MON-223 Adipose Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and oligo-ovulation associated with insulin resistance (IR). Adipose-IR may underlie this PCOS phenotype and could contribute to IR by impairing insulin-mediated glucose uptake and/or lipogenesis, while diminishing insulin suppression of lipolysis. The present study examined whether adipose-IR, defined as the product of fasting circulating free fatty acid and insulin levels (1), was increased in normal-weight PCOS versus age-/BMI-balanced normo-androgenic ovulatory (control) women and, if so, whether it correlated with insulin sensitivity (Si) as measured by frequently-sampled intravenous glucose tolerance testing (FSIVGTT) and/or hyperandrogenism. Ten normal-weight PCOS women (by NIH criteria) and 18 controls (19-35 years; 19-25 kg/m(2)) of non-Hispanic Caucasian descent underwent serum hormone/metabolic measurements, FSIVGTT, total body dual-energy x-ray absorptiometry, and subcutaneous (SC) abdominal fat biopsy. Circulating hormone/metabolite levels, adipose-IR, Si, acute insulin response to glucose (AIRg), body fat distribution and adipocyte size distribution were compared between female types using Student’s t-test. Partial correlation coefficients examined associations between adipose-IR and outcome variables, adjusting for serum androgen levels. PCOS women exhibited greater serum LH, androstenedione (A4), total testosterone (T) and free (f) T levels than controls (P<0.05, all parameters), and demonstrated trends for increased abdominal adiposity (P=0.06) and serum triglyceride (TG) levels (P=0.09) with low-normal Si values. PCOS women also had greater (P=0.007) adipose-IR than controls, with a value of 29 pM/L*mM/L providing 94% specificity (95% CI 84%-100%) and 80% sensitivity (95% CI 55%-100%) in discriminating PCOS subjects from controls (AUC=0.81, 95% CI 0.61-1.00, P<0.001). In all women combined, adipose-IR negatively correlated with Si (P=0.01) and positively correlated with serum A4 (P=0.002), total T (P=0.004), fT (P=0.001) and fasting TG (P=0.001) levels as well as with AIRg (P=0.03) and percent small SC abdominal adipocytes (P=0.01). Relationships of adipose-IR with Si (P=0.04) and with serum TG (P=0.01) levels remained after adjusting for serum total T and fT levels, respectively, while the other correlations lost significance. Thus, in normal-weight PCOS women, adipose-IR is intimately linked with dyslipidemia and is associated with reduced Si in part through hyperandrogenism. Reference: Sondergaard E, et al. JCEM 2017;102:1193. Sources of Research Support: NIH Grants and Santa Monica Bay Woman’s Club.