Previous studies have inferred that type 2 diabetes diagnosed during adolescence is more fulminant compared to type 2 diabetes diagnosed during adulthood. One hypothesis to explain this disparity is the exaggerated loss of the insulin-producing β-cells in the pancreas. The only known significant source of unmethylated insulin DNA is through the death of β-cells; therefore, the ratio of serum unmethylated to methylated (U/M) insulin DNA, as measured by droplet digital PCR (ddPCR), is predicted to be proportional to the degree of β cell death. While this method has been explored to identify those at risk for type 1 diabetes, it has not been explored to characterize adolescents with type 2 diabetes. Some degree of β-cell loss may account for the exaggerated decompensation in glucose control over time seen in adolescents. The purpose of this pilot study was to determine the extent of β-cell death in adolescents with type 2 diabetes using this novel biomarker. We recruited 18 participants between the ages of 10 and 18 years with an established diagnosis of type 2 diabetes for a single fasting study visit. Genomic DNA was isolated from each participant and was templated for ddPCR using two different primer/probe sets (reported previously by Miramira and colleagues) that discriminated DNA from β-cell sources (unmethylated) and from non-β-cell peripheral tissues (methylated). The U/M ratio was inversely correlated with age (r=-0.72, p<0.001) and with age at diagnosis (r=-0.56, p=0.015) via Spearman correlation. These results suggest that younger adolescents with type 2 diabetes may exhibit more extensive β-cell death compared to older adolescents and that adolescents diagnosed at a younger age may exhibit more extensive β-cell death compared to those diagnosed at an older age as indicated by a higher ratio of U/M insulin DNA.
D.S. Hsia: None. S. Mercer: None. J. Collier: None. W.D. Johnson: None. K. Mccormick: None.
National Institute of General Medical Sciences (U54GM104940); National Center for Advancing Translational Sciences (UL1TR001417)