van der Meer Rutger W, Rijzewijk Luuk J, de Jong Hugo W A M, Lamb Hildo J, Lubberink Mark, Romijn Johannes A, Bax Jeroen J, de Roos Albert, Kamp Otto, Paulus Walter J, Heine Robert J, Lammertsma Adriaan A, Smit Johannes W A, Diamant Michaela
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Circulation. 2009 Apr 21;119(15):2069-77. doi: 10.1161/CIRCULATIONAHA.108.803916. Epub 2009 Apr 6.
Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients.
Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [(18)F]-2-fluoro-2-deoxy-D-glucose and [(11)C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content (P<0.001).
In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolism.
心脏病是2型糖尿病(T2DM)患者死亡的主要原因。吡格列酮已被证明与改善心脏结局有关,但同时也与心力衰竭风险升高有关。我们确定了吡格列酮对T2DM患者心肌功能的影响,及其与心脏高能磷酸、葡萄糖、脂肪酸代谢和甘油三酯含量的关系。
通过多巴酚丁胺负荷超声心动图评估,78名无结构性心脏病或可诱导性心肌缺血的T2DM男性患者被随机分为吡格列酮组(30mg/d)或二甲双胍组(2000mg/d),并分别给予匹配的安慰剂,治疗24周。主要终点是相对于心肌代谢变化,心脏舒张功能从基线开始的变化,通过磁共振成像、质子和磷磁共振波谱以及[(18)F]-2-氟-2-脱氧-D-葡萄糖和[(11)C]棕榈酸正电子发射断层扫描进行测量。没有患者发生心力衰竭。两种治疗方法在改善血糖控制、全身胰岛素敏感性和血压方面效果相似。吡格列酮组与二甲双胍组相比,早期峰值流速得到改善(P = 0.047),左心室顺应性提高。吡格列酮组与二甲双胍组相比,心肌葡萄糖摄取增加(P < 0.001),但吡格列酮相关的舒张功能改善与心肌底物代谢变化无关。二甲双胍不影响心肌功能,但相对于吡格列酮组,心脏做功减少(P = 0.006),这种变化与心肌葡萄糖摄取和脂肪酸氧化减少平行。两种治疗均未影响心脏高能磷酸代谢或甘油三酯含量。只有吡格列酮降低了肝脏甘油三酯含量(P < 0.001)。
在T2DM患者中,吡格列酮与左心室舒张功能的某些指标、心肌葡萄糖摄取和全身胰岛素敏感性的改善有关。然而,这些功能变化与心肌底物和高能磷酸代谢无关。