torcetrapib 对 Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events（ILLUMINATE）试验中受试者的血糖、胰岛素和血红蛋白 A1c 的影响。

Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial.

机构信息

The Heart Research Institute, Sydney, Australia.

出版信息

Circulation. 2011 Aug 2;124(5):555-62. doi: 10.1161/CIRCULATIONAHA.111.018259. Epub 2011 Jul 18.

DOI:10.1161/CIRCULATIONAHA.111.018259

PMID:21804130

Abstract

BACKGROUND

High-density lipoproteins have antidiabetic properties in vitro. Furthermore, elevated high-density lipoprotein levels accompanying a genetic deficiency of cholesteryl ester transfer protein are associated with decreased levels of plasma glucose. We now investigate effects on glucose homeostasis of inhibiting cholesteryl ester transfer protein with torcetrapib.

METHODS AND RESULTS

A post hoc analysis of the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial was conducted to investigate effects of the cholesteryl ester transfer protein inhibitor torcetrapib on glycemic control in the 6661 diabetic patients in the trial. At baseline, there were no differences between the 2 treatment arms with respect to plasma glucose, insulin, hemoglobin A(1c), or the homeostasis model assessment of insulin resistance. After 3 months, the diabetic subjects taking the combination of torcetrapib plus atorvastatin had plasma glucose levels 0.34 mmol/L lower (P<0.0001) and insulin levels 11.7 μU/mL lower (P<0.0001) than in those receiving atorvastatin alone. Homeostasis model assessment of insulin resistance values decreased from 49.1 to 47.3 (P<0.0001) in the torcetrapib/atorvastatin arm compared with an increase in homeostasis model assessment of insulin resistance in the atorvastatin arm. At the 6-month time point, the mean hemoglobin A(1c) level in the atorvastatin arm was 7.29% compared with 7.06% in the torcetrapib/atorvastatin arm (P<0.0001). These effects of torcetrapib remained apparent for up to 12 months. Torcetrapib also lowered both glucose and insulin levels in the participants without diabetes mellitus, although the effects were not as great as in those with diabetes mellitus.

CONCLUSIONS

Treatment with torcetrapib improves glycemic control in atorvastatin-treated patients with type 2 diabetes mellitus. It remains to be determined whether this effect is the consequence of raising high-density lipoprotein.at

CLINICAL TRIAL REGISTRATION

http:www.clinicaltrials.gov. Unique identifier: NCT00134264.

摘要

背景

高密度脂蛋白在体外具有抗糖尿病作用。此外，伴随胆固醇酯转移蛋白遗传缺陷而升高的高密度脂蛋白水平与血浆葡萄糖水平降低有关。我们现在研究用 torcetrapib 抑制胆固醇酯转移蛋白对葡萄糖稳态的影响。

方法和结果

对脂质水平管理的调查以了解其对动脉粥样硬化事件的影响（ILLUMINATE）试验进行了事后分析，以研究胆固醇酯转移蛋白抑制剂 torcetrapib 对试验中 6661 例糖尿病患者血糖控制的影响。在基线时，两种治疗组之间在血浆葡萄糖、胰岛素、糖化血红蛋白或胰岛素抵抗的稳态模型评估方面没有差异。3 个月后，服用 torcetrapib 加阿托伐他汀的糖尿病患者的血浆葡萄糖水平低 0.34mmol/L（P<0.0001），胰岛素水平低 11.7μU/mL（P<0.0001），而单独服用阿托伐他汀的患者则无差异。与阿托伐他汀组相比，torcetrapib/阿托伐他汀组的胰岛素抵抗稳态模型评估值从 49.1 降至 47.3（P<0.0001）。在阿托伐他汀组，胰岛素抵抗的稳态模型评估值增加。在 6 个月时，阿托伐他汀组的平均糖化血红蛋白水平为 7.29%，而 torcetrapib/阿托伐他汀组为 7.06%（P<0.0001）。torcetrapib 的这些作用在长达 12 个月的时间内仍然明显。torcetrapib 还降低了无糖尿病参与者的血糖和胰岛素水平，尽管其作用不如糖尿病患者明显。