Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Risk stratification and prognostic implication of plasma biomarkers in nondiabetic patients with stable coronary artery disease: the role of high-sensitivity C-reactive protein. Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease Serum Plant Sterols Associate with Gallstone Disease Independent of Weight Loss and Non-Alcoholic Fatty Liver Disease Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease[S] Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial (TTA)n polymorphism in 3-hydroxy-3-methylglutaryl-coenzyme A and response to atorvastatin in coronary artery disease patients. Simvastatin maintains steady patterns of GFR and improves AER and expression of slit diaphragm proteins in type II diabetes. Two Patterns of Adipokine and Other Biomarker Dynamics in a Long-Term Weight Loss Intervention Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid. Carotid intima media thickness, inflammatory markers, and endothelial activation markers in HIV Patients with lipoatrophy increased at 48 weeks regardless of use of rosiglitazone or placebo. Novel Biomarkers to Improve the Prediction of Cardiovascular Event Risk in Type 2 Diabetes Mellitus The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia. Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons. Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe. Simple advice on lifestyle habits and long-term changes in biomarkers of inflammation and vascular adhesion in healthy middle-aged men
BACKGROUND The rise in LDL with egg feeding in lean insulin-sensitive ( LIS ) participants is 2- and 3-fold greater than in lean insulin-resistant ( LIR ) and obese insulin-resistant ( OIR ) participants , respectively . OBJECTIVE We determined whether differences in cholesterol absorption , synthesis , or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis . DESIGN Plasma sterols were measured by gas chromatography-mass spectrometry in a r and om subset of 34 LIS , 37 LIR , and 37 OIR participants defined by the insulin sensitivity index ( S(I ) ) and by BMI criteria selected from a parent group of 197 participants . Cholestanol and plant sterols provide a measure of cholesterol absorption , and lathosterol provides a measure of cholesterol synthesis . RESULTS The mean ( ±SD ) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS , 3.25 ± 1.06 in LIR , and 2.82 ± 1.08 in OIR participants . After adjustment for age and sex , the relations of the absorption sterol-cholesterol ratios were as follows : LIS > OIR ( P < 0.001 ) , LIS > LIR ( P < 0.001 ) , and LIR > OIR ( P = 0.11 ) . Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants , 0.95 ± 0.47 in the LIR participants , and 1.29 ± 0.55 in the OIR participants . After adjustment for age and sex , the relations of lathosterol-cholesterol ratios were as follows : LIS < OIR ( P < 0.001 ) , LIS < LIR ( P = 0.03 ) , and LIR < OIR ( P = 0.002 ) . Total sterol concentrations were positively associated with S(I ) and negatively associated with obesity , whereas lathosterol correlations were the opposite . CONCLUSIONS Cholesterol absorption was highest in the LIS participants , whereas cholesterol synthesis was highest in the LIR and OIR participants . Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I ) and to decrease cholesterol overproduction in LIR and OIR persons To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols , these noncholesterol sterols , fatty acids , and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a r and omly selected Finnish male population sample of 100 subjects , aged 50 years , who had normal dietary habits .  Serum levels of cholesterol precursors , desmosterol and lathosterol  ( in terms of micrograms/mg cholesterol ) , were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein ( HDL ) cholesterol , and positively related to overall cholesterol synthesis and serum very low density lipoprotein ( VLDL ) cholesterol . Serum levels of the plant sterols , campesterol and sitosterol , exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat , the linoleic acid contents of plasma and dietary lipids , the amount of dietary plant sterols ( as indicated by fecal output ) , fractional and absolute absorption of dietary cholesterol , and HDL cholesterol , but were inversely related to the overall cholesterol synthesis and VLDL cholesterol . Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption , dietary plant sterols , and biliary cholesterol secretion , and that of sitosterol with dietary plant sterols , cholesterol synthesis , fractional cholesterol absorption , and biliary cholesterol secretion . Thus , the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and , since gas liquid chromatographic determination of these sterols is quite simple , their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies STUDY OBJECTIVES To evaluate the implication of plasma biomarkers to future cardiovascular events in nondiabetic patients with stable coronary artery disease ( CAD ) . Design s and setting s : Prospect i ve , follow-up study at a tertiary referral center . Patients and measurement : Serial plasma biomarkers including high-sensitivity C-reactive protein ( hsCRP ) , homocysteine , soluble adhesion molecules , von Willebr and factor , and lipid profiles were determined before coronary angiograms in a series of nondiabetic CAD patients with stable angina . Among them , 75 consecutive patients who received coronary revascularization ( 48 coronary interventions and 27 coronary bypass surgeries ) later and another 75 age- and gender-matched patients who preferred medical treatment were both enrolled . In patients of each group , major cardiovascular events including cardiac death , nonfatal myocardial infa rct ion , new or repeated coronary revascularization , and hospitalization for unstable angina , stroke , or peripheral artery disease were prospect ively followed up for at least 6 months . RESULTS Patients were followed up to 40 months ( median , 18 months ) . The incidences of major cardiovascular events were similar between the two groups . For patients with medical treatment , plasma levels of hsCRP , homocysteine , low-density lipoprotein , and the ratio of total cholesterol ( TC ) to high-density lipoprotein cholesterol ( HDL-C ) were significantly higher in those with cardiovascular events than those without . However , only hsCRP > 0.1 mg/dL ( relative risk [ RR ] , 2.78 ; 95 % confidence interval [ CI ] , 1.21 to 6.41 ; p = 0.016 ) and TC/HDL-C ratio > 4.8 ( RR , 2.42 ; 95 % CI , 1.04 to 5.65 ; p = 0.041 ) were independent predictors by multivariable analysis . For patients with revascularization , basal plasma hsCRP levels were higher in those with cardiovascular events than those without ( p = 0.04 ) . However , no biochemical markers could predict future major cardiovascular events in these patients . CONCLUSIONS In nondiabetic patients with CAD , basal plasma hsCRP levels were increased with future cardiovascular events regardless of different treatment strategies . Both plasma hsCRP level and TC/HDL-C ratio independently predict future cardiovascular events , confirming the role of plasma biomarkers in clinical risk stratification especially in patients with medical treatment Background This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease ( NAFLD ) with hypercholesterolemia . Methods Serum sample s of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated .  Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC – MS)/MS . These data were then compared with those of 36 sex- and age-matched healthy controls . In addition , changes in these markers produced by treatment with pitavastatin were evaluated . Results Serum non-cholesterol sterols , reflecting intestinal cholesterol absorption , were significantly lower in the NAFLD patients compared to the controls , and the cholesterol synthesis marker , the ratio of lathosterol to cholesterol , was not significantly different between the two groups . Serum proportions of liver X receptor α ( LXRα ) lig and oxysterols ( ratios to cholesterol ) were significantly elevated in the NAFLD patients compared to the controls . The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance ( HOMA-IR ) were significantly correlated . The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment , from 3 months after initiation of the treatment , and the suppression remained significant during the observation period . The markers representing cholesterol absorption were unchanged at 3 months , but had significantly increased at 12 months . Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment . Conclusions : We speculate that serum LXRα lig and oxysterol levels ( relative to cholesterol ) could be surrogate markers of insulin resistance , and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD Background Gallstone disease ( GD ) has been associated with low serum levels of plant sterols . We evaluated the impact of laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and non-alcoholic fatty liver disease ( NAFLD ) on the association of GD with low levels of serum plant sterols . Methods Two hundred forty-two consecutive morbidly obese patients were recruited to this prospect i ve study . Histological analysis of liver biopsy to diagnose NAFLD was performed . Bile sample was taken during the LRYGB . Associations of GD with serum non-cholesterol sterol to cholesterol ratios , measured using gas liquid chromatography and with mRNA expression of genes participating in the cholesterol , bile , and fatty acid metabolism in the liver , were analyzed . Results Out of the 242 participants , 95 had GD .  