title: Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.
abstract: BACKGROUND
  Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity.
  
  
  METHODS
  This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects.
  
  
  METHODS
  At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored.
  
  
  RESULTS
  Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63 × 10(-3) to 0.76 × 10(-3). This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP.
  
  
  CONCLUSIONS
  Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation.
  
  
  BACKGROUND
  ClinicalTrial.gov NCT01253928.
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Zanchi
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland; Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Tappy
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Kim-Anne
authors.initials: KA
authors.lastname: Lê
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Murielle
authors.initials: M
authors.lastname: Bortolotti
authors.affiliation: Department of Radiology, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Theumann
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Georges
authors.initials: G
authors.lastname: Halabi
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gauthier
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Claudine
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tremblay
authors.affiliation: Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Pauline Coti
authors.initials: PC
authors.lastname: Bertrand
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
authors.affiliation: Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Teta
mesh_terms: D054392:Adipokines / Q000097:blood*; D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000077205:Pioglitazone; D006435:Renal Dialysis; D050151:Subcutaneous Fat / Q000187:drug effects / Q000473:pathology; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D020738:Leptin; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone