The Effect of HMG-CoA Reductase Inhibitor on Insulin Resistance in Patients Undergoing Peritoneal Dialysis Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial. Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial. Atorvastatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes Lifestyle Intervention and Adipokine Levels in Subjects at High Risk for Type 2 Diabetes Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients. Insulin and leptin concentrations in obese humans during long-term weight loss. Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women Comparative effects of metformin and pioglitazone on omentin and leptin concentrations in patients with newly diagnosed diabetes: A randomized clinical trial Weight status and dietary intake determine serum leptin concentrations in pregnant and lactating women and their infants. Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy humans. Weight loss due to a very low calorie diet differentially affects insulin sensitivity and interleukin-6 serum levels in nondiabetic obese human subjects. Serum adipokines as biomarkers of beta-cell function in patients with type 1 diabetes: positive association with leptin and resistin and negative association with adiponectin. Coenzyme Q10 does not improve peripheral insulin sensitivity in statin-treated men and women: the LIFESTAT study. The effect of simvastatin-ezetimibe combination therapy on adipose tissue hormones and systemic inflammation in patients with isolated hypercholesterolemia. Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia. Lovastatin for reduction of leptin in nondialysis patients with type 2 diabetic nephropathy. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. The effects of oral contraceptives including low-dose estrogen and drospirenone on the concentration of leptin and ghrelin in polycystic ovary syndrome. Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy. Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak.
Background Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease ( ESRD ) . Although statins exert pleiotropic effects , it is uncertain whether statin therapy improves insulin resistance in these patients . In this prospect i ve r and omized controlled trial , we aim ed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis ( PD ) . Methods Patients were r and omized into a statin group ( n = 35 ) or a control group ( n = 35 ) . The statin group received 10 mg per day of rosuvastatin for 6 months . We determined insulin resistance by homeostatic model assessment of insulin resistance ( HOMA-IR ) index . Serum concentrations of adipokines such as adiponectin , leptin , and resistin were measured using enzyme-linked immunosorbent ( ELISA ) assay . As inflammatory markers , high sensitive C-reactive protein ( hsCRP ) and interleukin-6 were also measured . Results There were no significant differences in baseline characteristics between the two groups . Compared to baseline value , statin treatment significantly decreased HOMA-IR index from 2.37 ± 1.08 to 2.05 ± 0.82 ( P = 0.014 ) . There was a concordant decrease in hsCRP levels in the statin group ( 2.05 ± 1.57 to 1.21 ± 0.84 mg/L , P < 0.001 ) , but such improvements were not observed in the control group . When between-group differences in these parameters were compared , hsCRP levels were more decreased in the statin group than in the control group ( P = 0.021 for between-group difference ) , whereas HOMA-IR index was not ( P = 0.189 for between-group difference ) . During this period , statin treatment did not result in the improved adipokine profiles . Conclusion This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment . Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients OBJECTIVE Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin . This study aim ed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome . METHODS In this pilot , r and omized , double-blind , placebo-controlled trial , subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were r and omly assigned to curcumin ( n = 59 ; 1000 mg/d ) or a placebo ( n = 58 ) for 8 wk . Serum adiponectin and leptin concentrations were determined before and after intervention . The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using r and om-effects meta analysis . RESULTS Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels ( P < 0.001 ) and a reduction in serum leptin concentrations ( P < 0.001 ) . Serum leptin : adiponectin ratio was also improved by curcumin ( P < 0.001 ) . These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response . Meta analysis suggested that curcumin supplementation can increase adiponectin levels by 76.78 % ( 95 % CI : 6.14 - 147.42 ; P = 0.0330 ) , and reduce leptin by 26.49 % ( 95 % CI : -70.44 to 17.46 ) , however this latter effect size did not reach statistical significance ( P = 0.238 ) . CONCLUSIONS Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome . This trial was registered at the UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ) under Trial No. UMIN000018339 OBJECTIVE Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged . Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin , as well as combined therapy , on fasting plasma glucose , insulin resistance index , adipokines ( leptin , resistin , adiponectin ) and levels of proinflammatory cytokines ( TNF-α , IL-6 ) in patients with impaired fasting glucose ( IFG ) and mixed hyperlipidemia . MATERIAL S AND METHODS 67 patients were r and omly assigned to four treatment arms : monotherapy with atorvastatin , monotherapy with fenofibrate , combined therapy ( fenofibrate and torvastatin ) or therapeutic lifestyle change . The study lasted for 90 days . All participants received counseling regarding proper diet and physical activity . RESULTS Compared to the control subjects , prediabetic patients exhibited elevated plasma levels of leptin , resistin , TNF-α and IL-6 , and a lower plasma level of adiponectin . All therapeutic interventions result ed in significant alterations in the lipid profile . Insulin resistance index ( HOMA-IR ) was reduced after treatment with fenofibrate . The effect of atorvastatin on insulin resistance was comparable to therapeutic lifestyle change alone . Therapy with hypolipidemic drugs caused increases in adiponectin levels and decreases in leptin and resistin . An additive effect of the combined treatment on plasma IL-6 level was also observed . CONCLUSIONS Fenofibrate-based treatment was associated with improved insulin sensitivity . Atorvastatin did not cause a deterioration in insulin sensitivity . Hypolipidemic therapies result ed in significant changes in the proinflammatory cytokine network as well as in adipokine levels . At the end of the study the measured parameters nearly resembled those of the healthy subjects Phytoestrogens and training could be effective to reduce cardiovascular and type 2 diabetes mellitus risk factors in postmenopausal women . Nevertheless , the impact of their combination on adipokines and systemic inflammation was never investigated . The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women . Fifty-two obese women aged between 50 and 70 years were r and omly assigned to ( 1 ) exercise with placebo ( EX + PL ; n = 25 ) or ( 2 ) exercise with phytoestrogens ( EX + PHY ; n = 27 ) . Body weight , waist circumference , fat mass , and lean body mass ( dual-energy x-ray absorptiometry ) were assessed . Fasting plasma glucose and insulin , adiponectin , leptin , and C-reactive protein ( CRP ) levels were obtained after a 12-hour overnight fast . Total energy intake was measured with a 3-day dietary record . All measurements were performed before and after the 6-month intervention . Although energy intake remained unchanged , body composition was improved in all women ( all Ps < .02 ) . Plasma CRP and leptin levels decreased in both groups similarly ( all Ps < .03 ) , whereas plasma adiponectin and insulin did not change with exercise combined with placebo or phytoestrogens . Correlation analyses showed that homeostasis model assessment of insulin resistance ( r = -0.58 , P = .02 ) and fasting insulin levels ( r = -0.42 , P = .02 ) at baseline were both correlated with changes in leptin levels . Baseline fasting glucose ( r = -0.36 , P = .03 ) and adiponectin ( r = 0.45 , P = .005 ) levels were associated with changes in CRP concentrations . Although mixed exercise program combined with phytoestrogens does not seem to provide any additional effect , mixed training improves systemic inflammation and leptin concentrations in obese postmenopausal women Background : In addition to lipid lowering , further pleotropic effects of statins have been postulated . We aim ed to study if the various pleotropic effects are due indirectly to the modulation of adipocytokines . Material s and methods : We studied the effect of atorvastatin on insulin sensitivity and the plasma adiponectin and leptin concentrations . Our r and omized open labeled study had 29 hyperlipidemic Type 2 diabetic patients ( 14 females , 15 males , mean age 60.0±2.2 yr ) . They were r and omized into three 12-week atorvastatin intervention types . Each day patients were given either 10 mg ( no.=10 ) , 20 mg ( no.=10 ) or 40 mg ( no.=9 ) . Evaluations were performed before and after intervention . Results : All baseline characteristics were statistically identical in the 3 groups . Drop in total cholesterol , LDL-cholesterol , and triglyceride levels were measured at the end . With 10 mg the drop was 30 % , 37 % , and 30 % . The 20 mg group was 43 % , 54 % , and 34 % . The 40 mg group was 42 % , 51 % , and 27 % . Groups had no significant change of body mass index , HDL-cholesterol , and glycated hemoglobin levels . Also , levels of insulin , adiponectin , leptin , homeostasis model assessment index ( HOMA ) and Quantitative Insulin Sensitivity Check Index ( QUICKI ) stayed the same . Pooled parameters of all 29 patients showed no difference in levels of insulin , adiponectin , leptin , HOMA , and QUICKI before and after treatment . Conclusions : Atorvstatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes OBJECTIVE —We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin , adiponectin , and resistin as biomarkers for lifestyle-induced improvements in glucose metabolism and insulin resistance . RESEARCH DESIGN AND METHODS —In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht , 147 men and women with impaired glucose tolerance ( IGT ) were r and omized to either a combined diet- and -exercise intervention or a control program . At baseline and after 1 year , an oral glucose tolerance test , an exercise test , and anthropometric measurements were performed . After 1 year , complete data of 103 subjects ( 50 intervention and 53 control subjects ) were obtained . RESULTS —Lifestyle intervention reduced plasma leptin concentrations ( −14.2 % ) in IGT subjects but did not alter plasma adiponectin ( −0.3 % ) or resistin ( −6.5 % ) concentrations despite marked improvements in glucose tolerance and insulin resistance . CONCLUSIONS —Changes in leptin concentration were related to improvements in insulin sensitivity independent of changes in body composition Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage . While intentional weight loss is thought to improve prognosis , its impact on these adipokines is unclear . This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during  weight loss .  Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism , the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-r and omized , controlled study design .  Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention . While leptin was associated with fat mass , adiponectin was not , and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation . The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss . Dietary pattern was without effect on either adipokine . Mechanisms not directly related to dietary pattern , weight loss , or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines BACKGROUND The effect of statins on insulin resistance is controversial and poorly studied in nondiabetic subjects . In addition , the effect of statins on leptin and adiponectin has never been studied . METHODS Forty healthy nondiabetic volunteers ( 22 men and 18 women ) aged 28 to 72 were r and omized either to placebo or pravastatin 40 mg daily for a 12-week period . Insulin resistance , assessed using the Quantitative Insulin Sensitivity Check Index ( QUICKI ) , as well as serum leptin and adiponectin levels , was measured at baseline and at the end of therapy . RESULTS Pravastatin treatment decreased total cholesterol , low-density lipoprotein cholesterol , and triglycerides levels by 24 % , 32 % , and 14 % , respectively ( P < .05 for all ) , but did not affect glucose and insulin levels , the ( QUICKI ) index , and adiponectin and leptin levels . When stratification was performed according to QUICKI index or sex , no significant differences were observed in the prevalues and postvalues of leptin , adiponectin , or QUICKI index in the pravastatin group . Adiponectin , leptin , and QUICKI index were statistically higher in women than in men ( P < .001 for both variables ) . Adiponectin was negatively correlated with body mass index ( BMI ; r = -0.39 , P < .05 ) and positively correlated with the QUICKI index ( r = 0.54 , P < .001 ) and with high-density lipoprotein cholesterol ( r = 0.50 , P < .01 ) . The relation between adiponectin and QUICKI index remained significant after adjustment for sex and BMI ( P = .005 and P = .007 , respectively ) . Leptin was only related to BMI ( r = 0.57 , P < .001 ) and to sex ( P < .001 ) with no significant correlations with lipid parameters or QUICKI index . Both sex and BMI are independent predictors of leptin ( P < .001 and P < .001 ) . CONCLUSION A 12-week treatment with pravastatin 40 mg/d does not change the QUICKI index and leptin and adiponectin levels in healthy volunteers . In addition , our results emphasize the importance of sex and BMI in the determination of both adiponectin and leptin . Adiponectin was also related to QUICKI index , whereas this relation was not found with leptin BACKGROUND Leptin is likely to be involved in the homeostasis of body weight . Insulin is suggested to regulate both short-term and long-term circulating leptin levels . The present study aims to assess the relation between insulin and leptin levels in obese humans . METHODS Some 53 obese subjects ( body mass index 35.1 + /- 3.9 kg m-2 ( mean + /- SD ) ) were prescribed a hypocaloric diet and r and omized to either a placebo or the intestinal lipase inhibitor orlistat for 2 years .  Serum leptin and insulin levels were determined repeatedly during these 2 years ( 5 times in the fasting condition and twice after an oral glucose load ) . RESULTS Leptin concentrations appeared to be regulated at a specific level for each individual throughout the weight-loss period . The BMI explained 39.7 % of the total variance in leptin levels , the body-fat distribution 17.2 % , individual characteristics 30.3 % ; and the fasting serum insulin concentration 1.0 % . After a mean weight loss of 7.7 + /- 4.9 kg , the time-integrated insulin response to an oral glucose load was significantly lower but the leptin response remained unchanged . CONCLUSIONS The BMI is the main determinant of the circulating leptin concentration in obese humans . Individual characteristics seem to determine the leptin level , given the BMI . In a short-term observational study in obese humans , changes of insulin levels do not appear to be correlated to changes in leptin levels Leptin is thought to be a lipostatic signal that contributes to body weight regulation . Zinc might play an important role in appetite regulation and its administration stimulates leptin production . However , there are few reports in the literature on its role on leptin levels in the obese population . The present work asseses the effect of zinc supplementation on serum leptin levels in insulin resistance ( IR ) . A prospect i ve double-blind , r and omized , clinical , placebo-controlled study was conducted . Fifty-six normal glucose-tolerant obese women ( age : 25–45 yr , body mass index [ BMI ] = 36.2 ±2.3 kg/m2 ) were r and omized for treatment with 30 mg zinc daily for 4 wk . Baseline values of both groups were similar for age , BMI , caloric intake , insulin concentration , insulin resistance , and zinc concentration in diet , plasma , urine , and erythrocytes . Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment ( HOMA ) . The determinations of zinc in plasma , erythrocytes , and 24-h urine were performed by using atomic absorption spectrophotometry . After 4 wk , BMI , fasting glucose , and zinc concentration in plasma and erythrocyte did not change in either group , although zinc concentration in the urine increased from 385.9±259.3 to 470.2±241.2±μg/24 h in the group with zinc supplementation ( p<0.05 ) . Insulin did not change in the placebo group , whereas there was a significant decrease of this hormone in the supplemented group . HOMA also decreased from 5.8±2.6 to 4.3±1.7 ( p<0.05 ) in the zinc-supplemented group but did not change in the placebo group . Leptin did not change in the placebo group . In the zinc group , leptin was 23.6±12.3 μg/L and did not change . More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation ( with higher doses or longer intervals ) or different measures AIMS To assess the effects of two commonly used oral hypoglycemic medications metformin and pioglitazone on serum concentrations of omentin and leptin in patients with newly diagnosed type 2 diabetes . METHODS In a clinical trial setting ( NCT01593371 ) , patients were r and omly allocated to either metformin 1000 mg daily ( n=41 ) , or pioglitazone 30 mg daily ( n=50 ) . Serum concentrations of omentin and leptin were measured at baseline and after 12weeks . Patients ' weight , waist circumference , blood pressure , fasting plasma glucose , fasting insulin , HbA1c , highly sensitive C-reactive protein , and serum lipids were also measured at the two visits . RESULTS Baseline concentrations of omentin and leptin were not different between the two arms of the trial . After three months , metformin decreased both omentin and leptin concentrations in women , and leptin concentrations only in men . On the other h and , pioglitazone reduced both adipokines only in women , but not men . Univariate and multivariate ANCOVA models revealed that both interventions are equally effective in reducing omentin concentration ( p=0.497 for women and 0.344 for men in multivariate models controlling for the effects of confounding variables ) . Similarly , neither medication was more effective in reducing leptin concentrations after three months ( p=0.822 for women and 0.441 for men in multivariate models ) . CONCLUSIONS Metformin and pioglitazone at pharmacologic doses are equally effective in alteration of serum omentin and leptin concentrations in patients with diabetes , albeit sex differences in response to medications exist . Implication of these findings on long term management and complication prevention of diabetes needs to be eluci date Leptin regulates energy homeostasis and immune and metabolic functions . Highly elevated leptin concentrations during pregnancy may be associated with aberrations in maternal metabolism and long-term health consequences both in women and children . The objective of the present study was to evaluate whether dietary counselling , probiotic supplementation , maternal characteristics or dietary intake during pregnancy has an impact on serum leptin concentrations in women , cord blood or in children . A total of 256 pregnant women were r and omised to a control group ( n 85 ) or to receive dietary counselling with probiotics ( n 85 ) or placebo ( n 86 ) . Dietary counselling aim ed at affecting the type of fat used and to increase the amount of fibre in the women 's diet . Women 's dietary intake and serum leptin concentrations were analysed at the first and third trimesters of pregnancy and at 1 month postpartum . Furthermore , leptin concentrations were measured from the cord blood and from children 's serum at 1 and 6 months of age . Weight status and dietary composition were the key determinants of leptin concentrations . Specifically , high dietary fibre and low SFA intakes were related to low serum leptin concentrations in women . Female sex and birth weight were associated with higher infant leptin , whereas cord blood leptin was additionally affected by maternal leptin concentration and protein intake . Probiotics or dietary counselling did not affect leptin concentrations . Weight control to recommended levels and modification of diet towards higher fibre and lower SFA intakes during pregnancy may through leptin concentrations provide health benefits to both women and children To examine the effects of acute altitude-induced hypoxia on the hormonal and metabolic response to ingested glucose , 8 young , healthy subjects ( 5 men and 3 women ; age , 26 + /- 2 years ; body mass index , 23.1 + /- 1.0 kg/m(2 ) ) performed 2  r and omized trials in a hypobaric chamber where a 75-g glucose solution was ingested under simulated altitude ( ALT , 4300 m ) or ambient ( AMB , 362 m ) conditions . Plasma glucose , insulin , C-peptide , epinephrine , leptin , and lactate concentrations were measured