Home About us Contact
|
Home About us Contact | ||
|
|
||
LDL-C
Terms modified by LDL-C Selected AbstractsA double-blind, placebo-controlled trial of rosiglitazone for clozapine-induced glucose metabolism impairment in patients with SchizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009D. C. Henderson Objective:, The primary purpose of this 8-week double-blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated subjects with schizophrenia with insulin resistance. Method:, Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results:, Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non-significant improvement in SG (0.016 ± 0.006,0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8,7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low-density lipoprotein cholesterol (LDL-C) particle number (987 ± 443,694 ± 415, effect size = 0.30, P = 0.04). Conclusion:, Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine. [source] Interpreting clinical trials of diabetic dyslipidaemia: new insightsDIABETES OBESITY & METABOLISM, Issue 3 2009A. S. Wierzbicki Current treatment guidelines highlight the importance of aggressive lipid-modifying therapy in reducing cardiovascular risk in patients with type 2 diabetes. Statins are established as the cornerstone of dyslipidaemia management in diabetic patients, based on their efficacy in lowering levels of low-density lipoprotein cholesterol (LDL-C). However, statins fail to address the high residual cardiovascular risk in treated patients, some of which may be attributable to low HDL cholesterol (HDL-C) and elevated triglycerides and to a preponderance of small, dense LDL particles, indicating the need for further intervention. Fibrates are effective against all components of atherogenic dyslipidaemia associated with type 2 diabetes. Clinical studies, most notably the Fenofibrate Intervention and Event Lowering in Diabetes, indicate that fibrates, most likely in combination with a statin, have a secondary role in reducing cardiovascular risk in patients with type 2 diabetes, particularly in those without prior cardiovascular disease or patients with low HDL-C. Results are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes trial to fully evaluate the outcome benefits of this combination strategy. [source] Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patientsDIABETES OBESITY & METABOLISM, Issue 1 2005L. M. Gaudiani Aim:, In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD-treated T2DM patients. Methods:, This was a randomized, double-blind, parallel group, multicentre study in T2DM patients, 30,75 years of age, who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l (100 mg/dl) prior to study entry. Other antidiabetic medications were also allowed. Following 6 weeks of open-label simvastatin 20 mg/day, patients were randomized to the addition of either blinded ezetimibe 10 mg/day (n = 104) or an additional blinded simvastatin 20 mg/day (total simvastatin 40 mg/day; n = 110) for 24 weeks. Patients were stratified according to TZD type and dose (pioglitazone 15,30 vs. 45 mg/day; rosiglitazone 2,4 vs. 8 mg/day). Results:, LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (,20.8%) than by doubling the dose of simvastatin to 40 mg (,0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated. Conclusions:, Co-administration of ezetimibe with simvastatin, a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption, is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs. [source] Lipid-lowering therapy in patients with type 2 diabetes: the case for early interventionDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2008Armin Steinmetz Abstract Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy. Copyright © 2008 John Wiley & Sons, Ltd. [source] Plasma triglycerides and LDL cholesterol are related in a parabolic fashion in the general population and patients with Type 2 diabetes mellitus: long-term follow-up results from the Hoorn studyDIABETIC MEDICINE, Issue 9 2008M. C. G. J. Brouwers Abstract Aims Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation between plasma triglycerides and LDL-C, as previously demonstrated in familial combined hyperlipidaemia (FCHL), might account for this phenomenon. Methods Our hypothesis was tested in 1343 subjects derived from the general population who were studied on two occasions 6 years apart (the Hoorn study). Three groups were constructed depending on plasma triglycerides: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5 mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was ascertained by an oral glucose tolerance test. Results In a mixed linear model, a significant, positive relation between triglycerides and LDL-C was observed for males in group A (,a = 0.5, P < 0.001) and group B (,b = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (,c = ,0.2, P = 0.003). The regression slopes did not differ between diabetic and non-diabetic subjects. Similar results were obtained for women, with the exception that the relation was not significantly negative in group C (,c = ,0.1, P = 0.4). Conclusion Plasma triglcyerides and LDL-C are related in a parabolic fashion, not only in FCHL, but also in the general population and Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the effects of treatment that are frequently observed in hypertriglyceridaemic states. [source] Growth and Lipid Metabolism in Girls and Young Women with Epilepsy during Pubertal MaturationEPILEPSIA, Issue 7 2005Kirsi Mikkonen Summary:,Purpose: To assess growth and the serum lipid profile in girls with epilepsy receiving monotherapy at a mean age of 12.6 years and approximately 6 years later. Methods: A population-based cohort of 77 girls with epilepsy and 49 healthy controls participated in this follow-up study including two