Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Supplementation of α-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy Efficacy of glimepiride on insulin resistance, adipocytokines, and atherosclerosis. Extended-release niacin raises adiponectin and leptin. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Effects of long-term exercise and diet intervention on plasma adipokine concentrations. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults. Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes Absence of exercise-induced variations in adiponectin levels despite decreased abdominal adiposity and improved insulin sensitivity in type 2 diabetic men. Effect of statin and fibrate treatment on inflammation in type 2 diabetes. A randomized, cross-over study. Profibrinolytic, Antithrombotic, and Antiinflammatory Effects of an Insulin-Sensitizing Strategy in Patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
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 The relationship between insulin action and control of the adipocyte-derived factor adiponectin was studied in age- and weight-matched obese individuals with type 2 diabetes failing sulfonylurea therapy .  After initial metabolic characterization , subjects were r and omized to troglitazone or metformin treatment groups ; all subjects received glyburide ( 10 mg BID ) as well . Treatment was continued for 3 months . The extent of glycemic control after treatment was similar in both groups . However , the increase in maximal insulin-stimulated glucose disposal rate was greater following troglitazone therapy ( + 44 % ) compared with metformin treatment ( + 20 % ) . Troglitazone treatment increased serum adiponectin levels nearly threefold . There was no change in serum adiponectin with metformin treatment . A positive correlation was found between increases in whole-body glucose disposal rates and serum adiponectin levels after troglitazone ; no such relationship was seen with metformin . The adiponectin protein content of subcutaneous abdominal adipocytes was increased following troglitazone treatment and unchanged after metformin .  Adiponectin release from adipocytes was also augmented with troglitazone treatment . Adiponectin was present in adipocytes and plasma in several multimeric forms ; a trimer was the major form secreted from adipocytes . These results indicate that increases in adiponectin content and secretion are associated with improved insulin action but are not directly related to glycemic control . Modulation of adipocyte function , including upregulation of adiponectin synthesis and secretion , may be an important mechanism by which thiazolidinediones influence insulin action Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients . This protein possesses putative antiatherogenic and anti-inflammatory properties . In the current study , we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys ( Macaca mulatta ) , which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes . The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans . Prospect i ve longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes . Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake ( M rate ) . The plasma levels of adiponectin were significantly correlated to M rate ( r = 0.66 , P < 0.001 ) . Longitudinally , the plasma adiponectin decreased in parallel to the progression of insulin resistance . No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue . These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance OBJECTIVE ω-3 Polyunsaturated α-linolenic acid ( ALA ) supplementation has not been studied in the setting of adiponectin levels and insulin sensitivity ( IS ) improvements in patients with type 2 diabetes mellitus ( T2DM ) by hyperinsulinemic-euglycemic clamp ( HEC ) . The aim of this study was to examine the influence of ω-3 ALA on IS and adiponectin . METHODS We conducted a r and omized study in patients with T2DM and assessed IS using HEC . Twenty patients with T2DM were included and r and omly assigned to receive 3 g/d of ALA or placebo for 60 d , in a double-blind design . The assessment of IS by HEC was performed at baseline and after 60 d in all patients ; blood sample s were taken for