at baseline and 30 , 60 , 90 , and 120 minutes after glucose ingestion during both trials . Compared with AMB , the plasma glucose response to glucose ingestion was reduced during the ALT trial ( P = .04 ) . There were no differences in the insulin and C-peptide responses between trials or in insulin sensitivity based on the homeostasis model assessment of insulin resistance . Epinephrine and lactate were both elevated during the ALT trial ( P < .05 ) , whereas the plasma leptin response was reduced compared with AMB ( P < .05 ) . The data suggest that the plasma glucose response is suppressed at ALT , but this is not due to insulin per se because insulin and C-peptide levels were similar for both trials . Elevated plasma epinephrine and lactate during ALT are indicative of increased glycogenolysis , which may have masked the magnitude of the reduced glucose response . We conclude that , during acute altitude exposure , there is a rapid metabolic response that is accompanied by a shift in the hormonal milieu that appears to favor increased glucose utilization Inflammatory mechanisms are involved in the pathogenesis of type 2 diabetes with interleukin (IL)-6 being particularly important . While long term exercise has been shown to be associated with reduction in IL-6 serum levels in several reports , the discussion on the effect of dietary intervention on IL-6 serum levels is controversial . In the present study , we aim ed to investigate the effect of weight loss due to a very low calorie diet ( VLCD ) on insulin sensitivity and IL-6 serum levels in nondiabetic obese human individuals . 10 patients with obesity were examined during 12 weeks of a VLCD ( 800 kcal/d ) . Body composition was measured by impedance analysis . Blood sample s were taken before , during , and after the dietary intervention .  Leptin , adiponectin , and IL-6 serum levels were measured by ELISA . The body weight decreased significantly from 123.9±6.2 - 103.5±5.6 kg with a significant reduction in body fat content ( 43.2±2.3 - 36.1±3.1 % ) . Leptin levels exhibited a significant decrease from 56.8±5.6 - 27.9±5.6 ng/ml while adiponectin levels increased significantly from 7.5±0.9 - 10.6±1.1 μg/ml . Thereby the leptin-to-adiponectin ratio , a novel marker for insulin sensitivity , significantly improved . Mean IL-6 serum concentrations were within the normal range ( 3.2±0.8 pg/ml ) before the study and were not significantly altered by the nutritional therapy . Despite improvement of insulin sensitivity , IL-6 serum levels did not change throughout the study period , suggesting that in nondiabetic obese human subjects IL-6 might have only a minor role in the impairment of insulin sensitivity BACKGROUND We investigated the adipokines adiponectin , leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes . METHODS One hundred and eighteen patients with type 1 diabetes ( 20.3 ± 7.5 years ) diagnosed < 5 years underwent st and ardized mixed meal test ( MMTT ) for 2 h.  Systemic concentrations of C-peptide , adiponectin , leptin and resistin obtained during MMTT were measured and compared between patient groups by multiple regression analysis . RESULTS Patients were divided by their adipokine levels in subgroups above or below the median level ( ' high versus low ' ) . High adiponectin levels ( > 10.6 µg/mL ) were associated with lower C-peptide compared to the low adiponectin subgroup ( p < 0.03 ) . Increased leptin or resistin concentrations associated positively with beta-cell function even after adjustment for metabolic confounders ( p < 0.04 ) . The described associations between adipokines and C-peptide concentrations persisted in Spearman correlation tests ( p < 0.05 ) . Serum adipokines fell during MMTT ( p < 0.05 ) . CONCLUSIONS Serum adipokine levels differentially correlate with beta-cell function in type 1 diabetes independent of BMI or metabolic control . Serum adipokines should be investigated as biomarkers of beta-cell function in prospect i ve studies and intervention trials in type 1 diabetes Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk of cardiovascular disease following high levels of blood cholesterol . There is a possible risk of new-onset diabetes mellitus with statin treatment but the mechanisms behind are unknown . Coenzyme Q10 ( CoQ10 ) supplementation has been found to improve glucose homeostasis in various patient population s and may increase muscle glucose transporter type 4 content . Our aim was to investigate if 8 weeks of CoQ10 supplementation can improve glucose homeostasis in simvastatin-treated subjects . Thirty-five men and women in treatment with a minimum of 40 mg of simvastatin daily were r and omized to receive either 2 × 200 mg/day of CoQ10 supplementation or placebo for 8 weeks . Glucose homeostasis was investigated with fasting blood sample s , oral glucose tolerance test ( OGTT ) and intravenous glucose tolerance test . Insulin sensitivity was assessed with the hyperinsulinemic-euglycemic clamp . Different indices were calculated from fasting sample s and OGTT as secondary measures of insulin sensitivity . A muscle biopsy was obtained from the vastus lateralis muscle for muscle protein analyzes . There were no changes in body composition , fasting plasma insulin , fasting plasma glucose , or 3-h glucose with intervention , but glycated hemoglobin decreased with time . Glucose