127-OR: Changes in Adipocyte-Derived Exosomal MicroRNAs May Play a Role in the Progression from Obese Normoglycemia to Hyperglycemia/Diabetes

We previously showed that visceral adipocyte-derived exosomal microRNA content is pathologically altered in obesity to impair insulin receptor signaling. However, why some obese youth (± insulin resistance) remain normoglycemic, while others progress to hyperglycemia, is not fully understood. We hypothesize that compared to obese normoglycemic youth (ON), circulating adipocyte-derived exosomes from obese hyperglycemic youth (OH) are enriched for microRNAs targeting carbohydrate metabolism and this association is modified by the amount of visceral fat (VFAT). We conducted a cross-sectional analysis of 55 obese pubertal adolescents (12-17 years), who underwent OGTT, whole body DXA, and serum adipocyte-derived exosomal microRNA assays. Univariate and regression analyses compared ON and OH groups. MicroRNA profiles were evaluated via ANCOVA and ANOVA. ON (n=32) and OH (n=23) groups were similar for sex, age, race, pubertal stage, BMI, and fat mass (FM). However, OH had increased VFAT compared to ON (88.1±24.6cm2 vs. 71.4±21.6, p=0.01). Between OH and ON, 33 known mature human microRNAs were differentially expressed (p