Smahelová Alena, Hyspler Radek, Haas Tomás, Tichá Alena, Bláha Vladimír, Zadák Zdenĕk
Department of Metabolic Care and Gerontology, University Hospital, Charles University, Sokolská 581, 50005 Hradec Králové, Czech Republic.
Pharmacol Res. 2005 Jan;51(1):31-6. doi: 10.1016/j.phrs.2004.07.007.
An increased risk of cardiovascular morbidity and mortality in diabetes mellitus type 2 has been associated with disturbances of lipid homeostasis. Recently, decreased intestinal absorption of cholesterol and increased liver cholesterol production have been reported. To investigate the influence of cholesterol lowering therapy using statin on cholesterol turnover in diabetes mellitus type 2, the levels of non-cholesterol based sterols were studied. One hundred and thirty five patients with type 2 diabetes and non-diabetic controls with cardiovascular diseases were studied. Both groups were divided into two subgroups: treated with atorvastatin and without statin therapy. The diabetics showed significantly higher levels of lathosterol (6.97micromol l(-1) versus 5.11micromol l(-1), p = 0.012) and lower levels of sitosterol (5.03micromol l(-1) versus 8.98micromol l(-1), p < 0.001) and campesterol (6.35micromol l(-1) versus 9.80micromol l(-1), p < 0.001). Non-diabetics showed no significant differences in non-cholesterol based sterols in relation to atorvastatin therapy. A significantly lower level of lathosterol as well as a decrease in lathosterol/cholesterol ratio in the statin treated groups was found in diabetics (4.11micromol l(-1) versus 7.83micromol l(-1), p < 0.001). The results based on ANOVA analysis show that the effect of atorvastatin on the lathosterol level is more pronounced in diabetics. Regression analysis showed the relationship between increased triglycerides levels and the increase in cholesterol synthesis. The calculated regression model for loglathosterol in diabetics has the following form: log(lathosterol) = 2.76 - 0.52.statin + 0.22.cholesterol (ANOVA, p < 0.001, R(2) = 34%, p = 0.005 for statin, p < 0.001 for cholesterol). We conclude that in spite the total cholesterol level in diabetics type 2 is not increased, its endogenous synthesis is enhanced. Our results show that the diabetics type 2 with increased serum lathosterol and expressed metabolic syndrome (mild increase of triglycerides) might represent a suitable group for intensive treatment with statins.
2型糖尿病患者心血管疾病发病率和死亡率增加与脂质稳态紊乱有关。最近，有报道称肠道胆固醇吸收减少和肝脏胆固醇生成增加。为了研究使用他汀类药物降低胆固醇治疗对2型糖尿病患者胆固醇周转的影响，对非胆固醇类甾醇水平进行了研究。研究了135例2型糖尿病患者和患有心血管疾病的非糖尿病对照者。两组均分为两个亚组：接受阿托伐他汀治疗组和未接受他汀类药物治疗组。糖尿病患者的羊毛甾醇水平显著更高（6.97微摩尔/升对5.11微摩尔/升，p = 0.012），而植物甾醇水平更低（5.03微摩尔/升对8.98微摩尔/升，p < 0.001），菜油甾醇水平也更低（6.35微摩尔/升对9.80微摩尔/升，p < 0.001）。非糖尿病患者在阿托伐他汀治疗方面，非胆固醇类甾醇无显著差异。在糖尿病患者中，他汀治疗组的羊毛甾醇水平显著降低，且羊毛甾醇/胆固醇比值也降低（4.11微摩尔/升对7.83微摩尔/升，p < 0.001）。基于方差分析的结果表明，阿托伐他汀对羊毛甾醇水平的影响在糖尿病患者中更为显著。回归分析显示甘油三酯水平升高与胆固醇合成增加之间的关系。计算得出的糖尿病患者log羊毛甾醇的回归模型如下：log（羊毛甾醇）= 2.76 - 0.52.他汀 + 0.22.胆固醇（方差分析，p < 0.001，R² = 34%，他汀的p = 0.005，胆固醇的p < 0.001）。我们得出结论，尽管2型糖尿病患者的总胆固醇水平没有升高，但其内源性合成增强。我们的结果表明，血清羊毛甾醇升高且表现出代谢综合征（甘油三酯轻度升高）的2型糖尿病患者可能是他汀类药物强化治疗的合适人群。