homeostasis measured as the area under the curve for glucose , insulin , and C-peptide during OGTT was unchanged after intervention . Insulin secretory capacity was also unaltered after CoQ10 supplementation . Insulin sensitivity was unchanged but hepatic insulin sensitivity increased . No changes in muscle GLUT4 content was observed after intervention . CoQ10 supplementation does not change muscle GLUT4 content , insulin sensitivity , or secretory capacity , but hepatic insulin sensitivity may improve BACKGROUND Pleiotropic effects of ezetimibe have only been investigated in a few studies . The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low- grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia . METHODS The study included 69 patients with elevated cholesterol levels , who were allocated to one of the three groups treated for 12 weeks , respectively , with simvastatin ( 40 mg daily ) , simvastatin ( 40 mg daily ) plus ezetimibe ( 10 mg daily ) , or placebo .  Plasma levels of lipids , apolipoproteins , glucose homeostasis markers , leptin , adiponectin , visfatin , tumor necrosis factor-α ( TNF-α ) , free fatty acids ( FFA ) , and high-sensitive C-reactive protein ( hsCRP ) were determined on the allocation day and after 12 weeks of therapy . RESULTS Apart from improving lipid profile , simvastatin administered alone or in combination with ezetimibe , decreased plasma levels of hsCRP , FFA , leptin , visfatin , and TNF-α , as well as increased plasma levels of adiponectin . The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins , hsCRP , FFA , and the investigated adipokines . The effect of the combination therapy , but not of simvastatin , on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects . CONCLUSIONS The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe BACKGROUND Epidemiologic studies have shown that serum uric acid is a risk factor of coronary artery disease . In addition to fenofibrate , there is some evidence that atorvastatin may have a hypouricemic action , but the underlying mechanisms remain speculative . METHODS This r and omized trial was conducted to investigate the effects of atorvastatin and simvastatin on uric acid homeostasis in patients treated for primary hyperlipidemia . A total of 180 patients were enrolled ; patients were r and omly assigned to 40 mg/d of either atorvastatin or simvastatin .  Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment ; r and om urine sample s were simultaneously obtained for creatinine , sodium , and uric acid determinations . RESULTS Baseline serum uric acid levels correlated positively with the body mass index , serum insulin , creatinine , and triglyceride levels and inversely with serum HDL cholesterol levels . Both statins caused a favorable effect on lipids and a significant decrease in fibrinogen and high-sensitivity CRP levels . However , only atorvastatin reduced serum uric acid levels ( from 5.6 + /- 1.7 to 4.9 + /- 1.5 mg/dL , P < .0001 ) by augmenting its urinary fractional excretion ( from 10.4 % + /- 7.9 % to 12.0 % + /- 7.4 % , P < .01 ) . In a multivariate logistic regression analysis , the reduction of uric acid levels was independently associated with baseline serum uric acid concentration but not to other variables , including lipid parameters ( OR , 1.65 ; 95 % CI , 1.14 to 2.40 ; P = .008 ) . CONCLUSIONS Atorvastatin ( but not simvastatin ) significantly lowered serum uric acid levels . This result may be in favor of a preferable choice of atorvastatin for the treatment of hyperlipidemic patients presenting with hyperuricemia INTRODUCTION Diabetic Nephropathy ( DN ) is one of the main complications of diabetes mellitus , mostly ending to end-stage renal disease . Leptin and C-reactive protein ( CRP ) , as inflammatory markers implicated in the progression of DN , increase in diabetes mellitus , while transferrin and albumin , as members of anti-oxidant defense mechanism , are found to decline . MATERIAL S AND METHODS In a controlled clinical trial , 65 patients with type 2 DN were assigned to receive lovastatin or placebo , for 3 months , to assess statins ' impact on serum levels of leptin , CRP , transferrin , albumin , and lipid profile . RESULTS Serum levels of CRP ( 3.52 + /- 4.16 mg/dL to 2.84 + /- 3.06 mg/dL , P = .02 ) , leptin ( 10.78 + /- 8.30 mg/dL to 7.80 + /- 5.41 mg/dL , P = .006 ) , low-density lipoprotein cholesterol ( 116.16 + /- 46.54 mg/dL to 85.46 + /- 29.22 mg/dL , P = .001 ) , and total cholesterol ( 199.00 + /- 43.33 mg/dL to 164.67 + /- 35.19 mg/dL , P = .001 ) were lowered after lovastatin therapy . Mean serum level of high-density lipoprotein cholesterol increased ( 40.00 mg/dL to 42.80 mg/dL , P = .005 ) after the treatment . Lovastatin had no significant effect on albumin and transferrin . Placebo did not change any of the parameters after 3 months . CONCLUSIONS The effect of statins on the inflammatory markers involved in the development of DN is a new approach to evidence supporting the pleiotropic effect of this drug group CONTEXT Statins have been shown to improve hyper and rogenism in women with polycystic ovary syndrome ( PCOS ) . However , their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus . Because women with PCOS are prone to disturbances in glucose metabolism , statin therapy could also have negative effects . OBJECTIVE Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled 6-month follow-up study conducted at Oulu University Hospital , Finl and . PATIENTS Women with PCOS ( Rotterdam criteria ) were treated with atorvastatin ( 20 mg/d , n = 15 ) or placebo  ( n = 13 ) for 6 months . INTERVENTIONS Fasting serum sample s were collected at baseline and at 3 and 6 months . Oral and iv glucose tolerance tests were performed at 0 and 6 months . MAIN OUTCOME MEASURES And rogen secretion and glucose metabolism were measured . RESULTS Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity ( insulinogenic and Matsuda indexes ) decreased during 6 months of atorvastatin therapy . Serum levels of dehydroepi and rosterone sulfate decreased in the atorvastatin group , whereas no change was observed in serum testosterone levels . Levels of C-reactive protein , total and low-density lipoprotein-cholesterol , and triglycerides decreased significantly during statin therapy . CONCLUSIONS Atorvastatin therapy improves chronic inflammation and lipid profile , but it impairs insulin sensitivity in women with PCOS . Because women with PCOS have an increased risk of developing type 2 diabetes mellitus , the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease , and not only because of PCOS OBJECTIVE To evaluate short-term leptin and ghrelin concentrations in women with polycystic ovary syndrome ( PCOS ) who use low-dose oral contraceptives containing drospirenone .  DESIGN Prospect i ve study . SETTING Department of obstetrics and gynaecology in a university hospital . PATIENT(S ) Twenty women with PCOS were enrolled in the study . INTERVENTION(S ) A low-dose oral contraceptive containing ethinyl estradiol and drospirenone was given for three cycles . MAIN OUTCOME MEASURE(S ) Serum and rostenedione , free T , T , dehydroepi and rosterone sulphate , sex hormone-binding globulin , FSH , LH , E(2 ) , lipid profiles , leptin , and ghrelin levels were measured in each subject . Insulin resistance was estimated by the homeostasis model assessment -insulin resistance ( HOMA-IR ) . RESULT ( S ) While leptin concentrations did not change with therapy , ghrelin levels increased statistically . Baseline leptin concentrations were correlated positively with body mass index , waist-to-hip ratio , insulin , and HOMA-IR and negatively with ghrelin . After controlling for body mass index and waist-to-hip ratio in a partial correlation analysis , leptin levels were not correlated with these parameters . Ghrelin was inversely correlated with body mass index , waist-to-hip ratio , insulin , HOMA-IR , and free T. CONCLUSION ( S ) In patients with PCOS , an oral contraceptive containing ethinyl estradiol and drospirenone increases ghrelin levels but not leptin levels in a 3-month period . Ghrelin might be related to the metabolic and and rogenic changes in patients with PCOS OBJECTIVE We evaluated the long-term effects of rosuvastatin and simvastatin on insulin sensitivity and secretion in patients with well-controlled type 2 diabetes . METHODS After a 3 weeks run-in , 27 eligible patients were r and omly assigned to receive either rosuvastatin 20 mg daily ( Group 1 ) or simvastatin 20 mg daily ( Group 2 ) for 6 months ; thereafter they were switched to the other treatment for additional 6 months . Patients were recruited among individuals attending the outpatient service of the Diabetology Unit of the " Policlinico Tor Vergata " University Hospital , Rome , Italy . Serum lipids , glucose and insulin , glycated hemoglobin , C-reactive protein , TNF-α , leptin , adiponectin , insulin sensitivity by euglycemic-hyperinsulinemic clamp , β-cells function by HOMA-β were assessed at months 0 , 6 and 12 . Additionally , endothelial function was assessed by use of the brachial artery reactivity technique . RESULTS Besides marked reduction in lipid levels , glycated hemoglobin significantly increased from baseline after 12 months in both Group 1 ( + 0.8 ± 0.2 % , p < 0.001 ) and Group 2 ( + 0.9 ± 0.3 % ; p < 0.001 ) . Similar trends were observed for fasting glucose in both groups . No changes in insulin sensitivity were detected throughout the study , whereas HOMA-β significantly decreased from baseline after 12 months in both Group 1 ( -21.9 % , p < 0.01 ) and Group 2 ( -38.9 % ; p < 0.001 ) . In addition , both treatments similarly decreased C-reactive protein and leptin , as well as improved endothelial function . No changes in anthropometric measures were observed . CONCLUSIONS In well-controlled type 2 diabetic patients  both rosuvastatin and simvastatin significantly impaired glycemic control and insulin secretion , without affecting insulin sensitivity This issue of JAMA contains the latest US Preventive Services Task Force ( USPSTF ) recommendation statement on statins for prevention of cardiovascular disease in adults,1 along with the accompanying evidence report and systematic review 2 on which the recommendations are based . The evidence report summarized data from 19 trials including a total of 71 344 patients and concluded that statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease ( CVD ) events . Thus , the task force recommended “ initiating use of lowto moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10 % or greater ( B recommendation ) ” or “ 7.5 % to 10 % ( C recommendation ) .”1 Although the task force did their usual careful job