Plasma miRNAs May Be Associated with Waist Circumference and Insulin Resistance among Women with Polycystic Ovary Syndrome-Pilot Study

Background: Insulin resistance (IR) and central obesity are common in PCOS, but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of tissue gene expression that may contribute to the pathogenesis of IR and central adiposity in PCOS. Methods: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n=11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR) -adjusted cutoff p<0.1 to adjust for multiple testing. We used the miRDB’s Gene Ontology (GO) tool to identify predicted pathways for top hits. Results: Participants were 27.9 years old on average with mean BMI 32.5 kg/m2. At an FDR<0.1, lower levels of miR-1294 were associated with higher waist circumference (β = -0.10, FDR=0.095) . While no miRNAs were associated with HOMA-IR at our predetermined cut off, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at p<0.01 (Table 1) . Pathways identified in the GO analysis of miR-1294 include “negative regulation of insulin receptor signaling” (p=0.019) . Conclusions: Plasma miRNAs may be associated with IR and central obesity among PCOS patients. Disclosure P. Wander: None. D. Enquobahrie: None. T. Bammler: None. J. Macdonald: None. S. Srinouanprachanh: None. T. Kaleru: None. D. Khakpour: None. S. Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas, Insulet Corporation, Insulet Corporation. Funding NIDDK (K08103945)