This biomarker assay characterizes islet beta cell death by quantifying differentially methylated preproinsulin (INS) DNA with digital PCR. The assay can distinguish methylated and unmethylated cytosine at position -69 bp, is linear across several orders of magnitude, provides absolute quantitation of DNA copy numbers, and can be applied to samples of human serum from individuals with new-onset type 1 diabetes and disease-free controls.