1型糖尿病无肾衰竭患者及非糖尿病对照受试者的脂质转运蛋白活性及其与冠状动脉钙化的关联。

Lipid transfer protein activities in type 1 diabetic patients without renal failure and nondiabetic control subjects and their association with coronary artery calcification.

作者信息

Colhoun H M, Scheek L M, Rubens M B, Van Gent T, Underwood S R, Fuller J H, Van Tol A

机构信息

Royal Free and University College London Medical School, UK.

出版信息

Diabetes. 2001 Mar;50(3):652-9. doi: 10.2337/diabetes.50.3.652.

DOI:10.2337/diabetes.50.3.652

PMID:11246887

Abstract

This study examined the role of cholesteryl ester transfer (CET), cholesteryl ester transfer protein (CETP) activity, and phospholipid transfer protein (PLTP) activity in the increased prevalence of coronary artery calcification (CAC) in diabetic subjects compared with nondiabetic subjects and in the loss of the sex difference in CAC in diabetes. CETP activity, PLTP activity, and CET were measured in 195 type 1 diabetic subjects without renal failure and 194 nondiabetic control subjects of similar age (30-55 years) and sex distribution (50% female). CAC was quantified with electron beam computed tomography. CETP activity was higher in diabetic subjects (mean 84 arbitrary units [AU]) than in nondiabetic subjects (80 AU, P = 0.028). PLTP activity was also higher in diabetic subjects (96 AU) than in nondiabetic subjects (81 AU, P < 0.001). However, CET was lower in diabetic men (geometric mean 32 nmol. ml(-1).h(-1)) than nondiabetic men (37 nmol.ml(-1).h(-1), P = 0.004) and did not differ between diabetic (30 nmol. ml(-1).h(-1)) and nondiabetic (32 nmol.ml(-1).h(-1), P = 0.3) women. CETP and PLTP activities were not associated with CAC. CET was positively associated with CAC in both diabetic and nondiabetic subjects (odds ratio per 10 nmol.ml(-1).h(-1) increase in CET in all subjects = 1.4, P = 0.001). The prevalence of CAC was similar in diabetic (51%) and nondiabetic (54%, P = 0.7) men but was much higher in diabetic (47%) than nondiabetic (21%, odds ratio 3.6, P < 0.001) women so that there was no sex difference in CAC in diabetic subjects. The odds of CAC in diabetic women compared with nondiabetic women was altered little by adjustment for CETP activity, PLTP activity, or CET (odds ratio on adjustment 3.7, P < 0.001). The greater effect of diabetes on CAC in women than in men, i.e., the loss of the sex difference in CAC, was independent of CETP and PLTP activity and CET. In conclusion, among both diabetic and nondiabetic subjects, higher cholesteryl ester transfer is a risk factor for CAC. However, abnormalities in cholesteryl ester transfer or lipid transfer protein activities do not underlie the increased CAC risk in diabetic women compared with nondiabetic women or the loss of the sex difference in CAC in diabetes.

摘要

本研究探讨了胆固醇酯转运（CET）、胆固醇酯转运蛋白（CETP）活性和磷脂转运蛋白（PLTP）活性在糖尿病患者冠状动脉钙化（CAC）患病率升高（与非糖尿病患者相比）以及糖尿病患者CAC性别差异消失中所起的作用。对195例无肾衰竭的1型糖尿病患者和194例年龄相仿（30 - 55岁）、性别分布相似（50%为女性）的非糖尿病对照者测定了CETP活性、PLTP活性和CET。采用电子束计算机断层扫描对CAC进行定量分析。糖尿病患者的CETP活性（平均84任意单位[AU]）高于非糖尿病患者（80 AU，P = 0.028）。糖尿病患者的PLTP活性（96 AU）也高于非糖尿病患者（81 AU，P < 0.001）。然而，糖尿病男性的CET较低（几何均值32 nmol·ml⁻¹·h⁻¹），低于非糖尿病男性（37 nmol·ml⁻¹·h⁻¹，P = 0.004），而糖尿病女性（30 nmol·ml⁻¹·h⁻¹）和非糖尿病女性（32 nmol·ml⁻¹·h⁻¹，P = 0.3）之间的CET无差异。CETP和PLTP活性与CAC无关。在糖尿病和非糖尿病患者中，CET均与CAC呈正相关（所有受试者中CET每增加10 nmol·ml⁻¹·h⁻¹的优势比 = 1.4，P = 0.001）。糖尿病男性（51%）和非糖尿病男性（54%，P = 0.7）的CAC患病率相似，但糖尿病女性（47%）的CAC患病率远高于非糖尿病女性（21%，优势比3.6，P < 0.001），因此糖尿病患者中不存在CAC的性别差异。调整CETP活性、PLTP活性或CET后，糖尿病女性与非糖尿病女性相比患CAC的几率变化不大（调整后的优势比为3.7，P < 0.001）。糖尿病对女性CAC的影响大于男性，即CAC性别差异的消失，与CETP和PLTP活性以及CET无关。总之，在糖尿病和非糖尿病患者中，较高的胆固醇酯转运是CAC的一个危险因素。然而，胆固醇酯转运或脂质转运蛋白活性异常并非糖尿病女性与非糖尿病女性相比CAC风险增加或糖尿病患者中CAC性别差异消失的原因。