Adipose Insulin Resistance in Normal-Weight Women With Polycystic Ovary Syndrome

CONTEXT: Normal-weight women with polycystic ovary syndrome (PCOS) may have adipose tissue insulin resistance (adipose-IR). OBJECTIVE: To examine whether adipose-IR and subcutaneous (SC) abdominal adipose stem cell (ASC) gene expression are altered in normal-weight women with PCOS and correlated with hyperandrogenemia and/or whole-body IR. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: Ten normal-weight women with PCOS and 18 control subjects matched for age and body mass index. INTERVENTION(S): Women underwent circulating hormone and metabolic measurements, IV glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S): Adipose-IR (fasting insulin × total fatty acid levels) and SC abdominal ASC gene expression were compared between groups and correlated with clinical outcomes. RESULTS: Adipose-IR was greater in women with PCOS than in control subjects (P < 0.01), with 29 pmol/L × mmol/L providing 94% specificity and 80% sensitivity in discriminating the two groups (P < 0.001). Adipose-IR positively correlated with serum androgen and log of fasting triglyceride (TG) levels, percentage of small adipocytes (P < 0.01, all correlations), and acute insulin response to glucose (P < 0.05); and negatively correlated with insulin sensitivity (Si; P < 0.025) and serum adiponectin levels (P < 0.05). Adjusting for serum androgens, adipose-IR correlations with Si and log TG levels remained significant. ASC genes were differentially expressed by the two groups. Expression of functionally critical genes was associated with serum testosterone and/or fasting insulin levels. CONCLUSION: Normal-weight women with PCOS have increased adipose-IR and altered ASC gene expression related to hyperandrogenism and IR.