Bagdade J D, Kelley D E, Henry R R, Eckel R H, Ritter M C
Department of Medicine, Rush Medical College, Chicago, Illinois, USA.
Diabetes. 1997 Mar;46(3):414-20. doi: 10.2337/diab.46.3.414.
Although the relationship between the actions of cholesteryl ester transfer protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have previously shown that CET is increased in IDDM patients receiving conventional subcutaneous insulin treatment and normalized when systemic insulin levels are lowered with intraperitoneal insulin delivery (IP). Since CET has been found by many observers to also be accelerated in NIDDM, we sought to determine whether the same salutary effect could be achieved in insulin-requiring NIDDM men before and 7 months after randomization to an intensive treatment regimen (Rx) of either IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7% post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P < 0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87 mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx), though an upward trend followed IP. Before randomization, CET estimated with both mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic control subjects (P < 0.001). With improved glycemic control, CE mass transfer declined in both groups, but only reached normal levels in the IP group (MDI group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post-Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/- 6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P < 0.005) in the subjects receiving MDI. Total lipolytic activity after intensive treatment was unchanged from pretreatment levels, which were similar to those of the reference group. Although directional changes in lipoprotein lipase (LpL) and hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and IP were observed, they were not statistically significant. Thus, while improved glycemic control alone achieved by either MDI or IP reduced the pathological increase in CET in these insulin-treated NIDDM men, normalization was only achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained abnormally increased in NIDDM patients treated rigorously with conventional subcutaneous insulin delivery.
尽管胆固醇酯转运蛋白（CETP）的作用与动脉粥样硬化之间的关系很复杂，但大量证据表明其活性（胆固醇酯转运[CET]）具有促动脉粥样硬化作用。我们之前已经表明，接受常规皮下胰岛素治疗的1型糖尿病（IDDM）患者的CET增加，而当通过腹膜内胰岛素输注（IP）降低全身胰岛素水平时，CET恢复正常。由于许多观察家发现2型糖尿病（NIDDM）患者的CET也会加速，我们试图确定在随机分配到IP（n = 9）或每日多次胰岛素注射（MDI；n = 13）强化治疗方案之前和之后7个月，需要胰岛素治疗的NIDDM男性患者是否能获得相同的有益效果。两组的糖化血红蛋白（HbA1c）改善程度相同（MDI组：治疗前9.4 +/- 1.1%，治疗后7.2 +/- 0.7%[P < 0.001]；IP组：治疗前9.2 +/- 1.3%，治疗后7.1 +/- 0.5%[P < 0.001]）。与治疗前水平相比，两种治疗方法均未使血浆甘油三酯发生显著变化（MDI组：治疗前136 +/- 80 mg/dl，治疗后139 +/- 87 mg/dl；IP组：治疗前157 +/- 63 mg/dl，治疗后188 +/- 89 mg/dl），不过IP治疗后甘油三酯有上升趋势。在随机分组前，通过质量法和同位素法评估的NIDDM患者的CET均高于非糖尿病对照受试者（P < 0.001）。随着血糖控制的改善，两组的胆固醇酯质量转移均下降，但仅IP组降至正常水平（MDI组2小时时：治疗前49.0 +/- 13.7[平均值 +/- 标准差]pg，治疗后29.5 +/- 15.3 microg[-39.7%，P < 0.01]；IP组2小时时：治疗前40.8 +/- 23.3 microg，治疗后10.9 +/- 6.5 microg[-73.2%，P < 0.05]），而接受MDI治疗的受试者的CET仍异常升高（P < 0.005）。强化治疗后的总脂解活性与治疗前水平相比无变化，治疗前水平与参考组相似。尽管观察到脂蛋白脂肪酶（LpL）和肝甘油三酯脂肪酶（HTGL）的变化方向与MDI和IP治疗后的IDDM患者相似，但差异无统计学意义。因此，虽然MDI或IP单独改善血糖控制都降低了这些接受胰岛素治疗的NIDDM男性患者CET的病理性升高，但只有IP治疗组恢复到正常水平。尽管HbA1c水平接近正常，但接受常规皮下胰岛素注射严格治疗的NIDDM患者的CET仍异常升高。
