Ghazzi M N, Perez J E, Antonucci T K, Driscoll J H, Huang S M, Faja B W, Whitcomb R W
Parke-Davis Pharmaceutical Research, Diabetes and Metabolic Diseases, Ann Arbor, Michigan 48105, USA.
Diabetes. 1997 Mar;46(3):433-9. doi: 10.2337/diab.46.3.433.
Troglitazone is a thiazolidinedione under development for the treatment of NIDDM and potentially other insulin-resistant disease states. Treatment with troglitazone is associated with an improvement in hyperglycemia, hyperinsulinemia, and insulin-mediated glucose disposal. No significant side effects have been observed in humans. Because of reported cardiac changes in animals treated with drugs of this class, this multicenter 48-week study was conducted to evaluate whether NIDDM patients treated with troglitazone develop any cardiac mass increase or functional impairment. A total of 154 NIDDM patients were randomized to receive troglitazone 800 mg q.d. or glyburide titrated to achieve glycemic control (< or =20 mg b.i.d. or q.d.). Two-dimensional echocardiography and pulsed Doppler were used to measure left ventricular mass index (LVMI), cardiac index (CI), and stroke volume index (SVI). All echocardiograms were performed at each center (baseline, 12, 24, 36, and 48 weeks), recorded on videotape, and forwarded to a blinded central echocardiographic interpreter for analysis. The results showed that LVMI of patients treated with troglitazone was not statistically or clinically different from baseline after 24 or 48 weeks. Statistically significant increases in SVI and CI and a statistically significant decrease in diastolic pressure and estimated peripheral resistance were observed in troglitazone-treated patients. These results were not sex-specific. Glycemic benefits of troglitazone treatment were observed as evidenced by long-term improvement of HbA1c and C-peptide levels. Furthermore, triglycerides were significantly lower, and HDL was significantly higher at weeks 24 and 48. In conclusion, NIDDM patients treated with troglitazone do not show any cardiac mass increase or cardiac function impairment. Conversely, patients on troglitazone benefited from enhanced cardiac output and stroke volume, possibly as a result of decreased peripheral resistance. Treatment with troglitazone appears to have a favorable impact on known cardiovascular risk factors and could potentially lower cardiovascular morbidity in NIDDM patients.
曲格列酮是一种正在研发用于治疗非胰岛素依赖型糖尿病（NIDDM）以及可能的其他胰岛素抵抗疾病状态的噻唑烷二酮类药物。使用曲格列酮治疗可改善高血糖、高胰岛素血症以及胰岛素介导的葡萄糖代谢。在人体中未观察到明显的副作用。由于有报道称使用此类药物治疗的动物出现了心脏变化，因此开展了这项为期48周的多中心研究，以评估接受曲格列酮治疗的NIDDM患者是否会出现任何心脏质量增加或功能损害。总共154例NIDDM患者被随机分组，分别接受每日800毫克曲格列酮治疗或格列本脲治疗，后者通过滴定来实现血糖控制（每日两次或每日一次，每次剂量≤20毫克）。使用二维超声心动图和脉冲多普勒来测量左心室质量指数（LVMI）、心脏指数（CI）和每搏输出量指数（SVI）。所有超声心动图检查均在各中心进行（基线、第12、24、36和48周），记录在录像带上，并转发给一位不知情的中央超声心动图解读员进行分析。结果显示，接受曲格列酮治疗的患者在24周或48周后，其LVMI与基线相比在统计学上和临床上均无差异。在接受曲格列酮治疗的患者中观察到SVI和CI有统计学意义的增加，舒张压和估计外周阻力有统计学意义的降低。这些结果无性别差异。曲格列酮治疗带来的血糖益处可通过糖化血红蛋白（HbA1c）和C肽水平的长期改善得到证明。此外，在第24周和第48周时，甘油三酯显著降低，高密度脂蛋白（HDL）显著升高。总之，接受曲格列酮治疗的NIDDM患者未出现任何心脏质量增加或心脏功能损害。相反，使用曲格列酮治疗的患者受益于心脏输出量和每搏输出量的增加，这可能是外周阻力降低的结果。曲格列酮治疗似乎对已知的心血管危险因素有有利影响，并可能降低NIDDM患者的心血管发病率。
