Alterations in NEFA trafficking rather than hyperandrogenism contribute to metabolic health in obese women with PCOS.

OBJECTIVE: To determine whether alterations in non-esterified free fatty acids (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between metabolically healthy (MHO-PCOS) and metabolically unhealthy (MUO-PCOS) obese PCOS women.

DESIGN: Prospective cross-sectional study.

SUBJECTS: One hundred-and-twenty-five obese PCOS women.

INTERVENTION: Consecutive obese (BMI≥30 kg/m2) oligo-ovulatory PCOS women (n=125) underwent oGTT and a subgroup of 16 participants underwent modified frequently samples intravenous glucose tolerance test (mFSIVGTT), to determine insulin action and NEFA dynamics.

MAIN OUTCOME MEASURES: Degree of IR in adipose tissue (AT) basally (Adipo-IR) and dynamically (NEFAnadir, TIMEnadir, and %NEFAsupp); lipolysis rate (SNEFA) and NEFA uptake rate (KNEFA); whole-body insulin action (AIRg, Si, Sg, and DI); and HA (hirsutism score, testosterone [total, free], DHEAS).

RESULTS: 85 (68%) subjects were MUO-PCOS and 40 (32%) MHO-PCOS by HOMA-IR. MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, WHR, HA and lipoprotein levels. By mFSIVGTT, 8 MUO-PCOS subjects had lesser Si, KNEFA , and %NEFAsupp , and greater TIMEnidar , NEFAnidar and Adipo-IR, than 8 MHO-PCOS, but similar fasting NEFA and SNEFA . MUO-PCOS had higher HOMA-β% and fasting insulin than MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with NEFAnadir , weakly and negatively with TIMEnadir , and positively with KNEFA and NEFAsupp , in MUO-PCOS only.

CONCLUSION: Independent of age and BMI, MUO-PCOS women have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, than MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese PCOS women.