cross-sectional evaluations (age range, 8,18.5 years on the first evaluation, and 12.5,25.8 years on the second evaluation). Forty of the patients were initially taking valproate (VPA), 19, carbamazepine (CBZ), and 18, oxcarbazepine (OXC). Growth data were compiled, body mass index (BMI) was calculated, and serum total (TC), and high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol and triglyceride concentrations were analyzed. Results: Linear growth and final height did not differ between the patients and the controls. At follow-up, the mean BMI of the patients who were off medication (61%) was similar to that of the controls, whereas the patients initially treated with VPA who were still taking any medication had a higher BMI. On the first evaluation, the patients taking VPA had low serum HDL-C, and those taking CBZ or OXC had high serum TC and LDL-C concentrations. At follow-up, serum lipid levels were similar in the patients off medication and the controls. Conclusions: Neither epilepsy nor antiepileptic therapy affects linear growth or final height, but they may have unfavorable effects on body weight and serum lipid concentrations. Lipid-profile impairment seems to be transient if the medication is discontinued. Overweight is common in patients treated with VPA during puberty if epilepsy and medication continue into adulthood. [source] Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2010J. T. Real Eur J Clin Invest 2010; 40 (2): 89,94 Abstract Background, Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. Materials and methods, Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear cells. Results, Familial hypercholesterolaemia patients showed a significantly higher NF-kB (75·0 ± 20·7 vs. 42·7 ± 16·8 relative luminiscence units) and XO (0·44 ± 0·13 vs. 0·32 ± 0·09 mU mL,1) activities than controls. In addition, interleukin-1, interleukin-6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL-ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL-cholesterol (LDL-C), apolipoprotein B (apoB), NF-kB and hsCPR, and NF-kB activity was significantly associated with XO, hsCPR, LDL-ox, LDL-C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF-kB, and NF-kB activity in circulating mononuclear cells was independently associated with apoB and LDL-ox plasma values. Conclusion, Familial hypercholesterolaemia patients show increased activities of NF-kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF-kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients. [source] New Beverage for Cardiovascular Health, Proposal Based on Oriental and Occidental Food Culture from a World-Wide Epidemiological StudyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2008Emilio Hideyuki Moriguchi Objectives: To investigate whether combined isoflavones and antioxidants in oriental and occidental drinks reduce the risk of cardiovascular disease (CVD) in high-risk Japanese immigrants living in Brazil. Materials and methods: From among over 100 Japanese immigrants thirty-seven females aged 45,60 years in Porto Alegre, Brazil, were randomized after informed consent into two groups to drink 200 ml of whole soy cell juice (S) containing 7.5 g soy protein and 10 mg of isoflavones (aglycone) in peach juice or placebo peach juice (P) with 80 Kcal for 12 weeks. Health survey including 24-hour urine (24 U) examination were carried out before the randomization and after the double blind placebo controlled intervention study. Results: Both weight and body mass index (BMI) were significantly (p < 0.05, 0.01) decreased from the baseline only in the S group. Systolic blood pressure (SBP) was decreased significantly (p < 0.05) from the baseline in the S group with elevated 24 U isoflavone excretion (>10 µmol), and there was a significant (p < 0.05) inter-group difference between the S and P groups after intervention. Total and low density lipoprotein (LDL)-cholesterol (C) decreased significantly (p < 0.05) in the S group from the baseline and there was a significant difference (p < 0.05) between the S and P groups after intervention. HbA1c and atherogenic index (non-high density lipoprotein (HDL)-C/HDL-C) were significantly (p < 0.05) decreased in both groups. Conclusions: Soy isoflavones combined with fruit antioxidants, the combination of which might potentiate local nitric oxide (NO) affect, decreased SBP, total cholesterol and LDL-C. Peach juice itself improved blood glucose levels and the atherogenic index of the high-risk Japanese population in Brazil. [source] Treatment of hepatitis C virus with peg-interferon and ribavirin combination therapy significantly affects lipid metabolismHEPATOLOGY RESEARCH, Issue 2 2009Shinichiro Tada Aim:, We investigated lipid metabolism in patients with chronic hepatitis C virus (HCV), serotype 1, undergoing combination therapy with PEG-IFN ,-2b (PEG-IFN) and ribavirin (RBV). Methods:, A total of 185 patients with chronic HCV (HCV serotype 1; HCV RNA levels , 100 KIU/mL) who received a combination of PEG-IFN and RBV were enrolled. Results:, Sustained virological response (SVR) was obtained in 82 cases (44.3%). The median age, red blood cell and platelet counts differed significantly between the SVR and non-SVR groups before treatment. However there was no significant difference between total cholesterol (TC), LDL-cholesterol (LDL-C) and triglyceride (TG) levels before treatment. TC and LDL-C levels decreased during the treatment in both groups. In the SVR group, TC and LDL-C levels increased quickly after the end of the treatment and were higher than those before treatment. On the other hand, TC and LDL-C levels returned to pretreatment levels in the non-SVR group and were significantly lower than in the SVR group. TG levels were elevated in both groups after the beginning of treatment. After