Lower weight ( p = 0.002 ) and female sex ( p = 0.0006 ) were associated with GD . Serum plant sterols , campesterol ( p = 0.003 ) , sitosterol ( p = 0.002 ) , and avenasterol ( p = 0.015 ) , were lower in patients with GD compared to those without GD . This association remained significant after adjustment for NAFLD , use of statin medication , and previous laparoscopic cholecystectomy ( LCC ) . Levels of sitosterol ( p = 0.001 ) and campesterol ( p = 0.001 ) remained lower in obese individuals with GD also after obesity surgery . Liver mRNA expression of genes regulating cholesterol synthesis and bile metabolism was increased in individuals with GD . Conclusions Serum plant sterols were lower in patients with GD independent of NAFLD , history of LCC , use of statin medication , and weight loss after LRYGB . Low serum plant sterols in patients with GD suggest potentially inherited alterations in sterol absorption and biliary transport in subjects susceptible for GD No indices are currently available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment . We aim ed to investigate whether cholesterol synthesis and absorption markers can predict the cholesterol-lowering response to statin . Total 306 statin-naïve patients with high risk of coronary heart disease ( CHD ) were treated with atorvastatin 20 mg/day for 1 month . Cholesterol synthesis and absorption markers and LDL cholesterol ( LDL-C ) levels were measured before and after treatment . Atorvastatin decreased LDL-C by 36.8 % ( range : decrease of 74.5 % to increase of 31.9 % ) . Baseline cholesterol synthesis marker lathosterol and cholesterol absorption marker campesterol codetermined the effect of atorvastatin treatment . The effect of cholesterol lowering by atorvastatin was significantly associated with baseline lathosterol levels but modified bidirectionally by baseline campesterol levels . In patients with the highest baseline campesterol levels , atorvastatin treatment decreased cholesterol absorption by 46.1 % , which enhanced the effect of LDL-C lowering . Atorvastatin treatment increased cholesterol absorption by 52.3 % in those with the lowest baseline campesterol levels , which attenuated the effect of LDL-C reduction . Especially those with the highest lathosterol but the lowest campesterol levels at baseline had significantly less LDL-C reduction than those with the same baseline lathosterol levels but the highest campesterol levels ( 27.3 % versus 42.4 % , P = 0.002 ) . These results suggest that combined patterns of cholesterol synthesis /absorption markers , rather than each single marker , are potential predictors of the LDL-C-lowering effects of atorvastatin in high-risk CHD patients Cholesterol homeostasis , defined as the balance between absorption and synthesis , influences circulating cholesterol concentrations and subsequent coronary heart disease ( CHD ) risk . Statin therapy targets the rate-limiting enzyme in cholesterol bio synthesis and is efficacious in lowering CHD events and mortality . Nonetheless , CHD events still occur in some treated patients . To address differences in outcome during pravastatin therapy ( 40 mg/day ) , plasma markers of cholesterol synthesis ( desmosterol , lathosterol ) and fractional cholesterol absorption ( campesterol , sitosterol ) were measured , baseline and on treatment , in the Prospect i ve Study of Pravastatin in the Elderly at Risk trial participants with ( cases , n = 223 ) and without ( controls , n = 257 ) a CHD event .  