The effect of pioglitazone treatment on 15-epi-lipoxin A4 levels in patients with type 2 diabetes
The effect of pioglitazone treatment on 15-epi-lipoxin A4 levels in patients with type 2 diabetes
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DOI：
10.1016/j.atherosclerosis.2012.04.016
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发表时间：
2012-07-01
期刊：
影响因子：
5.3
通讯作者：
Bajaj, Mandeep
中科院分区：
文献类型：
--
作者：
Gutierrez, Absalon D.;Sathyanarayana, Padma;Bajaj, Mandeep
目的：花生四烯酸衍生的类花生酸（脂氧素和15-表脂氧素）在炎症消退中起主要作用。15-epi-lipoxin A（4）（15-epi-LXA（4））是一种具有强烈抗炎和抗炎作用的脂质介质。我们检测了吡格列酮治疗对2型糖尿病（T2 DM）患者血浆15-epi-LXA（4）的影响。t2 dm患者（年龄= 56 +/- 2岁，BMI = 33 +/- 1.8，HbA 1c = 7.8 +/- 0.3%），未接受噻唑烷二酮治疗至少12个月，随机接受吡格列酮15 mg/天，持续2个月（PIO 15）或吡格列酮15 mg/天持续一个月，随后剂量递增至30 mg/天持续另外一个月（PIO 30）。PIO 15增加血浆15-epi-LXA（4）水平（0.63 +/- 0.06-1.05 +/- 0.08 ng/mL，p < 0.01）和脂联素水平（6.4 +/- 0.3-10.1 +/- 0.7 μ g/mL，p < 0.001）和空腹血糖降低（125 +/- 8 - 106 +/- 9 mg/dL，p < 0.05）、游离脂肪酸（FFA）（414 +/- 46-320 +/- 38 μ mol/l，p < 0.05）和HOMA-IR（5.3 +/- 0.4至4.0 +/- 0.4，p < 0.05）。体重（Delta = 0.2 kg）和HbA 1c（7.4 +/- 0.2-7.1 +/- 0.2%）无显著变化。PIO 30治疗患者的血浆15-epi-LXA水平也有类似的增加（4）（0.64 +/- 0.10 - 1.08 +/- 0.09 ng/mL，p < 0.01），血浆FFA降低（423 +/- 42-317 +/- 40 μ mol/l，p < 0.05），尽管血浆脂联素增加更大（6.5 +/- 0.4-15.5 +/- 0.7 ug/mL，p < 0.001），HbA 1c降低幅度更大（8.7 +/- 0.5-7.4 +/-0.3%，p < 0.01）、FPG（159 +/- 16-120 +/- 10 mg/dL，p < 0.01）和HOMA-IR（6.6 +/- 0.8-4.4 +/- 0.4，p < 0.005）。结论：在T2 DM中，低剂量吡格列酮（15 mg/天）在体重没有显著变化的情况下增加15-epi-LXA 4和脂联素水平。吡格列酮剂量递增至30 mg/天与15-epi-LXA 4的相似增加相关，尽管血浆脂联素浓度增加更大。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
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.