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.

Figure 1

— Median levels of homeostatic model assessment of insulin resistance (HOMA-IR) in the groups during each phase of the study. Group A received oral pioglitazone 15 mg once daily for 12 weeks, and then after a washout period of 4 weeks, they received no pioglitazone for 12 weeks. Conversely, group B received no pioglitazone for 12 weeks, and then after a washout period of 4 weeks, they received pioglitazone for 12 weeks.

Figure 2

— Median levels of C-reactive protein (CRP) in the groups during each phase of the study. Group A received oral pioglitazone 15 mg once daily for 12 weeks, and then after a washout period of 4 weeks, they received no pioglitazone for 12 weeks. Conversely, group B received no pioglitazone for 12 weeks, and then after a washout period of 4 weeks, they received pioglitazone for 12 weeks.

Figure 3

— Median levels of adiponectin in the groups during each phase of the study. Group A received oral pioglitazone 15 mg once daily for 12 weeks, and then after a washout period of 4 weeks, they received no pioglitazone for 12 weeks. Conversely, group B received no pioglitazone for 12 weeks, and then after a washout period of 4 weeks, they received pioglitazone for 12 weeks.