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.

Department of Metabolic Care and Gerontology University Hospital Charles University Sokolská 581 50005 Hradec Králové Czech Republic

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Use of ultra high performance liquid chromatography-tandem mass spectrometry to demonstrate decreased serum statin levels after extracorporeal LDL-cholesterol elimination