the end of treatment, this elevation persisted in the SVR group, while TG levels returned to pre-treatment levels in the non-SVR group. There was a significant difference in TG levels at 24 weeks after the end of the treatment between the 2 groups. In the non-SVR group some patients achieved normalization of ALT (alanine aminotransferase) but persistence of normal ALT levels did not contribute to the increase of TC and TG. Conclusion:, TC, LDL-C and TG levels increase only in patients with HCV, serotype 1, undergoing combination therapy when a SVR is achieved. [source] Increased serum lipids are associated with higher CD4 lymphocyte count in HIV-infected womenHIV MEDICINE, Issue 7 2006M Floris-Moore Objective Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. Methods A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. Results A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count,500 cells/,L had total cholesterol 41.8 mg/dL (P=0.002) and LDL-C 28.8 mg/dL (P=0.01) higher, on average, than women with a CD4 count <200 cells/,L. Women with a CD4 count of 200,499 cells/,L had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/,L (P=0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P=0.12). A higher CD4 count was also associated with higher apo B (P<0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. Conclusions Higher CD4 lymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population. [source] Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 yearsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008C. A. Dujovne Summary Aims:, This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE). Methods:, Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3,5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months. Results:, The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of , 3-fold consecutive elevations of liver transaminases (0.7%) or , 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of ,18% were maintained throughout the study. Conclusions:, Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction. [source] Insulin resistance phenotypes and coronary artery disease in a native Pakistani cohortINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2008A. S. Wierzbicki Summary Objective:, To determine the relationship between insulin resistance (IR) and atheroma burden in Pakistanis. Methods:, A prospective case,control study of 400 patients selected for the presence/absence of angiographic disease. Coronary atheroma burden was quantified and IR and cardiovascular risk factors were measured. Results:, The patients were divided into two groups by QuickI score. Waist circumference (90 ± 10 vs. 90 ± 9 cm; p = 0.7) was similar but the groups differed in body mass index (26.5 ± 3.7 vs. 24.2 ± 3.5 kg/m2; p < 0.001) and waist:hip ratio (0.94 ± 0.09 vs. 0.90 ± 0.06; p < 0.001). Lipid parameters showed similar high-density lipoprotein cholesterol (HDL-C) (0.77 ± 0.23 vs. 0.82 ± 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08,3.98) vs. 1.12 (0.37,3.61) mmol/l; p = 0.01], but no difference in low-density lipoprotein cholesterol (LDL-C) (2.75 ± 1.00 vs. 2.90 ± 0.94 mmol/l; p = 0.14). In insulin-resistant patients C-reactive protein (CRP) [6.8 (0.3,175.1) vs. 3.9 (0.2,57.9) mg/l: p < 0.001], sialic acid (82 ± 14 vs. 77 ± 15 mg/l; p < 0.001) aspartate transaminase [24 (7,171) vs. 21 (7,83) IU/l; p < 0.001] and gamma-glutamyl transferase [27 (8,482) vs. 21 (7,168) IU/l; p = 0.005] levels were increased. In insulin-resistant patients (n = 187), coronary artery disease (CAD) burden correlated (r = 0.55) with age (, = 1.62; p < 0.001), HDL-C (, = ,53.2; p < 0.001), lipoprotein (a) (, = 11.4; p = 0.007), smoking (, = 7.98; p = 0.004), CRP (, = 6.06; p = 0.03) and QuickI index (, = ,146; p = 0.04). In contrast in insulin-sensitive patients (n = 178) CAD burden (r = 0.46) correlated with LDL-C (, = 10.0; p = 0.02), CRP (, = 7.13; p = 0.03), HDL-C (, = ,38.1; p = 0.03), and weakly with age (, = 0.73; p = 0.07) and smoking (, = 5.52; p = 0.09). Conclusions:, Indian Asians show a dichotomous insulin-resistance phenotype. Atheroma is associated with low HDL-C and inflammation associated in all but LDL-C is a factor in the insulin sensitive in contrast to age and extent of IR in the insulin resistant. [source] The collaborative atorvastatin diabetes study: preliminary results,INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2005Olwen Glynn Owen Summary The Collaborative AtoRvastatin Diabetes Study (CARDS) is the first large primary prevention study to focus specifically on the role of a statin in patients aged 40,75 years with type 2 diabetes, but no signs or symptoms of pre-existing vascular disease and who had only average or below average cholesterol levels. The trial was a prospective double-blind randomised trial with 2383 type 2 diabetic subjects randomised to either 10-mg atorvastatin daily or placebo. Originally designed to run for 5 years, the trial was terminated over a year early in June 2003 on account of a clear benefit demonstrated for the intervention group. Over half of patients had a low-density lipoprotein cholesterol (LDL-C) below 3.3 mmol/l at entry and a quarter had an LDL-C <2.6 mmol/l. Atorvastatin 10 mg reduced LDL-C by 40% (1.2 mmol/l) on average. Results at 4 years showed a 37% relative risk reduction (p < 0.001) for atorvastatin 10 mg in the primary endpoint (acute coronary heart disease death, fatal or non-fatal myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, coronary revascularisation procedures and stroke). Among the secondary endpoints, total mortality was reduced by 27% (p = 0.05), acute coronary events by 36%, coronary revascularisation by 31% and stroke by 48%. The same magnitude of benefit was observed among patients with LDL-C above or