The effect of pioglitazone treatment on 15-epi-lipoxin A4 levels in patients with type 2 diabetes

Objectives: Arachidonic acid-derived eicosanoids (lipoxins and 15-epilipoxins) have a major role in resolution of inflammation. 15-epi-lipoxin A(4) (15-epi-LXA(4)) is a lipid mediator with strong anti-inflammatory and inflammation-resolving effects. We examined the effect of pioglitazone therapy on plasma 15-epi-LXA(4) in patients with type 2 diabetes (T2DM). Methods: T2DM patients (Age = 56 +/- 2 y, BMI = 33 +/- 1.8, HbA1c = 7.8 +/- 0.3%) not on thiazolidinedione therapy for at least 12 months were randomized to receive either pioglitazone 15 mg/daily for two months (PIO 15) or pioglitazone 15 mg/day for one month followed by a dose escalation to 30 mg/day for an additional one month (PIO 30). Results: PIO 15 increased plasma 15-epi-LXA(4) levels (0.63 +/- 0.06-1.05 +/- 0.08 ng/mL, p < 0.01) and adiponectin levels (6.4 +/- 0.3-10.1 +/- 0.7 mu g/mL, p < 0.001) and decreased fasting plasma glucose (125 +/- 8 -106 +/- 9 mg/dL, p < 0.05), free fatty acids (FFA) (414 +/- 46-320 +/- 38 mu mol/l, p < 0.05) and HOMA-IR (5.3 +/- 0.4 to 4.0 +/- 0.4, p < 0.05). Body weight (Delta = 0.2 kg) and HbA1c (7.4 +/- 0.2-7.1 +/- 0.2%) did not change significantly. PIO 30 treated patients had similar increase in plasma 15-epi-LXA(4) (0.64 +/- 0.10 -1.08 +/- 0.09 ng/mL, p < 0.01), and decrease in plasma FFA (423 +/- 42-317 +/- 40 mu mol/l, p < 0.05) despite a greater increase in plasma adiponectin (6.5 +/- 0.4-15.5 +/- 0.7 ug/mL, p < 0.001) and a greater reduction in HbA1c (8.7 +/- 0.5-7.4 +/- 0.3%, p < 0.01), FPG (159 +/- 16-120 +/- 10 mg/dL, p < 0.01), and HOMA-IR (6.6 +/- 0.8-4.4 +/- 0.4, p < 0.005). Furthermore, PIO 30 treated patients had a significant increase in body weight (Delta = 1.7 kg, p < 0.02). Conclusion: In T2DM, low dose pioglitazone (15 mg/day) increases 15-epi-LXA4 and adiponectin levels in the absence of significant changes in body weight. Dose escalation of pioglitazone to 30 mg/day is associated with a similar increase in 15-epi-LXA4 despite a greater increase in plasma adiponectin concentrations. (C) 2012 Elsevier Ireland Ltd. All rights reserved.