Pravastatin therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL-cholesterol concentrations to a similar extent in cases and controls . Decreased concentrations of the cholesterol synthesis markers desmosterol ( −12 % and −11 % ) and lathosterol ( −50 % and −56 % ) and increased concentrations of the cholesterol absorption markers campesterol ( 48 % and 51 % ) and sitosterol ( 25 % and 26 % ) were observed on treatment , but the magnitude of change was similar between cases and controls . These data suggest that decreases in cholesterol synthesis in response to pravastatin treatment were accompanied by modest compensatory increases in fractional cholesterol absorption . The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been used clinical ly for lowering total and low-density lipoprotein cholesterol . Interindividual pharmacological differences observed with this treatment have been attributed to genetic differences . The aim of this study was to assess the association in the low-density lipoprotein cholesterol reduction by atorvastatin and (TTA)n polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene in patients with coronary artery disease . Changes in total cholesterol levels , triglycerides , high-sensitivity C-reactive protein and free F(2)-isoprostanes were also evaluated . In an open study , patients received 40 mg atorvastatin daily for 8 weeks . Genotyping was done through polymerase chain reaction . The genotype distribution of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (TTA)n polymorphism was : > 10/>10 in 22 out of 64 patients ( 34 % ) , > 10/10 in 14 out of 64 patients ( 22 % ) and 10/10 in 28 out of 64 patients ( 44 % ) . The reduction of low-density lipoprotein cholesterol levels by atorvastatin was not different between allelic variants (TTA)n repeat polymorphism . Reductions in high-sensitivity C-reactive protein were observed in atorvastatin-treated patients with alleles > 10/>10 and 10/10 . Free F(2)-isoprostanes and total cholesterol were also significantly lower after treatment for all alleles , irrespective of type of polymorphism . In conclusion , the changes induced by atorvastatin treatment on low-density lipoprotein cholesterol , total cholesterol , triglycerides , high-sensitivity C-reactive protein and free F(2)-isoprostane concentrations were not related to the presence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase polymorphism (TTA)n The factors determining the course of glomerular filtration rate ( GFR ) and albumin excretion rate ( AER ) and the expression of mRNA of slit diaphragm ( SD ) and podocyte proteins in microalbuminuric , hypertensive type II diabetic patients are not fully understood . GFR , AER , and SD protein mRNA were studied in 86 microalbuminuric , hypertensive , type II diabetics at baseline and after 4-year r and om double-blind treatment either with 40 mg simvastatin  ( Group 1 ) or with 30 g cholestyramine ( Group 2 ) per day . Both groups had at baseline a GFR decay per year in the previous 2 - 4 years of 3 ml/min/1.73 m(2 ) . Both Groups 1 and 2 showed a significant decrease of low-density lipoprotein cholesterol levels after simvastatin and cholestyramine treatment ( P<0.01 ) . No change from base line values was observed as for hs-C-reactive protein and interleukin-6 . A significant decrease of 8-hydroxydeoxyguanosine urinary excretion was observed after simvastatin treatment . GFR did not change from baseline with simvstatin , whereas a decrease was observed with cholestyramine treatment ( simvastatin vs cholestyramine : -0.21 vs -2.75 ml/min/1.73 m(2 ) , P<0.01 ) . AER decreased in Group 1 ( P<0.01 ) , but not in Group 2 patients . Real-time polymerase chain reaction measurement of mRNA SD proteins ( CD2AP , FAT , Actn 4 , NPHS1 , and NPHS2 ) significantly increased in kidney biopsy specimens after simvastatin , but not cholestyramine treatment . Simvastatin , but not cholestyramine , 4-year treatment maintains steady patterns of GFR , and improves AER and expression of SD proteins in type II diabetes , despite similar hypocholesterolemic effects in circulation OBJECTIVE Long-term dietary intervention frequently induces a rapid weight decline followed by weight stabilization/regain . Here , we sought to identify adipokine biomarkers that may reflect continued beneficial effects of dieting despite partial weight regain . RESEARCH DESIGN AND METHODS We analyzed the dynamics of fasting serum levels of 12 traditional metabolic biomarkers and novel adipokines among 322 participants in the 2-year Dietary Intervention R and omized Controlled Trial ( DIRECT ) of low-fat , Mediterranean , or low-carbohydrate diets for weight loss . RESULTS We identified two distinct patterns : Pattern A includes biomarkers ( insulin , triglycerides , leptin , chemerin , monocyte chemoattractant protein 1 , and retinol-binding protein 4 ) whose dynamics tightly correspond to changes in body weight , with the trend during the weight loss phase ( months 0–6 ) going in the opposite direction to that in the weight maintenance/regain phase ( months 7–24 ) ( P < 0.05 between phases , all biomarkers ) . Pattern B includes biomarkers ( high molecular weight adiponectin , HDL cholesterol [ HDL-C ] , high-sensitivity C-reactive protein [ hsCRP ] , fetuin-A , progranulin , and vaspin ) that displayed a continued , cumulative improvement ( P < 0.05 compared with baseline , all biomarkers ) throughout the intervention . These patterns were consistent across sex , diabetic groups , and diet groups , although the magnitude of change varied . Hierarchical analysis suggested similar clusters , revealing that the dynamic of leptin ( pattern A ) was most closely linked to weight change and that the dynamic of hsCRP best typified pattern B. CONCLUSIONS hsCRP , HDL-C , adiponectin , fetuin-A , progranulin , and vaspin levels display a continued long-term improvement despite partial weight regain . This may likely reflect either a delayed effect of the initial weight loss or a continuous beneficial response to switching to healthier dietary patterns Ratios of cholestanol , campesterol , and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency . Here , a possible link between these ratios and biliary secretion rates of cholesterol was investigated . Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones . Seven were treated with ursodeoxycholic acid ( UDCA ) ( 1,000 mg/d ) . Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers , who received either placebo or UDCA ( 750 mg/d ) .  Biliary cholesterol secretion was significantly lower , whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA .  A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed . In volunteers , administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios . Even 4 weeks after discontinuing UDCA administration , campesterol and sitosterol were still significantly higher than pretreatment levels , which was also true for the campesterol-cholesterol ratio after 8 weeks . The results suggest that the ratios of cholestanol , campesterol , and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates Rosiglitazone may be useful for the treatment of antiretroviral therapy-associated lipoatrophy , but an association with cardiovascular disease ( CVD ) has been question ed in diabetics . We evaluated rosiglitazone 's effect on surrogate markers of CVD in HIV-infected individuals with lipoatrophy . HIV(+ ) patients with lipoatrophy on thymidine-sparing regimens were r and omized to rosiglitazone vs. placebo for 48 weeks . We serially assessed carotid IMT , fasting metabolic profiles , tumor necrosis factor (TNF)-α , soluble receptors ( sTNFRI and II ) , interleukin (IL)-6 , high-sensitivity C-reactive protein ( hsCRP ) , myeloperoxidase ( MPO ) , and endothelial activation markers [ von Willebr and factor ( vWF ) , soluble intercellular cell adhesion molecules-1 ( sICAM-1 ) , and vascular cell adhesion molecules-1 ( sVCAM-1 ) ] . Seventy-one subjects enrolled : 17 % were female and 51%were white . Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group ( p = 0.04 ) . At 48 weeks , common carotid artery ( CCA ) IMT changed significantly ( p ≤ 0.05 ) within but not between the groups ( p = 0.36 ) : the median ( IQR ) increase was 0.10 ( 0.05 , 0.25 ) mm and 0.15 ( 0 , 0.25 ) mm in the rosiglitazone and placebo groups , respectively . hsCRP , sTNFRI and II , sVCAM-1 , and vWF changed significantly ( p ≤ 0.02 ) within but not between groups . Total cholesterol increased significantly in the rosiglitazone group ( p = 0.008 ) . In our study of virologically controlled subjects with lipoatrophy , rosiglitazone did not independently increase carotid IMT , endothelial activation , and inflammatory cytokines Background We evaluated the ability of 23 novel biomarkers representing several pathophysiological pathways to improve the prediction of cardiovascular event ( CVE ) risk in patients with type 2 diabetes mellitus beyond traditional risk factors . Methods and Results We used data from 1002 patients with type 2 diabetes mellitus from the Second Manifestations of ARTertial disease ( SMART ) study and 288 patients from the European Prospect i ve Investigation into Cancer and Nutrition‐NL ( EPIC‐NL ) . The associations of 23 biomarkers ( adiponectin , C‐reactive protein , epidermal‐type fatty acid binding protein , heart‐type fatty acid binding protein , basic fibroblast growth factor , soluble FMS‐like tyrosine kinase‐1 , soluble intercellular adhesion molecule‐1 and ‐3 , matrix metalloproteinase [MMP]‐1 , MMP‐3 , MMP‐9 , N‐terminal prohormone of B‐type natriuretic peptide , osteopontin , osteonectin , osteocalcin , placental growth factor , serum amyloid A , E‐selectin , P‐selectin , tissue inhibitor of MMP‐1 , thrombomodulin , soluble vascular cell adhesion