Glucose and C-peptide changes in the perionset period of type 1 diabetes in the Diabetes Prevention Trial-Type 1

Abstract

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 approximately 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 x ml(-1) x month(-1) (P = 0.468, n = 36) from approximately 12 to 6 months before diagnosis, -0.10 ng x ml(-1) x month(-1) (P = 0.059, n = 55) from 6 months before diagnosis to diagnosis, and -0.43 ng x ml(-1) x 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.

Figure 1

A: Percent changes in glucose indexes after diagnosis. Shown are the medians for the percent changes of glucose indexes from the initial diabetic OGTT to the confirmatory diabetic OGTT. Glucose levels tended to increase, especially at the later time points of the OGTT. B: Percent changes in C-peptide indexes after diagnosis. Shown are the medians for the percent changes of C-peptide indexes from the initial diabetic OGTT to the confirmatory diabetic OGTT. With the exception of the fasting C-peptide, there was a >10% median decline for all of the indexes.

Figure 2

Association between change in peak C-peptide and time after diagnosis. Shown is the scatter plot for the association between the change in peak C-peptide levels and the time after diagnosis. The amount of decline becomes more substantial with increasing time after diagnosis. (An outlier was removed with a change in peak C-peptide of −8.8 ng/ml and a time after diagnosis of 8.0 weeks [r = −0.31, P = 0.014 with the outlier included.]) When an allowance was made for the peak C-peptide at the first diabetic OGTT, the slope for the difference in peak C-peptide versus time after diagnosis was −0.56 ng · ml⁻¹ · month⁻¹.

Figure 3

Rates of change in peak C-peptide in the perionset period. Shown are the rates of change of peak C-peptide levels according to intervals before and after diagnosis. C-peptide levels changed minimally between ∼12 and 6 months before diagnosis. There was a decline in the 6 months before diagnosis that was more substantial in the period after diagnosis.