Bavirti Surekha, Ghanaat Farhad, Tayek John A
David Geffen School of Medicine at UCLA, Harbor-UCLA, Medical Center, Torrance, California 90509, USA.
Endocr Pract. 2003 Nov-Dec;9(6):487-93. doi: 10.4158/EP.9.6.487.
To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size.
We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically.
Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3).
This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.
确定曲格列酮在不依赖糖尿病控制的情况下是否会增加低密度脂蛋白（LDL）颗粒大小。
我们对10例2型糖尿病患者每日给予600 mg曲格列酮（一种过氧化物酶体增殖物激活受体γ激动剂），持续8周（其中8例完成研究）。然后停用曲格列酮治疗，使用其他控制糖尿病的药物再治疗4周。在第0、4、8和12周测定LDL、极低密度脂蛋白（VLDL）和高密度脂蛋白（HDL）的浓度及亚群，以及血糖和糖化血红蛋白（HbA1c），并进行统计学分析。
小而密的LDL胆固醇在糖尿病患者中常见，被认为与冠状动脉疾病风险增加有关。曲格列酮治疗4周和8周后，糖尿病控制均显著改善（基线、第4周和第8周的平均HbA1c值分别为8.0±0.7%、7.4±0.5%和7.0±0.7%；P<0.05）。停用曲格列酮治疗4周后，HbA1c（12周时为6.5±0.6%）和血糖水平（8周时为126±19 mg/dL，12周时为145±9 mg/dL）无显著差异。曲格列酮治疗在第4周和第8周增加了大LDL颗粒，这一变化显著（P<0.05）增大了LDL颗粒大小（基线、第4周和第8周分别为20.5±0.3 nm、21.2±0.3 nm和21.3±0.2 nm）。曲格列酮治疗8周后，VLDL甘油三酯降低（195±37 mg/dL对136±28 mg/dL；P<0.05），HDL升高（31.6±2.4 mg/dL对35.5±2.9 mg/dL；P<0.05）。HDL值升高是由于小HDL颗粒增加。较大的VLDL颗粒（V5和V6）减少导致平均VLDL颗粒大小减小（59±3 nm对46±2 nm；P<0.05）。尽管停用曲格列酮治疗后糖尿病控制仍显著改善，但LDL颗粒大小降至基线值。这一变化是由于大LDL胆固醇颗粒（L3）减少。
本研究表明，曲格列酮治疗可增加LDL颗粒大小，减小VLDL颗粒大小，并增加小HDL颗粒。这些变化可能降低冠状动脉疾病风险。