molecule‐1 , and vascular endothelial growth factor ) with CVE risk were evaluated by using Cox proportional hazards analysis adjusting for traditional risk factors . The incremental predictive performance was assessed with use of the c‐statistic and net reclassification index ( NRI ; continuous and based on 10‐year risk strata 0–10 % , 10–20 % , 20–30 % , > 30 % ) . A multimarker model was constructed comprising those biomarkers that improved predictive performance in both cohorts . N‐terminal prohormone of B‐type natriuretic peptide , osteopontin , and MMP‐3 were the only biomarkers significantly associated with an increased risk of CVE and improved predictive performance in both cohorts . In SMART , the combination of these biomarkers increased the c‐statistic with 0.03 ( 95 % CI 0.01–0.05 ) , and the continuous NRI was 0.37 ( 95 % CI 0.21–0.52 ) . In EPIC‐NL , the multimarker model increased the c‐statistic with 0.03 ( 95 % CI 0.00–0.03 ) , and the continuous NRI was 0.44 ( 95 % CI 0.23–0.66 ) . Based on risk strata , the NRI was 0.12 ( 95 % CI 0.03–0.21 ) in SMART and 0.07 ( 95 % CI −0.04–0.17 ) in EPIC‐NL . Conclusions Of the 23 evaluated biomarkers from different pathophysiological pathways , N‐terminal prohormone of B‐type natriuretic peptide , osteopontin , MMP‐3 , and their combination improved CVE risk prediction in 2 separate cohorts of patients with type 2 diabetes mellitus beyond traditional risk factors . However , the number of patients reclassified to a different risk stratum was limited AIM To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption , we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis , lipid and glucose metabolism , and markers of obesity and inflammation . METHODS A total of 120 patients with dyslipidemia ( 46 men ; mean age 66.5 years ) , who had not achieved the low density lipoprotein cholesterol ( LDL-C ) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy , were enrolled and additionally treated with ezetimibe ( 10 mg/day ) for 12 weeks . RESULTS Compared to the baseline , LDL-C was reduced by 19.2 % ( p<0.001 ) after ezetimibe monotherapy and by 24.7 % ( p<0.001 ) after co-administration with ezetimibe and any statin . Ezetimibe therapy decreased cholesterol absorption markers and increased a cholesterol synthesis marker . Treatment with ezetimibe reduced the fasting serum insulin level ( p<0.05 ) and HbA1c ( p<0.05 ) , increased serum adiponectin ( p<0.01 ) , and showed a significant decrease of high-sensitive C-reactive protein ( hsCRP , p<0.01 ) . No adverse events occurred during the study . CONCLUSION Thus , cholesterol absorption inhibition by ezetimibe is an important therapeutic strategy since LDL-C and cholesterol absorption markers had a positive correlation . Ezetimibe not only reduced the serum LDL-C level but also improved glucose metabolism as well as obesity and inflammation markers . These findings support the benefit of ezetimibe as a new option for the treatment of dyslipidemia BACKGROUND Because of hyperglycemia and hyperinsulinemia , diabetic persons have higher cholesterol synthesis and lower cholesterol absorption rates than do nondiabetic persons . Differences in plant sterol efficacy between diabetic and nondiabetic persons have not been examined . OBJECTIVE The objective was to compare the degree of response of plasma lipid concentrations and glycemic control to plant sterol consumption in a controlled diet between hypercholesterolemic type 2 diabetic and nondiabetic subjects . DESIGN Fifteen nondiabetic subjects and 14 diabetic subjects participated in a double-blinded , r and omized , crossover , placebo-controlled feeding trial . The diet included 1.8 g/d of either plant sterols or cornstarch placebo over 21 d , separated by a 28-d washout period . RESULTS Plant sterol consumption significantly reduced ( P < 0.05 ) LDL-cholesterol concentrations from baseline in both nondiabetic and diabetic subjects by 15.1 % and 26.8 % , respectively . The diabetic subjects had significantly ( P < 0.05 ) lower absolute concentrations of total cholesterol after treatment than did the nondiabetic subjects ; however , there was no significant difference in the percentage change from the beginning to the end of the trial . There was also a significant decrease ( P < 0.05 ) in absolute non-HDL-cholesterol concentrations after treatment in both groups . CONCLUSIONS The results showed that plant sterols are efficacious in lowering LDL cholesterol and non-HDL cholesterol in both diabetic and nondiabetic persons .  