title: Pioglitazone treatment enlarges subcutaneous adipocytes in insulin-resistant patients.
abstract: BACKGROUND
  Obesity-related insulin resistance is associated with an increase in adipocyte size. In rodent models, treatment with the insulin-sensitizers thiazolidinediones (TZDs) leads to the appearance of small, insulin-sensitive adipocytes. Whether such TZD-dependent morphological changes occur in adipose tissue of insulin-resistant patients is unclear.
  
  
  OBJECTIVE
  The objective of the study was to study the effects of treatment with the TZD pioglitazone on sc adipose tissue morphology and function in insulin-resistant subjects.
  
  
  METHODS
  This was a placebo-controlled, randomized crossover study.
  
  
  METHODS
  The study was conducted at a university medical center.
  
  
  METHODS
  Twelve adult patients with congenital adrenal hyperplasia (CAH) characterized by insulin resistance were included in this study.
  
  
  METHODS
  After a 4-wk run-in phase, patients were treated with pioglitazone (45 mg/d) followed by placebo, each for 16 wk or vice versa.
  
  
  METHODS
  After both placebo and pioglitazone treatment, insulin sensitivity was determined by hyperinsulinemic euglycemic clamp and abdominal sc adipose tissue was obtained to measure adipocyte cell surface and expression of genes involved in glucose uptake and inflammation.
  
  
  RESULTS
  Pioglitazone treatment significantly improved the insulin sensitivity index (placebo: 0.35 +/- 0.16 micromol/kg . min per milliunit per liter; pioglitazone 0.53 +/- 0.16 micromol/kg . min per milliunit per liter, P < 0.001) and increased mRNA expression levels of adiponectin and glucose transporter-4 in adipose tissue. The increase in insulin sensitivity was accompanied by a significant enlargement of the sc adipocyte cell surface (placebo: 2323 +/- 725 microm(2); pioglitazone 2821 +/- 885 microm(2), P = 0.03).
  
  
  CONCLUSIONS
  In the human situation, treatment of insulin-resistant subjects with pioglitazone improves insulin sensitivity, whereas at the same time, sc adipocyte cell surface increases.
authors.affiliation: Departments of General Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. t.koenen@aig.umcn.nl
authors.forename: Tim B
authors.initials: TB
authors.lastname: Koenen
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.forename: Jeanne Margot
authors.initials: JM
authors.lastname: Kroese
authors.forename: Ad R
authors.initials: AR
authors.lastname: Hermus
authors.forename: Fred C G
authors.initials: FC
authors.lastname: Sweep
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Laak
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
authors.forename: Lambertus J H
authors.initials: LJ
authors.lastname: van Tits
authors.forename: Rinke
authors.initials: R
authors.lastname: Stienstra
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology*; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D018592:Cross-Over Studies; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000473:pathology; D000077205:Pioglitazone; D010919:Placebos; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D045162:Thiazolidinediones; D000077205:Pioglitazone