of review ing the evidence , the evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation . The task force evidence report estimated an absolute benefit for use of statins of 0.40 % for all-cause mortality and 0.43 % for cardiovascular mortality and indicated that the absolute benefit was greater for patients at greater baseline risk.2 Notably , the evidence report did not exclude studies that included patients taking statins for secondary prevention , who have a higher baseline risk of cardiac events and death and thus are more likely to benefit from therapy that inflates the benefit attributed to a primary prevention population . The task force did perform a sensitivity analysis that excluded 3 trials with persons for whom there were prior “ hard ” cardiovascular events and obtained similar results of benefits ( eTable 5 in the article by Chou et al2 ) . This sensitivity analysis did not exclude WOSCOPS , which included patients receiving statins for secondary prevention—5 % had angina and 3 % had intermittent claudication,3 accounting for 15 % of the total weight in the meta- analysis . In contrast , a meta- analysis of 11 studies and 65 229 patients receiving statins for primary prevention , in which patients receiving statins for secondary prevention were excluded , found no benefit of statins for reducing all-cause mortality.4 The confidence intervals of these 2 analyses overlap , and the difference between these findings likely reflects differences in studies included . The USPSTF and authors of the evidence report did not have access to the primary data ( clinical study reports and anonymized patient-level data ) from the statin clinical trials . Rather , they had to rely on peer- review ed published reports as the basis for these recommendations . Exacerbating the potential bias , all of the trials included in the task force evidence report2 were industry-sponsored except 1 trial,5 and that trial contributed 0.2 % of the weight to the mortality calculation . Industry-sponsored studies have been shown to report greater benefit and lesser adverse effects than noncommercially sponsored trials of the same drugs.6 Whether this is true for statins and primary prevention of CVD is unknown . Among the 19 r and omized clinical trials of statins vs placebo or no statin included in the evidence report for the task force recommendations , only 15 reported all-cause mortality , 10 reported cardiovascular mortality , 12 reported fatal and nonfatal myocardial infa rct ion  , and 13 reported fatal and nonfatal stroke.2,7  Reliance on selective reporting of the most important outcomes , which are likely included in the clinical trial data , makes reporting bias possible . Furthermore , after allcause mortality , the comparative incidence of serious adverse events between treatment and control groups is arguably the second most important measure of the effect of active therapy in r and omized clinical trials . Underst and ing the evidence base in evaluating harms of statin therapy is also critically important . Although the benefits of any preventive therapy accrue according to risk of disease ( greater benefit in higher-risk patients ) , the harms of therapy usually distribute equally over all risk levels . Thus , persons at low risk have little chance of benefit but equal chance of harms and thus are more likely to have a net harm . The evidence base for harms of statins , despite the introduction of these drugs more than 20 years ago , is incomplete . Many of the trials did not ask about commonly reported statin effects , such as muscle pains and weakness , and only recorded myopathy , for which an increase in creatine kinase levels was required . Because most muscle problems do not involve an increase in creatine kinase levels , this leads to a significant underestimate of muscle problems . Other studies have estimated that closer to 20 % of statin users have muscle problems.8 Additionally , the actual trial data are largely held by the Cholesterol Treatment Trialists ’ Collaboration on behalf of the industry sponsor and have not been made available to other research ers , despite multiple requests over many years.9 Although reported rates of adverse events in clinical trials are low , this does not reflect the experience of clinicians who see patients who are taking statins . For instance , the experience of an NPR reporter with a calculated 2.9 % risk of heart disease over 10 years using the recommended American College of Cardiology/American Heart Association ( ACC/AHA ) risk calculator,10 but still prescribed a statin , and experiencing adverse effects from the medication , is typical of what many Related articles at jama.com
There was no association between the duration of statin therapy and changes in plasma leptin levels .
Furthermore , there was no differential effect of hydrophilic and lipophilic statins on plasma leptin concentrations .
OBJECTIVES The effects of statins on insulin sensitivity , metabolic homeostasis and adipokines in humans are controversial .
Several studies have investigated the impact of statin therapy on plasma leptin concentrations but the results have been inconsistent .
The aim of the present study was to conduct a systematic review and meta- analysis of available evidence to calculate the effect size of statin therapy in changing serum leptin concentrations .