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

Hum Reprod. 2014 Jul;29(7):1508-17. doi: 10.1093/humrep/deu096. Epub 2014 May 9.

Abstract

Study question: Are 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, methods: Sixty 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 findings: The 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adipose Tissue*
  • Adult
  • Body Composition*
  • Body Mass Index
  • Case-Control Studies
  • Cross-Sectional Studies
  • Electric Impedance
  • Female
  • Glucose Tolerance Test
  • Homeostasis
  • Humans
  • Hyperandrogenism / complications
  • Insulin / metabolism
  • Insulin Resistance
  • Metabolic Syndrome / physiopathology*
  • Obesity / pathology
  • Polycystic Ovary Syndrome / physiopathology*
  • Prospective Studies
  • Waist-Hip Ratio
  • Young Adult

Substances

  • Insulin