below 3 mmol/l. Results observed were against a background where 9% of placebo patients had been permitted to start statin therapy after enrolment and 15% of patients on active treatment had discontinued atorvastatin. The true benefit of the intervention is therefore probably around 25% greater than the intention to treat analysis reports. [source] Improving lipid management , to titrate, combine or switchINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2004H. Schuster Summary Despite the benefits of statin therapy, cholesterol management remains suboptimal and many patients do not achieve their recommended low-density lipoprotein cholesterol (LDL-C) goals. The use of insufficient doses, limited drug effectiveness and poor patient compliance may contribute to the treatment gap. Options for improving lipid management include dose titration, combination therapy or prescribing a more efficacious statin. LDL-C reductions are generally modest when patients' current statin dose is titrated, and there may be an increased potential for adverse effects. Combining statin therapy with another lipid-modifying agent can provide additional LDL-C reductions, but cost, tolerability and compliance should be considered. In general, switching to a more efficacious statin is a cost-effective way of enabling more patients to achieve recommended targets without increasing dosages. When considering the options available, physicians should balance efficacy, cost and safety to enable more patients to attain LDL-C goals and achieve greater therapeutic gain from statin treatment. [source] Antidiabetic activity of flavone from Ipomoea Batatas leaf in non-insulin dependent diabetic ratsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 1 2007Rui Zhao Summary The effects of flavone extracted from Ipomoea batatas leaf (FIBL) on body weight, blood glucose, serum lipid profiles, serum insulin and free radicals in rats with non-insulin dependent diabetes mellitus (NIDDM) were studied. FIBL treatment (25, 50, 100 mg kg,1) for 2 weeks resulted in a significant decrease in the concentration of plasma triglyceride (TG), plasma cholesterol (TC) and weight in NIDDM rats. Furthermore, FIBL markedly decreased fasting plasma insulin level, blood glucose (FBG) level, low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) levels and significantly increased the Insulin Sensitive Index (ISI) and superoxide dismutase (SOD) level in NIDDM rats. In addition, flavone extracted from I. batatas leaf did not show any physical or behavioural signs of toxicity. More significantly, our data demonstrate the FIBL at the dose of 50 mg kg,1 body weight exhibited the optimal effect. The above results suggest that flavone extracted from I. batatas leaf could control blood glucose and modulate the metabolism of glucose and blood lipid, and decrease outputs of lipid peroxidation and scavenge the free radicals in non-insulin dependent diabetic rats. [source] Aging and the Prevalence of Cardiovascular Disease Risk Factors in Older American Indians: The Strong Heart StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2007Dorothy A. Rhoades MD OBJECTIVES: To describe longitudinal changes in the prevalence of major cardiovascular disease (CVD) risk factors in aging American Indians. DESIGN: Population-based ongoing epidemiological study. SETTING: The Strong Heart Study is a study of CVD and its risk factors. Standardized examinations were repeated in 1993 to 1995 and again in 1997 to 1999. PARTICIPANTS: A diverse cohort of 4,549 American Indians aged 45 to 74 at the initial examinations in 1989 to 1991. MEASUREMENTS: Changes in the prevalence of hypertension, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), current smoking, and type 2 diabetes mellitus. RESULTS: The prevalence of hypertension rose rapidly and steadily with aging. A nonsignificant decrease in LDL-C was seen in men, and men and women initially had rapid increases in the prevalence of low HDL-C. The prevalence of smoking decreased, but the prevalence of diabetes mellitus continued to rise for men and women. CONCLUSION: Overall, unfavorable changes in CVD risk factors were seen in the aging participants and will likely be reflected in worsening morbidity and mortality. [source] Prospective Association Between Low and High Total and Low-Density Lipoprotein Cholesterol and Coronary Heart Disease in Elderly MenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2004J. David Curb MD Objectives: To examine the relationship between total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) in elderly men. Design: Prospective. Setting: Population based. Participants: A sample of 2,424, Japanese-American men aged 71 to 93 was used. Measurements: Six years of data on incident fatal plus nonfatal CHD were examined. Results: Analysis revealed a significant U-shaped relationship between age-adjusted CHD rates and both TC and LDL-C. The ranges of TC and LDL-C with the lowest risk of CHD were 200 to 219 mg/dL and 120 to 139 mg/dL, respectively. As cholesterol concentrations declined and increased beyond these ranges, the risk of CHD increased. These U-shaped relationships remained significant after adjusting for age and other risk factors. Conclusion: The U-shaped associations between TC and LDL-C and CHD imply a complex relationship between lipids and CHD in late life. The results indicate that elevated lipid levels should continue to be treated in healthy elderly individuals, as they are in those who are younger, although pharmacologically lowering lipids to excessively low levels in the elderly may warrant further study, as does the contribution of subclinical frailty to the relationship of lipids to CHD risk. [source] Antihyperlipidemic activity of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, in