Glucose and C-Peptide Changes in the Perionset Period of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1

OBJECTIVE—We examined metabolic changes in the period immediately after the diagnosis of type 1 diabetes and in the period leading up to its diagnosis in Diabetes Prevention Trial–Type 1 (DPT-1) participants. RESEARCH DESIGN AND METHODS—The study included oral insulin trial participants and parenteral insulin trial control subjects (n = 63) in whom diabetes was diagnosed by a 2-h diabetic oral glucose tolerance test (OGTT) that was confirmed by another diabetic OGTT within 3 months. Differences in glucose and C-peptide levels between the OGTTs were assessed. RESULTS—Glucose levels increased at 90 (P = 0.006) and 120 min (P < 0.001) from the initial diabetic OGTT to the confirmatory diabetic OGTT (mean ± SD interval 5.5 ± 2.8 weeks). Peak C-peptide levels fell substantially between the OGTTs (median change −14.3%, P < 0.001). Among the 55 individuals whose last nondiabetic OGTT was ∼6 months before the initial diabetic OGTT, peak C-peptide levels decreased between these two OGTTs (median change −14.0%, P = 0.052). Among those same individuals the median change in peak C-peptide levels from the last normal OGTT to the confirmatory OGTT (interval 7.5 ± 1.3 months) was −23.8% (P < 0.001). Median rates of change in peak C-peptide levels were 0.00 ng · ml(−1) · month(−1) (P = 0.468, n = 36) from ∼12 to 6 months before diagnosis, −0.10 ng · ml(−1) · month(−1) (P = 0.059, n = 55) from 6 months before diagnosis to diagnosis, and −0.43 ng · ml(−1) · month(−1) (P = 0.002, n = 63) from the initial diabetic OGTT to the confirmatory diabetic OGTT. CONCLUSIONS—It seems that postchallenge C-peptide levels begin to decrease appreciably in the 6 months before diagnosis and decrease even more rapidly within 3 months after diagnosis.