By employing a novel approach based on prediction and natural history, clinicians may be able to diagnose type 1 diabetes at an earlier stage of disease in some people, according to data published in Diabetes Care

In the article, the researchers noted that fasting glucose values and 2-hour glucose values are used to diagnose both type 1 and type 2 diabetes. However, these values were derived from findings in adults and may not always be appropriate for pediatric populations.

“This is particularly relevant to [type 1 diabetes], which commonly occurs in children. Moreover, current criteria do not take into account the evidence that the pathogenesis of [type 1 diabetes] begins years before it is diagnosed with standard glucose criteria. This suggests that other criteria can be used to diagnose [type 1 diabetes] at earlier stages of disease,” the researchers wrote.

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For their study, the researchers evaluated participants in the Diabetes Prevention Trial–Type 1 (DPT-1) and the TrialNet Natural History Study (TNNHS), all of whom were autoantibody-positive relatives of patients with type 1 diabetes and are therefore already at a high risk for the disease.

A metabolic index — Type 1 Diabetes Diagnostic Index60 (Index60) — was developed from 2-hour oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-minute C-peptide and 60-minute glucose.

The researchers then compared OGTTs with Index60 ≥2.00 and a 2-hour glucose <200 mg/dL (Index60+Only) to Index60 <2.00 and 2-hour glucose ≥200 mg/dL OGTTs (2-hour glucose+Only) as criteria for type 1 diabetes.

C-peptide loss was evaluated from the first Index60+Only OGTT to diagnosis.

Results revealed significantly higher areas under receiver operating characteristic curves for Index60 vs. the 2-hour glucose (P<.001 for both DPT-1 and the TNNHS cohorts).

For diagnosis of type 1 diabetes, sensitivity was higher for Index60+Only, as compared with 2-hour glucose+Only OGTTs (DPT-1, 0.44 vs. 0.15; TNNHS, 0.26 vs. 0.17). Specificity was slightly higher for 2-hour glucose+Only OGTTs in the DPT-1 (0.97 vs. 0.91), but there was no difference in the TNNHS (0.98 for both), according to the data.

The researchers also found higher positive and negative predictive values for Index60+Only OGTTs in both DPT-1 and TNNHS.

At each OGTT time point from the first Index60+Only to time of standard diagnosis, postchallenge C-peptide levels decreased. Data also demonstrated significantly different C-peptide and glucose patterns between Index60+Only and 2-hour glucose+Only OGTTs.

“Whether Index60 or another measure is used, it appears that an approach based on prediction and natural history can aid in diagnosing individuals at an earlier stage of disease,” the researchers wrote. “This approach will become increasingly important as preventive treatments for [type 1 diabetes] are assessed and ultimately implemented.”


  1. Sosenko JM et al. Diabetes Care. 2014;doi: 10.2337/dc14-1813.