Effects of Atorvastatin on LDL sub‐fractions and peroxidation in type 1 diabetic patients: a randomised double‐blind placebo‐controlled study (original) (raw)
Related papers
The effects of atorvastatin and rosuvastatin on oxidative stress in diabetic patients
European Journal of Internal Medicine, 2011
Aim: Diabetes is associated with abnormalities in lipid profile and increased oxidative stress. Statins are preferred agents in diabetic patients due to their antioxidant and LDL-C lowering effects. This study is designed to compare the effects of atorvastatin and rosuvastatin on low density lipoprotein cholesterol (LDL-C), lipid hydroperoxide (LOOH), total oxidant status (TOS) and total antioxidant capacity (TAC) in diabetic patients with hyperlipidemia. Materials and methods: Sixty two patients who have type 2 diabetes mellitus with serum LDL levels more than 100 mg/dL were randomly assigned to receive atorvastatin 20 mg (n = 31) or rosuvastatin 10 mg (n =31). Blood tests were performed at the beginning of the study and after three months. Results: There were no statistically significant differences in the pre-and after treatment levels of the LDL-C between groups. TAC values were increased in both groups and statistically significant in the former group (p = 0.007). There was no diferrence between the change percentages ((after treatment TAC − pretreatment TAC) / pretreatment level) of TAC between two treatment groups. The effects of two drugs on the other oxidative parameters were not significantly different. Conclusion: Both atorvastatin and rosuvastatin may be helpful in reducing increased oxidative stress in diabetic patients with hyperlipidemia.
Antioxidant Effect of Atorvastatin in Type 2 Diabetic Patients
Pharmacology & Pharmacy, 2010
Evidence has long been existed regarding the relationship between oxidative stress and diabetes. The present study was conducted to assess the effect of atorvastatin on selected oxidative stress parameters and its effect on lipid profile parameters in dyslipidaemic type 2 diabetic patients. Fifty nine dyslipidaemic type 2 diabetic patients were included in this study. A full history was taken and general examination was performed. The patients were taking an oral hypoglycaemic drug (glibenclamide) during the study. The patients were followed up for 60 days and divided randomly into 2 groups. Group I (n = 31) received no drug and served as dyslipidaemic diabetic control. Group II (n = 28) received atorvastatin tablets 20 mg once daily at night. Blood samples were drawn from the patients at the beginning and after 60 days of follow up between 8:30 and 10:30 am after at least 12-14 hours fasting. Fasting blood glucose, lipid profile, selective oxidative stress parameters, glutathione S reductase (GSH), malondialdehyde (MDA) levels, glutathione S transferase (GST) and catalase (CAT) activities were measured. Renal and hepatic functions were also assessed. The results showed that atorvastatin treatment produced significant increase in serum levels of GSH and High Density Lipoprotein (HDL), while serum levels of MDA, Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C) and Very Low Density Lipoprotein (VLDL) were significantly decreased. However, no significant effect was observed regarding CAT and GST activity. There were insignificant correlations between atorvastatin induced changes in the oxidation markers and the observed changes of the lipid profile. In conclusion, the antioxidant effect of atorvastatin could be unrelated to its hypolipidemic action as there was insignificant correlation between changes in lipid profile and oxidative stress in this study.
Atherosclerosis, 2004
Objective: To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment. Research Design and Methods: T1DM patients with high cholesterol received Atorvastatin 20 mg with either placebo (group AP, n = 11) or d-␣-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation at inclusion and after 3 and 6 months. Results: Serum cholesterol and triglycerides decreased to the same extent (29 and 21% respectively) in both groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE (P < 0.0001, between-group comparison by repeated measures ANOVA) but relative to lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in AP and did not change in AE (P = 0.02). The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE (P = 0.028). Plasma malondialdehyde decreased by 35% in both groups (P = 0.002) but not when adjusted for lipids. Conclusions: In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs. These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin.
Pharmacological Research, 2005
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 noncholesterol 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 (6.97 mol l −1 versus 5.11 mol l −1 , p = 0.012) and lower levels of sitosterol (5.03 mol l −1 versus 8.98 mol l −1 , p < 0.001) and campesterol (6.35 mol l −1 versus 9.80 mol 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 (4.11 mol l −1 versus 7.83 mol 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 log lathosterol 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.
Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities
Atherosclerosis, 2004
Low-density lipoprotein (LDL) cholesterol is an established risk factor for coronary heart disease (CHD). In the presence of oxidative stress LDL particles can become oxidized to form a lipoprotein species that is particularly atherogenic. Indeed, oxidized LDL (oxLDL) is pro-inflammatory, it can cause endothelial dysfunction and it readily accumulates within the arterial wall. Several factors may influence the susceptibility of LDL to oxidation, including its size and composition, and the presence of endogenous antioxidant compounds, such as ␣-tocopherol. Individuals with type 2 diabetes or the metabolic syndrome have high levels of oxidative stress and consequently are at an increased risk for cardiovascular events. Reducing oxidative stress has been proposed as a potential approach to prevent CHD and antioxidant vitamins have been employed with encouraging results in experimental models of atherosclerosis. However, clinical trials have not demonstrated consistent beneficial effects of antioxidants on cardiovascular outcomes. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the first-line choice for lowering total and LDL cholesterol levels and they have been proven to reduce the risk of CHD. Recent data suggest that these compounds, in addition to their lipid-lowering ability, can also reduce the production of reactive oxygen species and increase the resistance of LDL to oxidation. It may be that the ability of statins to limit the oxidation of LDL contributes to their effectiveness at preventing atherosclerotic disease. (R.S. Rosenson). may also be at increased risk of developing CHD. Indeed, although levels of LDL may not be elevated, its atherogenic potential may be increased by oxidative modification.
Atherosclerosis, 2000
Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10 − 80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of 52.6 mmol/l (100 mg/dl) maintained the same dosage regimen until they had completed 16 weeks of treatment. Patients not reaching the target LDL-C underwent dose titration to atorvastatin 20, 40 and 80 mg/day at Weeks 4, 8 and 12, respectively. All 88 patients who completed the study attained target LDL-C levels and 52 (59%) of patients achieved the target goal at the starting dose of atorvastatin 10 mg/day. In this group the differences between baseline and post-treatment values for LDL-C were 4.390.7 mmol/l (166 926 mg/dl) versus 2.2 90.4 mmol/l (87 914 mg/dl) (PB 0.0001), respectively, a decrease of 47%. Similar trends were observed for total cholesterol, triglycerides, very low-density lipoprotein cholesterol and apolipoprotein B levels. The safety profile of atorvastatin in these patients was highly favorable and similar to those reported with other statins. Only one patient withdrew due to a possible drug-related adverse event. These data confirm the marked efficacy and safety of atorvastatin in type 2 diabetic patients with hyperlipidemia and the efficacy of atorvastatin 10 mg in helping patients attain their LDL-C goal.
International Journal of Cardiology, 2005
Background: The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. Methods: Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy (n=33), or as replacement therapy (n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment.
ARYA atherosclerosis, 2017
The major aim of this study was evaluating the effect of atorvastatin treatment on thiobarbituric acid reactive substances (TBARS), ferric reducing the ability of plasma (FRAP), small dense low-density lipoprotein cholesterol (sdLDL) and lipid profile in coronary artery disease (CAD) patients. This study was carried out on 83 patients with angiographically proven coronary artery stenosis (52 men and 31 women) at Shahid Madani Hospital, Khorramabad, Iran, in 2015. The patients were divided into the 3 groups. 27 patients were classified statins consumption less than 6 days, 28 patients for 6 to 90 days, and 28 patients for more than 90 days. The level of sdLDL, lipid profile, TBARS and FRAP were assayed. FRAP levels of patients that received atorvastatin for more than 90 days (832 ± 101) were significantly elevated (P = 0.01) compared to the patients received atorvastatin less than 6 days (688 ± 75), whereas the levels of TBARS diminished significantly (P = 0.04). Also, the levels of ...
Molecular and cellular biochemistry, 2000
Atorvastatin is an established HMG-CoA reductase inhibitor which effectively reduces the plasma low density lipoprotein (LDL)-cholesterol level in hyperlipidemic patients. The present study was designed to investigate whether atorvastatin treatment can modify the biochemical content of oxidized LDL in hyperlipidemic patients and the ability of oxidized LDL to impair the endothelium-dependent relaxation of blood vessels. With atorvastatin (10 mg/day) treatment for 4 weeks in 19 type IIa hyperlipidemic patients, total cholesterol level was lowered by 23%, LDL-cholesterol was lowered by 32% and triacylglycerol was lowered by 19% as compared with dietary therapy alone. High density lipoprotein levels increased by approximately 9%. The ability of oxidized LDL from hyperlipidemic patients after atorvastatin treatment to impair the endothelium-dependent relaxation was significantly reduced as compared with dietary intervention alone. Analysis of the biochemical contents of oxidized LDL fro...