title: Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in continuous ambulatory peritoneal dialysis patients--a randomized crossover trial.
abstract: BACKGROUND
  The aim of the present study was to investigate the effect of oral pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients.
  
  
  METHODS
  In this randomized crossover trial, 36 CAPD patients with serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week washout, the patients were switched to the alternative regimen. The primary endpoint was change in serum triglycerides during the PIO regimen compared with no PIO. Secondary endpoints included changes in other lipid levels, homeostatic model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive protein (CRP).
  
  
  RESULTS
  All 36 CAPD patients (age: 64 ± 11 years; 33% men; 27.8% with diabetes mellitus) completed the study. Comparing patients after PIO and no PIO therapy, we found no significant differences in mean serum triglycerides (3.83 ± 1.49 mmol/L vs 3.51 ± 1.98 mmol/L, p = 0.2). However, mean high-density lipoprotein (0.94 ± 0.22 mmol/L vs 1.00 ± 0.21 mmol/L, p = 0.004) and median total adiponectin [10.34 μg/mL (range: 2.59 - 34.48 μg/mL) vs 30.44 μg/mL (3.47 - 93.41 μg/mL), p < 0.001] increased significantly. Median HOMA-IR [7.51 (1.39 - 45.23) vs 5.38 (0.97 - 14.95), p = 0.006], mean fasting blood glucose (7.31 ± 2.57 mmol/L vs 6.60 ± 2.45 mmol/L, p = 0.01), median CRP [8.78 mg/L (0.18 - 53 mg/L) vs 3.50 mg/L (0.17 - 26.30 mg/L), p = 0.005], and mean resistin (32.70 ± 17.17 ng/mL vs 28.79 ± 11.83 ng/mL, p = 0.02) all declined. The PIO was well tolerated, with only one adverse event: lower-extremity edema in a patient with low residual renal function.
  
  
  CONCLUSIONS
  Blood triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD patients, but parameters of dysmetabolism were markedly improved, including insulin resistance, inflammation, and adipokine balance, suggesting that PIO could be of value for this high-risk patient group. Larger, more definitive studies are needed to confirm these findings.
authors.affiliation: Department of Nephrology, Huashan Hospital of Fudan University, Shanghai, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Qiong-hong
authors.initials: QH
authors.lastname: Xie
authors.forename: Huai-zhou
authors.initials: HZ
authors.lastname: You
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Chuan-ming
authors.initials: CM
authors.lastname: Hao
authors.forename: Shan-yan
authors.initials: SY
authors.lastname: Lin
authors.forename: Tong-ying
authors.initials: TY
authors.lastname: Zhu
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002097:C-Reactive Protein; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007333:Insulin Resistance; D052439:Lipid Metabolism Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D000077205:Pioglitazone; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D054392:Adipokines; D015415:Biomarkers; D007004:Hypoglycemic Agents; D008055:Lipids; D045162:Thiazolidinediones; D014280:Triglycerides; D002097:C-Reactive Protein; D000077205:Pioglitazone