普伐他汀是否会增加2型糖尿病绝经后女性的乳糜微粒残粒分解代谢？

Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

作者信息

Ng T W K, Watts G F, Stuckey B G A, Ching H L, Chan D C F, Uchida Y, Sakai N, Yamashita S, Martins I J, Redgrave T G, Barrett P H R

机构信息

School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth, Australia.

出版信息

Clin Endocrinol (Oxf). 2005 Dec;63(6):650-6. doi: 10.1111/j.1365-2265.2005.02396.x.

DOI:10.1111/j.1365-2265.2005.02396.x

PMID:16343099

Abstract

OBJECTIVE

We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus.

PATIENTS AND MEASUREMENTS

Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism.

RESULTS

Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements.

CONCLUSIONS

In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.

摘要

目的

我们采用13C稳定同位素呼气试验以及检测血浆载脂蛋白（apo）B - 48和残粒样颗粒（RLP）-胆固醇，研究了普伐他汀对绝经后2型糖尿病女性乳糜微粒残粒分解代谢的影响。

患者与测量指标

19名绝经后2型糖尿病女性被随机分为两组，一组每天服用40mg普伐他汀，另一组不接受治疗，为期6周，随后有2周的洗脱期，之后两组交叉再进行6周的治疗。采用同位素比率质谱法和多室模型，根据呼出气体和血浆中13CO2的富集情况，测定乳糜微粒残粒样乳剂的分解代谢率（FCR）。还测量了血浆apo B - 48和RLP -胆固醇浓度，作为乳糜微粒残粒代谢的静态指标。

结果

普伐他汀显著降低了血浆胆固醇浓度（5.9±0.3 vs. 4.8±0.2 mmol/l；P<0.001）、低密度脂蛋白（LDL）-胆固醇（3.5±0.2 vs. 2.6±0.2 mmol/l；P<0.001）、甘油三酯（2.1±0.3 vs. 1.7±0.2 mmol/l；P = 0.017）、非高密度脂蛋白（HDL）-胆固醇（4.4±0.3 vs. 3.3±0.2 mmol/l；P<0.001）、羊毛甾醇/总胆固醇比值（2.6±0.2 vs. 2.0±0.3，P = 0.035）、apo B - 100（1.1±0.1 vs. 0.8±0.1 g/l；P = 0.001）、apo B - 48（4.8±0.9 vs. 3.3±0.6 mg/l；P = 0.016）以及RLP -胆固醇（31.4±8.2 vs. 18.6±4.6 mg/dl；P = 0.024）。普伐他汀还与谷甾醇/总胆固醇比值升高有关（2.8±0.3 vs. 3.1±0.3，P = 0.029）。然而，通过呼气或血浆清除率测量评估，普伐他汀并未显著改变乳糜微粒残粒样乳剂的分解代谢。