphasic ( < 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.