Glucose excursions between states of glycemia with progression to type 1 diabetes in the diabetes prevention trial-type 1 (DPT-1).

Abstract

We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose. Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis. Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30- to 0-min C-peptide difference values changed little. Likewise, 30- to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001). Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early C-peptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.