162-LB: Impact of High-Fat Meal on Circulating microRNA in Youth with T1DM

Abstract

MicroRNA (miRNA) are small non-coding RNAs that impact translation via degrading or repressing mRNA. From animal models, circulation abundance of miRNA is impacted by feeding. The goal of this project was to compare levels of specific circulating miRNAs between youth with T1DM and controls and the impact of a high fat meal on miRNA abundance. Fourteen youth (6 females, 8 males) with T1DM and 29 normal weight control youth (14 females, 15 males) ingested a milkshake with 830 kcal; 36% carbohydrate, 54% fat (31 grams of saturated fat), and 10% protein. Circulating miRNAs (miR-122, 126, and 130b) at baseline and 150 minutes post-ingestion were measured by qPCR. The group with T1DM had a median A1c of 8.4% (7.4, 8.9) with an average duration of 7 years. At baseline, miR-126 tended to be higher in the youth with T1DM (47%, p=0.072). In pooled groups, all three miRNAs decreased at 150 min (miR-122: -21%, p=0.036; miR-126: -37%, p=0.001; and miR-130b: -33%, p=0.023). Within the control group, miR-122 and miR-126 decreased 26% and 28% from baseline (p=0.037 and p=0.035, respectively). Within the T1DM group, miR-126 and miR-130b decreased 49% and 50% from baseline (p=0.007 and p=0.011, respectively). The decrease in miR-122 from baseline was correlated with the total energy expenditure for the meal (r=0.-0.379, p=0.017) and insulin under the curve (r=0.350, p=0.029). The decrease in miR-126 and miR-130b were negatively correlated with glucose area under the curve (r=-0.369 and -0.358, p=0.021 and 0.025, respectively), and the decrease in miR-130b was negatively correlated with baseline NEFA (r= -0.328, p=0.042). miR-122 and 130b both target AMPK, which could alter lipid metabolism, thus explaining the associations with NEFA and energy expenditure. miR-126 is known to target both IRS1 and PI3K in the insulin signaling pathway, potentially explaining the association with glucose. It is clear that the circulating abundance of these miRNAs is reduced following a high fat meal, and that response may be modified by the presence of T1DM. Disclosure J.B. Tryggestad: None. A.M. Teague: None. K.R. Short: None. Funding Harold Hamm Diabetes Center; Ardmore Institute of Health