Role of the funding source: Funding from the NIH was used for support of the participating clinical centers and the coordinating center. The funding source did not participate in the collection or the analysis of the data.
BACKGROUND. The β cell killing that characterizes type 1 diabetes (T1D) is thought to begin years before patients present clinically with metabolic decompensation; however, this primary pathologic process of the disease has not been measured.
METHODS. Here, we measured β cell death with an assay that detects β cell–derived unmethylated insulin (
RESULTS. In at-risk subjects, those who progressed to T1D had average levels of unmethylated
CONCLUSION. We conclude that a blood test that measures unmethylated
TRIAL REGISTRATION. Clinicaltrials.gov NCT00097292.
FUNDING. Funding was from the NIH, the Juvenile Diabetes Research Foundation, and the American Diabetes Association.
Kevan C. Herold, Sahar Usmani-Brown, Tara Ghazi, Jasmin Lebastchi, Craig A. Beam, Melena D. Bellin, Michel Ledizet, Jay M. Sosenko, Jeffrey P. Krischer, Jerry P. Palmer
CONSORT diagram showing allocation of the study subjects.
The TrialNet Natural History study commenced in 2004. The number of subjects screened reflects the total number of subjects since enrollment. The first at-risk subject was enrolled in 2005 and the last was enrolled in 2008. The high-risk subjects were identified between 2010 and 2013. The diagram shows the allocation of subjects to the “at-risk” group that was prospectively followed and the “high-risk” group that was studied on 2 occasions.