the measurement of serum lipids , glucose , insulin , adiponectin , and cytokines . The primary outcome variables were an increase of both glucose infusion rate ( GIR ) in steady state and glucose metabolization ( M ) by HEC . The secondary outcomes were an increase in adiponectin levels and a decrease in fasting plasma glucose , glycated hemoglobin , homeostasis model assessment -estimated insulin resistance ( HOMA-IR ) index , lipids and cytokines . The study was conducted at an academic medical center . RESULTS The ALA group improved IS corrected for fat-free mass ( M/FFM ; P = 0.04 ) . Both groups showed increased adiponectin after 60 d ( P = 0.01 ) , however , the increase for the ALA group was greater ( P = 0.04 ) . In the ALA group , adiponectin was positively correlated with GIR ( r = 0.76 ; P = 0.01 ) and M/FFM ( r = 0.62 ; P = 0.06 ) , and negatively correlated with HOMA-IR ( r = -0.61 ; P = 0.03 ) . CONCLUSION ω-3 ALA supplementation improved glucose homeostasis and was associated with an increase in adiponectin . Improvement in the overall metabolic profile with ω-3 ALA suggests a potential clinical utility for this agent and requires further investigation Background : In observational studies , higher uric acid levels are associated with metabolic syndrome , diabetes , and kidney disease . Objective : The objective of this study is to examine whether reduction of plasma uric acid with febuxostat , a xanthine oxido reductase inhibitor , impacts adipose tissue oxidative stress , adipokines , and markers of systemic inflammation or kidney fibrosis . Design : This was a double-blinded r and omized controlled trial . Setting : Academic university setting was used . Patients : Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included . Measurements : Adipose tissue thiobarbituric acid reducing substances ( TBARS ) and adiponectin concentrations and urinary transforming growth factor – β ( TGF-β ) were primary endpoints . Plasma C-reactive protein , high molecular weight – adiponectin , interleukin–6 , tumor necrosis factor – α , and TBARS and albuminuria were among predefined secondary endpoints . Methods : Participants were r and omly assigned to febuxostat ( n = 40 ) or matching placebo ( n = 40 ) and followed for 24 weeks . Results : Baseline plasma uric acid levels were 426 ± 83 µmol/L ; 95 % completed the study . Estimated glomerular filtration rate ( eGFR ) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks ( P = .05 ) . In separate mixed-effects models , compared with placebo , febuxostat reduced uric acid by 50 % ( P < .001 ) but had no significant effects on subcutaneous adipose tissue TBARS ( −7.4 % , 95 % confidence interval [ CI ] , 57.4%-101.4 % ) or adiponectin ( 6.7 % , 95 % CI , 26.0%-53.8 % ) levels or urinary TGF-β/creatinine ratio ( 18.0 % , 95 % CI , 10.0%-54.8 % ) or secondary endpoints . Limitations : Relatively modest sample size and short duration of follow-up . Conclusions : In this population with progressive diabetic nephropathy  , febuxostat effectively reduced plasma uric acid . However , no detectable effects were observed for the prespecified primary or secondary endpoints . Trial Registration : The study was registered in clinical trials.gov ( NCT01350388 ) BACKGROUND Plasma adiponectin levels increase after the administration of glimepiride . This unique effects would also be expected to improve other adipocytokines and have anti-atherosclerotic action in patients with metabolic syndrome . METHODS Thirty-four patients with type 2 diabetes mellitus who were administrated glibenclamide  were r and omly divided into two groups . In 20 patients glibenclamide was changed to glimepiride ( GP group ) , and the administration of glibenclamide ( GB group ) was continued in 14 patients . Twelve patients receiving insulin therapy ( INS group ) were enrolled for comparison . The levels of plasma adiponectin , high sensitive-CRP , TNF-alpha , interleukin-6 , homeostasis model assessment -insulin resistance ( HOMA-IR ) , brachial-ankle pulse wave velocity ( baPWV ) and augmentation index ( AI ) were measured before and 28 weeks after the therapy . RESULTS HOMA-IR in the GP group was significantly decreased compared to the GB group . Plasma adiponectin