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

• Published in: PloS one Vol. 9; no. 10; p. e109134
• Main Authors: Zanchi, Anne, Tappy, Luc, Lê, Kim-Anne, Bortolotti, Murielle, Theumann, Nicolas, Halabi, Georges, Gauthier, Thierry, Mathieu, Claudine, Tremblay, Sylvie, Bertrand, Pauline Coti, Burnier, Michel, Teta, Daniel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.10.2014; Public Library of Science (PLoS)
• Subjects: Adipokines - blood; Adiponectin; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - pathology; Adult; Anthropometry; Blood cholesterol; Body composition; Body Composition - drug effects; Body fat; Body weight; Cholesterol; Chronic kidney failure; Computed tomography; Cross-Over Studies; Diabetes; Diabetes mellitus; Dialysis; Double-Blind Method; Dual energy X-ray absorptiometry; End-stage renal disease; Endocrinology; Ethics; Fasting - blood; Female; Gene expression; Glucose; Glucose - metabolism; Health risks; High density lipoprotein; Homeostasis - drug effects; Hospitals; Humans; Hypoglycemic agents; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - pathology; Kidney diseases; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - therapy; Leptin; Leptin - blood; Liver - drug effects; Liver - metabolism; Maintenance; Male; Markers; Medical research; Medicine; Medicine and Health Sciences; Metabolism; Middle Aged; Mortality; Muscles; Nephrology; Peritoneal dialysis; Physiological aspects; Physiology; Pilot Projects; Pioglitazone; Renal Dialysis; Secretion; Sensitivity; Subcutaneous Fat - drug effects; Subcutaneous Fat - pathology; Thiazolidinediones - adverse effects; Thiazolidinediones - pharmacology; Switzerland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109134

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. This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. 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. 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. 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. ClinicalTrial.gov NCT01253928.