A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history

Abstract

Objective: We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals.

Research design and methods: Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only) were compared with Index60 <2.00 and 2-h glucose ≥200 mg/dL (2hglu+Only) OGTTs as criteria for T1D. Individuals were assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis.

Results: Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range -22 to -34% in DPT-1 and -14 to -27% in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs.

Conclusions: An approach based on prediction and natural history appears to have utility for diagnosing T1D.

Figure 1

Shown are mean C-peptide levels from the first Ind60+Only OGTT exceeded during follow-up to diagnosis in DPT-1. There was a marked decline in C-peptide levels at each of the postchallenge time points.

Figure 2

Panel A shows mean C-peptide levels for time points of Ind60+Only OGTTs and 2hglu+Only OGTTs in DPT-1. The C-peptide levels of the Ind60+Only OGTTs were much lower. Panel B shows mean glucose values for time points of Ind60+Only OGTTs and 2hglu+Only OGTTs in DPT-1. The glucose values tended to be higher at the earlier time points in the Ind60+Only OGTTs and higher at the later OGTT time points in the 2hglu+Only OGTTs.