A comparison of the baseline metabolic profiles between Diabetes Prevention Trial-Type 1 and TrialNet Natural History Study participants

Abstract

Objective: We assessed whether differing autoantibody screening criteria for type 1 diabetes (T1D) prevention trials result in different baseline metabolic profiles of those who screen positive.

Methods: Diabetes Prevention Trial-Type 1 (DPT-1) participants were screened for islet cell autoantibodies, whereas TrialNet Natural History Study (TNNHS) participants were screened for biochemical autoantibodies. In both studies, those determined to be autoantibody positive underwent baseline oral glucose tolerance tests (OGTTs) in which glucose and C-peptide were measured.

Results: The percentage of those with an OGTT in the diabetic range was higher among the DPT-1 participants (10.0% of 956 vs. 6.4% of 645, p < 0.01). In a logistic regression analysis with adjustments for age and gender, the difference persisted (p < 0.01). Among those in the non-diabetic range (n = 860 for DPT-1 and n = 604 for the TNNHS), glucose levels were similar at all time points, except for higher fasting glucose levels in the TNNHS participants (p < 0.001). There was a higher percentage of impaired fasting glucose (IFG) in the TNNHS participants (10.9 vs. 6.7%, p < 0.01); however, with adjustments for age and gender, there was no longer a significant difference. There was no significant difference in the percentages with impaired glucose tolerance. C-peptide levels were much lower in the DPT-1 cohort at all OGTT time points (p < 0.001 for all).

Discussion: Differing criteria for autoantibody screening can result in marked differences in the baseline metabolic profiles of prospective participants of T1D prevention trials.

Figure 1

This shows the percentage of individuals whose baseline OGTTs were in the diabetic range for DPT-1 and the TNNHS. The percentage was higher among the DPT-1 participants.

Figure 2

This shows the percentage of individuals whose baseline OGTTs were classified as IFG (A) and IGT (B) for DPT-1 and the TNNHS. Those with glucose levels in the diabetic range were excluded. Although the percentage was higher in the raw data for the TNNHS (p<0.01), the difference was not significant with adjustments for age and gender. There was little difference in the percentage with IGT.

Figure 2

This shows the percentage of individuals whose baseline OGTTs were classified as IFG (A) and IGT (B) for DPT-1 and the TNNHS. Those with glucose levels in the diabetic range were excluded. Although the percentage was higher in the raw data for the TNNHS (p<0.01), the difference was not significant with adjustments for age and gender. There was little difference in the percentage with IGT.

Figure 3

This shows C-peptide levels according to time points after the oral glucose challenge for participants in DPT-1 and the TNNHS. Those with glucose levels in the diabetic range were excluded. C-peptide levels were substantially lower for those in DPT-1 at every time point. For purposes of display the values for each time point were adjusted to males 15 years of age. They were calculated using coefficients derived from an analysis of covariance that included study (DPT-1 vs. the TNNHS), age, and gender as covariates.