title: Pancreatic β-cell dysfunction in polycystic ovary syndrome: the role of metformin.
abstract: OBJECTIVE
  To determine whether the administration of 6 months of daily metformin treatment in women with polycystic ovary syndrome (PCOS) would significantly improve pancreatic β-cell function as measured by an increase in the disposition index.
  
  
  METHODS
  We enrolled women with PCOS from a private practice and from the Mount Sinai Hospital Endocrinology Clinic. All patients underwent frequently sampled intravenous glucose tolerance tests both on and off 500 to 1000 mg of twice daily metformin. Values of insulin sensitivity, glucose effectiveness, acute insulin response to glucose, and disposition index were calculated for each test. The product of acute insulin response to glucose and insulin sensitivity yielded the disposition index and estimated the degree of β-cell compensation for insulin resistance.
  
  
  RESULTS
  We enrolled 14 women. We observed no significant changes in insulin sensitivity, glucose effectiveness, or acute insulin response to glucose, disposition index, or distributed glucose at time 0 before or after metformin treatment. Patients with PCOS treated with metformin remained statistically on the same hyperbolic curve, which is consistent with previously reported results of the effect of metformin on β-cell function. In contrast, the proportional change in disposition index correlated significantly with the proportional change in insulin sensitivity. Patients whose insulin sensitivity decreased after treatment showed a proportional decrease in disposition index, while patients whose insulin sensitivity increased showed a proportional increase in disposition index.
  
  
  CONCLUSIONS
  Our findings suggest that acute insulin response to glucose does not proportionately change to match change in insulin sensitivity. Thus, there may be a β-cell defect in women with PCOS.
authors.affiliation: Mount Kisco Medical Group, Mount Kisco, New York, USA. ckmesser@gmail.com
authors.forename: Caroline
authors.initials: C
authors.lastname: Messer
authors.forename: Raymond
authors.initials: R
authors.lastname: Boston
authors.forename: Derek
authors.initials: D
authors.lastname: Leroith
authors.forename: Eliza
authors.initials: E
authors.lastname: Geer
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Miller
authors.forename: Marcelo
authors.initials: M
authors.lastname: Messer
authors.forename: Walter
authors.initials: W
authors.lastname: Futterweit
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D008687:Metformin