streptozotocin-diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2010Govindasamy Chandramohan Abstract Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on carbohydrate metabolism was investigated, and its antihyperglycemic effect was shown previously (Chandramohan et al., Eur J Pharmacol 2008;590:437,443). In this study we investigated the effect of 3-HMX on plasma and tissue lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180,200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. The normal and diabetic rats were treated with 3-HMX (40 mg/kg BW/day) for 45 days. The levels of total cholesterol, triglycerides, free fatty acids, and phospholipids were assayed in the plasma besides lipoprotein-cholesterol (high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very low density lipoprotein-cholesterol (VLDL-C)) and tissues (liver, kidney, heart, and brain). Total cholesterol, triglyceride, free fatty acid, and phospholipid (LDL-C and VLDL-C in plasma only) levels increased in plasma and tissues significantly, whereas plasma HDL-C significantly decreased in diabetic rats. Treatment with 3-HMX or glibenclamide reversed the above-mentioned changes and improved toward normalcy. Histological study of liver also confirmed the biochemical findings. Thus administration of 3-HMX is able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:95,101, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20317 [source] Efficacy and safety of DALI LDL-apheresis at high blood flow rates: A prospective multicenter studyJOURNAL OF CLINICAL APHERESIS, Issue 4 2003T. Wendler Abstract Direct adsorption of lipids (DALI) is the first LDL-apheresis method compatible with whole blood. Usually, the blood flow rate is adjusted at 60,80 ml/min, which results in session times of about 2 hr. The present study was performed to test the safety and efficacy of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] removal by DALI at high blood flow rates in order to reduce treatment time. Thirteen chronic DALI patients in seven centers suffering from hypercholesterolemia (LDL-C 162 ± 42 mg/dl at baseline) and coronary artery disease were treated on a weekly or biweekly basis by DALI apheresis. The blood flow rate QB was held constant for at least two sessions, respectively, and was increased from 60 to 80, 120, 160, 200, and 240 ml/min. All patients had pre-existing av-fistulas. The anticoagulation was performed by a heparin bolus plus ACD-A at a ratio of citrate: blood ranging from 1:20 to 1:90. Clinically, the sessions were well tolerated and only 26/201 sessions (12%) of the treatments were fraught with minor adverse events. Acute LDL-C reductions (derived from LDL-C levels determined by lipoprotein electrophoresis) averaged 72/66/60/53/50/48% for QB = 60/80/120/160/200/240 ml/min. Lp(a) reductions were 68/67/62/60/58/56%, whereas HDL-C losses were ,10%. Routine blood chemistries and blood cell counts remained in the normal range. Treatment times averaged 142/83/45 min at Qb = 60/120/240 ml/min. On average, DALI LDL-apheresis could be performed safely and effectively at high blood flow rates up to at least 120 ml/min in patients with good blood access, which significantly reduced treatment time from 142 to 83 min (,42%). J. Clin. Apheresis 18:157,166, 2003. © 2003 Wiley-Liss, Inc. [source] Direct adsorption of low-density lipoprotein and lipoprotein(a) from whole blood: Results of the first clinical long-term multicenter study using DALI apheresis,JOURNAL OF CLINICAL APHERESIS, Issue 4 2002T. Bosch Abstract Direct adsorption of lipoproteins (DALI) is the first low-density lipoprotein (LDL)-apheresis technique by which atherogenic LDL and lipoprotein(a) (Lp(a)) can be selectively removed from whole blood without plasma separation. The present study was performed to evaluate the efficacy, selectivity and safety of long-term DALI apheresis. Sixty-three hypercholesterolemic coronary patients were treated by weekly DALI sessions. Initial LDL-cholesterol (C) plasma levels averaged 238 ± 87 mg/dl (range 130,681 mg/dl). On average, 34 sessions (1,45) were performed processing 1.5 patient blood volumes. The primary aim was to acutely reduce LDL-C by ,60% per session. To this end, three different adsorber sizes could be employed, i.e., DALI 500, 750, and 1,000, which were used in 4, 73, and 23% of the 2,156 sessions, respectively. On average, 7,387 ml of blood were processed in 116 min per session. This resulted in the following mean acute changes: LDL-C 198 , 63 mg/dl (,69%), Lp(a) 86 , 32 mg/dl (,64%), triglycerides 185 , 136 mg/dl (,27%). HDL-C (,11%) and fibrinogen (,15%) were not significantly influenced. The mean long-term reduction of LDL-C was 42% compared to baseline while HDL-C slightly increased in the long run (+4%). The selectivity of LDL removal was good as recoveries of albumin, immunoglobulins, and other proteins exceeded 85%. Ninety-five percent of 2,156 sessions were completely uneventful. The most frequent adverse effects were hypotension (1.2% of sessions) and paresthesia (1.1%), which were probably due to citrate anticoagulation. Access problems had to be overcome in 1.5%, adsorber and hardware problems in 0.5% of the sessions. In this multicenter long-term study, DALI apheresis proved to be an efficient, safe, and easy procedure for extracorporeal LDL and Lp(a) elimination. J. Clin. Apheresis 17:161,169, 2002. © 2002 Wiley-Liss, Inc. [source] Gender- and Age-Related Differences in Treatment and Control of Cardiovascular Risk Factors Among High-Risk Patients With AnginaJOURNAL OF CLINICAL HYPERTENSION, Issue 7 2005Katharine H. Hendrix PhD Dyslipidemic, hypertensive patients (N=48,863) were stratified by gender, age, and angina (n=2502) vs. nonangina (n=46,358) status. Comparing 95% confidence intervals yielded