Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome.

study questionAre differences in metabolic dysfunction between polycystic ovary syndrome (PCOS) and control women related to differences in their fat to lean mass (F/L) ratio? SUMMARY ANSWER: Compared with controls of similar body mass index (BMI), women with PCOS demonstrate adverse body composition characterized by increased whole body fat relative to lean mass (i.e. a higher F/L ratio), which is associated with differences in metabolic dysfunction between the two groups. WHAT IS KNOWN ALREADY: Previous studies examining body composition and insulin resistance (IR) in PCOS have yielded conflicting results. Excess total fat mass (i.e. fat mass index [fat BMI]) correlates with IR, whereas increased total lean mass (i.e. lean BMI) has been associated with higher insulin sensitivity. However, the role of the F/L ratio, which integrates the antagonistic effects of both fat and lean mass depots, on IR in PCOS, has not been investigated. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cross-sectional study of 120 women between the ages of 22-44 years to study the relation of the F/L ratio with measures of insulin action and secretion in both steady and dynamic states. PARTICIPANTS/MATERIALS, SETTING,

methodsSixty PCOS (by NIH, 1990 criteria) and 60 control (age, race and BMI-matched) women were prospectively studied for body composition (by bioelectrical impedance analysis [BIA]) and basal IR and insulin secretion by the homeostasis model assessment (HOMA-IR and HOMA-%β-cell function, respectively) in a tertiary care academic referral center. A subset of 12 PCOS and 12 matched control women also underwent a modified frequently sampled intravenous glucose tolerance test (FSIVGTT) to determine glucose uptake and insulin secretion in dynamic state. MAIN RESULTS AND THE ROLE OF CHANCE: Our results indicate that women with PCOS demonstrated greater degrees of hyperandrogenism, and higher waist-to-hip ratio (WHR), %body fat, fat BMI, F/L, fasting insulin levels, and HOMA-IR and HOMA-%β-cell values, than controls. In models adjusted for WHR and free testosterone and diagnostic groups, fasting insulin levels, HOMA-IR, and HOMA-%beta cell function were positively related to the F/L ratio. A positive relationship was also found in both study groups between F/L and the FSIVGTT measures insulin sensitivity (Si) and acute insulin response to glucose (AIRg). The F/L tended to negatively correlate with glucose effectiveness or non-insulin-mediated glucose transport (Sg) only in PCOS women. LIMITATIONS, REASONS FOR CAUTION: Regional tissue sub-compartments, which have been shown to have potential independent associations with metabolic variables, cannot be determined by bioelectrical impedance analysis (BIA). WIDER IMPLICATIONS OF THE

findingsThe current results suggest that BIA could be used to assess F/L in place of dual energy X-ray absorptiometry (DXA) in research protocols, and that F/L could possibly be used as an alternative to WHR as a surrogate marker of metabolic dysfunction in clinical practice. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants R01-DK073632 and R01-HD29364 from the NIH and an endowment of the Helping Hand of Los Angeles, Inc. (to R.A.). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.