Free fatty acid kinetics during long-term treatment with pioglitazone added to sulfonylurea or metformin in Type 2 diabetes
Free fatty acid kinetics during long-term treatment with pioglitazone added to sulfonylurea or metformin in Type 2 diabetes
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DOI：
10.1111/j.1365-2796.2008.02040.x
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发表时间：
2009-04-01
影响因子：
11.1
通讯作者：
Pacini, G.
中科院分区：
文献类型：
--
作者：
Roden, M.;Mariz, S.;Pacini, G.
游离脂肪酸（FFA）与胰岛素作用受损有关，但其在糖尿病治疗期间介导长期胰岛素增敏中的作用尚不清楚。为了检查吡格列酮加用现有治疗对FFA动力学和胰岛素作用的影响。两项为期2年的随机、平行组、双盲、双模拟临床试验。欧洲171个中心，澳大利亚和加拿大。二甲双胍或磺脲类药物治疗效果不佳的2型糖尿病男性和女性患者。患者随机接受吡格列酮治疗（15-45 mg/天（-1）; n = 319）或二甲双胍（850-2550 mg/天（-1）; n = 320）作为格列齐特或吡格列酮（n = 317）的辅助治疗，对比格列齐特（80-320 mg/d（-1）; n = 313）作为二甲双胍的附加治疗。在选定的中心治疗前和治疗期间口服葡萄糖耐量试验期间的血浆FFA曲线（n = 588）。在第104周，与磺脲类药物+二甲双胍组相比，吡格列酮联合磺脲类药物治疗使空腹FFA降低0.08 mmol L（-1），联合二甲双胍治疗使空腹FFA降低0.11 mmol L（-1（0.03 mmol L（-1），P = 0.05和0.04 mmol L（-1），P < 0.05），并且这伴随着空腹脂肪组织胰岛素敏感性的显著改善。两组间攻毒后FFA的变化相似，与肝脏转氨酶、胰岛素作用和分泌的变化无关。FFA对胰岛素敏感性受治疗（P < 0.001）和访视（P < 0.05）的影响。吡格列酮联合磺脲类药物治疗后FFA胰岛素敏感性升高（P < 0.05），格列齐特联合二甲双胍治疗后FFA胰岛素敏感性降低（P < 0.05），吡格列酮长期改善脂肪组织胰岛素敏感性和降低空腹FFA有助于减轻2型糖尿病的脂毒性。
Free fatty acids (FFAs) are linked to impaired insulin action, but their role in mediating long-term insulin sensitization during diabetes treatment is unclear.To examine the effect of pioglitazone addition to existing therapy on FFA dynamics and insulin action.Two 2-year, randomized, parallel-group, double-blind, double-dummy, clinical trials.One hundred and seventy-one centres in Europe, Australia and Canada.Male and female patients with Type 2 diabetes inadequately managed with metformin or sulfonylurea.Patients were randomized to pioglitazone (15-45 mg day(-1); n = 319) or metformin (850-2550 mg day(-1); n = 320) as add-on therapy to gliclazide or pioglitazone (n = 317) versus gliclazide (80-320 mg day(-1); n = 313) as add-on therapy to metformin.Plasma FFA profiles during oral glucose tolerance tests in selected centres before and during treatment (n = 588).At Week 104, pioglitazone treatment decreased fasting FFAs by 0.08 mmol L(-1) when added to sulfonylurea and by 0.11 mmol L(-1) when added to metformin versus the respective sulfonylurea + metformin groups (0.03 mmol L(-1), P = 0.05 and 0.04 mmol L(-1), P < 0.05), and this was accompanied by significant improvements in fasting adipose tissue insulin sensitivity. Changes in postchallenge FFAs were similar between groups and not related to changes in liver transaminases, insulin action and secretion. However, the sensitivity of FFA to insulin was affected by treatment (P < 0.001) and visit (P < 0.05). Insulin sensitivity of FFA rose when pioglitazone was added to sulfonylurea (P < 0.05), but decreased for gliclazide + metformin (P < 0.05).Long-term improvements in adipose tissue insulin sensitivity and reduction in fasting FFAs with pioglitazone may help to reduce lipotoxicity in Type 2 diabetes.