significant differences in treatment and cardiovascular risk factor control between subgroups. More men than women bad low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (angina, 43.94-43.96 vs. 34.42-34.50; nonangina, 32.43-32.43 vs. 17.25-17.25) and 100-129 mg/dL (angina, 32.12-32.14 vs. 35.10-35.18; nonangina, 53.86-53.86 vs. 32.44-32.44). More women than men had LDL-C >130 mg/dL (angina, 27.68-27.72 vs. 23.91-23.93; nonangina, 38.70-38.70 vs. 35.38-35.39). Women were less likely than men to receive statins (angina, 69.95-69.99 vs. 82.11-82.13; nonangina, 59.80-59.80 vs. 63.72-63.72), any antilipidemic medication at all (angina, 25.93-25.97 vs. 13.48-13.48; nonangina, 36.73-36.73 vs. 30.73-30.73), or to have current cholesterol measurements (angina, 56.82-56.88 vs. 34.54-34.56; nonangina, 45.77-45.77 vs. 39.75-39.75). Primary care providers treat high-risk patients relatively aggressively; however, opportunities to forestall cardiovascular disease may be missed in hypertensive, dyslipidemic women whose LDL-C is often not measured and controlled. [source] Serum microminerals and the indices of lipid metabolism in an apparently healthy populationJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2003Clifford Abiaka Abstract Serum copper and zinc concentrations were measured in 560 apparently healthy Kuwaitis (238 males and 322 females) aged 15,80 years to assess micromineral effect on the indices of lipid metabolism. Following the recommended guidelines of the European Atherosclerosis Society (EAS) and the National Cholesterol Education Program Expert Panel (NCEPEP), the incidence of dyslipidemia was assessed from enzymatic assay data of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations. Males had significantly lower TC (P=0.029) and HDL-C (P<0.0001) levels than females, while TG were significantly (P=0.023) lower in females. The prevalence of hypercholesterolemia, hypertriglyceridemia, elevated LDL-C, and low HDL-C levels were 35, 30, 22, and 13%, respectively. Copper did not correlate with zinc (r = ,0.067, P = 0.135) but was positively associated with TC (r=0.196, P<0.0001), LDL-C (r=0.134, P = 0.003), TG (r = 0.092, P=0.039), and age (r=0.281, P<0.0001). It is concluded that unlike in animal studies, copper excess in humans is associated with hyperlipidemia and therefore will predispose to atherosclerosis. J. Clin. Lab. Anal. 17:61,65, 2003. © 2003 Wiley-Liss, Inc. [source] A systematic review and meta-analysis on the therapeutic equivalence of statinsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2010T.-C. Weng MSc (Clin Pharm) Summary Background:, Statins are the most commonly prescribed agents for hypercholesterolemia because of their efficacy and tolerability. As the number of patients in need of statin therapy continues to increase, information regarding the relative efficacy and safety of statins is required for decision-making. Objective:, This study will use systematic review to compare the efficacy and safety profiles of different statins at different doses and determine the therapeutically equivalent doses of statins to achieve a specific level of low-density lipoprotein cholesterol (LDL-C) lowering effect. Methods:, Publications of head-to-head randomized controlled trials (RCTs) of statins were retrieved from the Oregon state database (1966,2004), MEDLINE (2005-April of 2006), EMBASE (2005-April of 2006), and the Cochrane Controlled Trials Registry (up to the first quarter of 2006). The publications were evaluated with predetermined criteria by a reviewer before they were included in the review. The mean change in cholesterol level of each statin was calculated and weighted by number of subjects involved in each RCT. Where possible, meta-analysis was performed to generate pooled estimates of the cholesterol lowering effect of statins and the difference between statins. Results:, Seventy-five studies reporting RCTs of head-to-head comparisons on statins were included. Most studies had similar baseline characteristics, except the rosuvastatin related studies. A daily dose of atorvastatin 10 mg, fluvastatin 80 mg, lovastatin 40,80 mg, and simvastatin 20 mg could decrease LDL-C by 30,40%, and fluvastatin 40 mg, lovastatin 10,20 mg, pravastatin 20,40 mg, and simvastatin 10 mg could decrease LDL-C by 20,30%. The only two statins that could reduce LDL-C more than 40% were rosuvastatin and atorvastatin at a daily dose of 20 mg or higher. Meta-analysis indicated a statistically significant but clinically minor difference (<7%) between statins in cholesterol lowering effect. Comparisons of coronary heart disease prevention and safety could not be made because of insufficient data. Conclusions:, At comparable doses, statins are therapeutically equivalent in reducing LDL-C. [source] Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metforminJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2009G. Derosa MD PhD Summary Background and objective:, Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. Methods:, We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run-in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7·5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean ± standard deviation), 300 ± 60, 12·5 ± 2·5, and 2500 ± 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post-prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA1c), fasting (FPI) and post-prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run-in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. Results and discussion:, Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA1c (P < 0·01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0·01 vs. baseline), PPG (P < 0·01 vs. baseline), and on HOMA index (P < 0·05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA1c (P < 0·05 