Plant sterol consumption may exist as a dietary management strategy for hypercholesterolemia in persons with type 2 diabetes In addition to their expected effects on lipid profile , lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation . Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols . Although it is known that an additional reduction of low-density lipoprotein cholesterol ( LDL-C ) levels can be induced by the combination of ezetimibe with statins , it is not known if this can enhance some pleiotropic effects , which may be useful in slowing the atherosclerotic process . This study assessed the effects of simvastatin and ezetimibe , in monotherapy or in combination , on markers of endothelial function and insulin sensitivity . Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were r and omly allocated to 2 groups receiving either ezetimibe ( 10 mg/d ) or simvastatin ( 20 mg/d ) for 12 weeks , after which the drugs were combined for both groups for an additional 12-week period . Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy . Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated . As expected , both groups receiving drugs in isolation significantly reduced total cholesterol , LDL-C , apolipoprotein B , and triglyceride levels ; and additional reductions were found after the combination period ( P < .05 ) . After 12 weeks of monotherapy , plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group . No change in homeostasis model assessment of insulin resistance index , area under the curve of insulin , and adiponectin levels was observed after either the monotherapies or the combined therapy . However , simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes . Our findings support cl aims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia . Alternatively , a deleterious effect of ezetimibe on the endothelial function is suggested , considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels .  Simvastatin and ezetimibe , in isolation or in combination , do not interfere with insulin sensitivity Background / Objectives : Lifestyle habits , vascular function and inflammation are components in the development of cardiovascular disease ( CVD ) . We investigated whether simple advice on dietary and exercise habits given ( at a single time point ) to hypercholesterolemic men affects circulating biomarkers of inflammation and vascular adhesion . Subjects/ Methods : In total , 157 men ( age 46±5 years ) with mild hypercholesterolemia were r and omized to four intervention groups , diet ( D , n=40 ) , exercise ( E , n=39 ) , diet and exercise ( DE , n=39 ) or controls ( C , n=39 ) and serum concentrations of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , soluble intercellular adhesion molecule 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule 1 ( sVCAM-1 ) and soluble E-selectin ( sE-selectin ) were quantified at baseline and after a 6-month intervention period . Results : The intervention applied in this study , that is , simple advice on lifestyle changes given at a single time point , had a modest effect on inflammatory biomarkers and soluble vascular adhesion molecules . The most apparent alterations were found for individuals in group DE , who responded with significant reductions in sICAM-1 , −28 ( −41 to −14 μg/l ) and sE-selectin , −3.6 ( −6.9 to −0.3 μg/l ) after 6 months . None of the groups had altered their concentrations of sVCAM-1 , CRP or IL-6 significantly after the intervention . In all individuals combined , we found changes in apolipoprotein B ( apoB ) to predict alterations in sICAM-1 ( β=0.21 ) and sE-selectin ( β=0.26 ) , independently of changes in inflammation and other adhesion molecules . Conclusions : These observations indicate that even small efforts to improve diet and physical activity can influence biomarkers of vascular function in individuals at increased risk for CVD . ApoB was identified as an important determinant of this improvement , which adds further support to the notion of apoB as a critical target in cardiovascular prevention
In general , markers for cholesterol absorption and synthesis displayed reciprocal patterns , showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis .
Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified , suggesting that metabolic disorders can be classified as ' cholesterol absorbers or cholesterol synthesizers ' .
Non-cholesterol sterols are vali date d biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis .
However , their use in metabolic disturbances has not been systematic ally explored .
Therefore , we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders .