Effects of endogenous androgens and abdominal fat distribution on the interrelationship between insulin and non-insulin-mediated glucose uptake in females

J Clin Endocrinol Metab. 2013 Apr;98(4):1541-8. doi: 10.1210/jc.2012-2937. Epub 2013 Feb 28.

Abstract

Background: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship.

Objectives: The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution.

Participants: Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography.

Main outcome measures: Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured.

Results: PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively.

Conclusion: The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Abdominal Fat / drug effects*
  • Administration, Intravenous
  • Adult
  • Androgens / blood*
  • Androgens / metabolism
  • Androgens / pharmacology*
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Body Composition / drug effects*
  • Body Fat Distribution*
  • Case-Control Studies
  • Female
  • Glucose / administration & dosage
  • Glucose / pharmacokinetics*
  • Glucose Tolerance Test
  • Humans
  • Insulin / pharmacology*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / metabolism
  • Sex Factors
  • Young Adult

Substances

  • Androgens
  • Blood Glucose
  • Insulin
  • Glucose