vs. baseline), FPG (P < 0·01 vs. baseline), PPG (P < 0·05 vs. baseline), and HOMA index (P < 0·05 vs. baseline). No significant change was observed in TC, LDL-C, HDL-C, Tg, Apo A-I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin-resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. Conclusion:, Nateglinide improved glycemic control better than glibenclamide in combination with metformin. [source] Metformin,pioglitazone and metformin,rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndromeJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2006G. Derosa MD PhD Summary Background and objective:, Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. Methods:, This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration ,6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA1c), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. Results and discussion:, No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA1c decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. Conclusion:, For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not. [source] Goal attainment for multiple cardiovascular risk factors in community-based clinical practice (a Canadian experience)JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 1 2009Pendar Farahani MD MSc Abstract Background, The primary goal in the clinical management of atherosclerotic cardiovascular (CV) disease is to reduce major CV risk factors. A single risk factor approach has been traditionally used for demonstrating effectiveness of therapeutic interventions designed to reduce CV risk in clinical trials, but a global CV risk reduction approach should be adopted when assessing effectiveness in the clinical practice setting. Objectives, To explore combined goal achievement for low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose and systolic-diastolic blood pressure, in patients with dyslipidemia on pharmacotherapy in community-based clinical practices across Canada. Methods, In a cross-sectional study, patients filling a prescription for any antihyperlipidemia therapy in selected pharmacies in Ontario, Quebec, British Columbia and Nova Scotia were recruited. Family physicians of the participating patients were requested to provide information from the patient's medical record. Ten-year CV risk was identified for each patient according to the Framingham criteria. Results, High-risk patients comprised 52% of the patient population; 34% were moderate-risk and 14% were low-risk. Patients had a mean of 2.8 CV risk factors; high-risk 3.7, moderate-risk 2.3 and low-risk 1.2. LDL-C goal attainment was observed in 62%, 79% and 96% of patients in high-risk, moderate-risk and low-risk strata respectively. BP goal was achieved in high-risk patients 58%, moderate-risk 83% and low-risk 95%. Glucose levels were below the threshold in 91% of patients. Complete global CV risk reduction was achieved in only 21%, 66% and 92% of high-risk, moderate-risk and low-risk strata respectively. Conclusion, This study illustrates that many patients with dyslipidemia in the Canadian population, and in particular the high-risk patients, did not meet the therapeutic targets for specific CV risk factors according to the Canadian guidelines. Overall, 54% of patients failed to achieve a state of complete global CV risk reduction. [source] Amelioration of Cadmium-Induced Oxidative Stress, Impairment in Lipids and Plasma Lipoproteins by the Combined Treatment with Quercetin and ,-Tocopherol in RatsJOURNAL OF FOOD SCIENCE, Issue 7 2010S. Milton Prabu Abstract:, Cadmium (Cd) exposure results in numerous pathological consequences including oxidative stress and dyslipidemia. The present study was designed to investigate the efficacy of combined treatment with quercetin (QE) and ,-tocopherol (AT) against Cd-induced oxidative stress and alterations in lipids and lipoproteins in the plasma and liver of rats. Oral administration of Cd (5 mg/kg bw/d) for 4 wk has shown a significant (P < 0.05) increase in thiobarbituric acid reactive substances (TBARS), lipid hydro peroxides (LOOH), total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), free fatty acids (FFA), phospholipids (PL), triglycerides (TGs), and the activity of hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) in plasma with a significant (P > 0.05) reduction in the levels of reduced glutathione (GSH), high density lipoprotein cholesterol (HDL-C), and the activity of lecithin cholesterol acyl transferase (LCAT) in plasma. In addition, the levels of hepatic thiobarbituric acid reactive substances (TBARS), LOOH, conjugated dienes (CD), protein carbonyls (PC), and the activity of HMG-CoA reductase, levels of cholesterol, FFA, and TGs were significantly (P > 0.05) increased and the level of PL is significantly (P > 0.05) decreased along with the decreased activity of LCAT in the liver of Cd-treated rats. Oral supplementation with QE (50 mg/kg bw/d) and AT (50 mg/kg bw/d) for 4 wk in Cd intoxicated rats significantly (P > 0.05) has reduced the plasma levels of TBARS, LOOH, GSH, cholesterol, FFA, TGs, VLDL-C, LDL-C, and the activity of HMG-CoA and significantly (P > 0.05) has increased the activity of LCAT and the plasma levels of HDL-C. The oral supplementation also significantly (P > 0.05) has reduced the hepatic oxidative stress markers, cholesterol, TGs, FFA, and significantly (P > 0.05) has increased the LCAT activity and the PL in liver. Our results indicate that the combined treatment with QE and AT has normalized all the previously mentioned biochemical parameters in Cd-intoxicated rats than the individual treatments. The combined treatment has provided remarkable protection against Cd-induced oxidative stress and alterations in lipid metabolism and, thereby, reduced the Cd-mediated cardiovascular