1174-P: Circulating MicroRNA in Youth with Type 1 Diabetes in Response to a Meal Challenge

Circulating abundance of microRNAs (miRNA) are altered in youth with type 1 diabetes (T1D) and in response to a high fat meal, but whether T1D modifies the miRNA response to a meal is unknown. We identified miRNAs altered in youth with T1D compared to youth without T1D (control) after a high fat meal challenge, a novel approach to understanding how metabolic stress responses may be altered by T1D. Each group had 6 girls and 6 boys, similar in age (17.9±1.5 y), with normal BMI (65±22 and 43±15 percentile, respectively). Serum samples were collected at baseline and 150 min after meal consumption. The meal composition was 75 g carbohydrate, 50 g fat (31 g saturated fat), and 20 g protein. Participants with T1D administered insulin before the meal. Total RNA was extracted using the Qiagen miRNeasy Serum/Plasma Advanced Kit. The Nanostring nCounter Human v3 miRNA Panel was used for miRNA profiling. Abundance values were normalized for the number of reads across all samples. The data were fit to a linear model, and an empirical Baysean test was used to determine differences in circulating miRNAs between groups at baseline and after meal consumption. Significance was set as fold change greater than 0.5 with p<0.05. At baseline 17 miRNA species were lower in abundance in the youth with T1D while 16 were higher. In response to the meal, 3 miRNAs declined, and 4 miRNAs increased in the control group while 4 miRNAs declined, and 2 miRNAs increased in the T1D group. Compared to the control group, the T1D group had 19 miRNAs with smaller post-meal changes and 10 with larger changes. The changes in miR-573, miR-655-3p, and miR-769-5p were negatively correlated with glucose AUC and HbA1c, while the change in miR-3192-5p was positively correlated with glucose AUC and HbA1c. These finding show that T1D modifies responses in serum miRNA abundance following a high fat meal, and some of those differences are associated with glycemia. We postulate that the changes in miRNAs are mediated by glycemia, and future investigations will explore this mechanism.