diseases. [source] Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in ChinaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2009Hongyun Lu Abstract Background and Aim:, To investigate the relationship between human leptin receptor (LEPR) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients complicated with or without non-alcoholic fatty liver disease (NAFLD). Methods:, Two hundred and sixteen cases of newly diagnosed T2DM patients (104 cases complicated with NAFLD) and 108 cases of normal glucose tolerances (NGT) were recruited. Hemi-nested polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR-direct sequence analysis were conducted to detect the polymorphism of LEPR G3057A variation. Plasma leptin levels were measured by enzyme-linked immunosorbent assay kit. Plasma lipid and glucose metabolic parameters were measured routinely. Liver ultrasound was carried out for all subjects. Results:, T2DM patients complicated with NAFLD had higher plasma insulin, leptin, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels than those without NAFLD and NGT subjects. The variant frequency at nucleotide 3057 G,A transversion was 76.0% in type 2 diabetic patients complicated with NAFLD, which was also significantly higher than those without NAFLD (62.1%) and NGT cases (53.2%). There was also significant difference in genotype distribution between the three groups (,2 = 14.63, P < 0.01). Conclusion:, The polymorphism of LEPR gene 3057 probably contributes to the onset of NAFLD by regulating lipid metabolism and affecting insulin sensitivity. [source] ApoB but not LDL-cholesterol is reduced by exercise training in overweight healthy men.JOURNAL OF INTERNAL MEDICINE, Issue 2 2007Exercise Study, Results from the 1-year randomized Oslo Diet Abstract. Objectives., (i) To estimate changes in apoB and apoB/apoA-I, reflecting the balance between atherogenic and anti-atherogenic lipoprotein particles, by exercise training and compare with changes in LDL-C and TC/HDL-C ratio, and (ii) To compare strengths of relationships between physical fitness and various lipoprotein variables Design, setting, and subjects., The study was a 1-year open randomized trial comprising 219 healthy middle-aged subjects aged 40,49 years who were allocated to exercise or no exercise, dietary advice or no advice in a 2 × 2 factorial design. This study includes 188 men who completed the trial, 45 to diet, 48 to exercise, 58 to diet + exercise and 37 to control. Interventions., Exercise; supervised endurance exercise three times a week. Diet; reduce weight, increase intake of fish and reduce total fat intake. Main outcome measure., One-year change in apoB and apoB/apoA-I ratio. Results., Exercisers decreased their ApoB and ApoB/ApoA-I values significantly compared to non-exercisers. LDL-C was not, but LDL-C/HDL-C was marginally but statistically significantly reduced by exercise. One-year change in ApoB and ApoB/ApoA-I correlated more strongly to 1-year changes in physical fitness than LDL-C or LDL-C/HDL-C. Adjusting for changes in LDL-C or LDL-C/HDL-C did not influence the correlation between changes in fitness and ApoB or ApoB/ApoA-I. However, adjusting for changes in ApoB or ApoB/ApoA-I wiped out the correlation between change in fitness and LDL-C or LDL-C/HDL-C. Relationships weakened when adjusting for changes in waist circumference, but Apo B or ApoB/ApoA-I still correlated significantly to changes in fitness. Conclusion., Physical exercise reduced the atherogenic burden as experienced by the reduction in apoB or apoB/apoA-I levels, but not by LDL-C in healthy middle-aged men. Possibly, regular physical activity might increase the LDL-C particle size, thereby making LDL less atherogenic. Monitoring of apolipoproteins rather than the cholesterol moiety of lipoproteins might improve the assessment of lipoprotein changes after exercise training. [source] Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic menJOURNAL OF INTERNAL MEDICINE, Issue 6 2003J. Skogsberg Abstract. Objectives., Peroxisome proliferator activated receptor delta (PPARD) is a transcription factor implicated in the regulation of genes involved in cholesterol metabolism. We recently discovered a common polymorphism in the 5,-untranslated region (5,-UTR) of the human PPARD, +294T/C, that is associated with an increased plasma low-density lipoprotein cholesterol (LDL-C) concentration in healthy subjects. Whether the +294C allele is associated with LDL-C elevation independently of the background lipoprotein phenotype and whether it confers increased risk of coronary heart disease (CHD) is unknown. Against this background, we investigated the relationships between the PPARD polymorphism and plasma lipoprotein concentrations and the risk for contracting CHD in the West of Scotland Coronary Prevention Study (WOSCOPS). Design., A nested case,control study of participants in a randomized double-blind placebo-controlled trial of pravastatin in mildly-to-moderately hypercholesterolaemic men. Subjects., A total of 580 cases of incident CHD and 1160 individuals who remained free of CHD (controls). Main outcome measures., Plasma lipoprotein con-centrations and risk of CHD according to PPARD genotype. Results., Individuals carrying the rare PPARD +294C allele had a significantly lower high-density lipoprotein cholesterol (HDL-C) concentration than subjects homozygous for the common T-allele. Homozygous carriers of the C-allele also showed a tendency towards higher risk of CHD compared with homozygous carriers of the T-allele. In addition, a gene,gene interaction involving the PPARD polymorphism and the PPAR alpha L162V polymorphism may influence the plasma LDL-C concentration. Conclusions., PPARD plays a role in cholesterol metabolism in man. [source] | ||||||||||||||||||||||||||||||||||||||||