levels were significantly increased in the GP group but not in the other groups . TNF-alpha , interleukin-6 and high sensitive-CRP levels were significantly decreased in the GP group , but not in the other groups . The baPWV and AI levels did not change in either the GB or the INS group , but were significantly decreased in the GP group . CONCLUSIONS Glimepiride appears to improve insulin resistance and atherosclerotic disorders BACKGROUND The lipid-lowering drug niacin has attracted renewed interest because it raises HDL-cholesterol and because it has recently been found to slow down the progression of intima media thickness in patients with coronary heart disease . Since niacin acts on adipocytes , we investigated its impact on adipokines and on some functions attributed to adipokines . METHODS AND RESULTS In a r and omized , placebo-controlled , double-blind study 30 men with the metabolic syndrome were treated for 6 weeks with 1500 mg extended-release niacin ( n=20 ) or a placebo ( n=10 ) . Adiponectin increased by 56 % ( p<0.001 ) and leptin by 26.8 % ( p<0.012 ) . Resistin , TNF-alpha , IL-6 , and high sensitive CRP remained unchanged . In spite of the increase in adiponectin there was no improvement in endothelial function . The HOMA index actually deteriorated by 42 % ( p<0.014 ) . CONCLUSION Short-term treatment with extended-release niacin causes a pronounced increase in adiponectin but fails to improve atheroprotective functions attributed to adiponectin , such as insulin sensitivity , anti-inflammation and endothelial function The insulin-sensitizing effects of thiazolidinediones are thought to be mediated through peroxisome proliferator-activated receptor-gamma , a nuclear receptor that is highly abundant in adipose tissue . It has been reported that adipocytes secrete a variety of proteins , including tumor necrosis factor-alpha , resistin , plasminogen activator inhibitor-1 , and adiponectin . Adiponectin is a fat cell-secreted protein that has been reported to increase fat oxidation and improve insulin sensitivity . Our aim was to study the effects of troglitazone on adiponectin levels in lean , obese , and diabetic subjects . Ten diabetic and 17 nondiabetic subjects ( 8 lean , BMI < 27 kg/m(2 ) and 9 obese , BMI > 27 kg/m(2 ) ) participated in the study . All subjects underwent an 80 mU. m(-2 ) . min(-1 ) hyperinsulinemic-euglycemic glucose clamp before and after 3 months ' treatment with the thiazolidinedione ( TZD ) troglitazone ( 600 mg/day ) . Fasting plasma glucose significantly decreased in the diabetic group after 12 weeks of treatment compared with baseline ( 9.1 + /- 0.9 vs. 11.1 + /- 0.9 mmol/l , P < 0.005 ) but was unchanged in the lean and obese subjects . Fasting insulin for the entire group was significantly lower than baseline ( P = 0.02 ) after treatment . At baseline , glucose disposal rate ( R(d ) ) was lower in the diabetic subjects ( 3.4 + /- 0.5 mg . kg(-1 ) . min(-1 ) ) than in the lean ( 12.3 + /- 0.4 ) or obese subjects ( 6.7 + /- 0.7 ) ( P < 0.001 for both ) and was significantly improved in the diabetic and obese groups ( P < 0.05 ) after treatment , and it remained unchanged in the lean subjects . Baseline adiponectin levels were significantly lower in the diabetic than the lean subjects ( 9.0 + /- 1.7 vs. 16.7 + /- 2.7 micro g/ml , P = 0.03 ) and rose uniformly in all subjects ( 12.2 + /- 2.3 vs. 25.7 + /- 2.6 micro g/ml , P < 10(-4 ) ) after treatment , with no significant difference detected among the three groups . During the glucose clamps , adiponectin levels were suppressed below basal levels in all groups ( 10.2 + /- 2.3 vs. 12.2 + /- 2.3 micro g/ml , P < 0.01 ) . Adiponectin levels correlated with R(d ) ( r = 0.46 , P = 0.016 ) and HDL cholesterol levels ( r = 0.59 , P < 0.001 ) and negatively correlated with fasting insulin ( r = -0.39 , P = 0.042 ) and plasma triglyceride ( r = -0.61 , P < 0.001 ) . Our findings show that TZD treatment increased adiponectin levels in all subjects , including normal subjects in which no other effects of TZDs are observed . Insulin also appears to suppress adiponectin levels . We have confirmed these results in normal rats . These findings suggest that adiponectin can be regulated by obesity , diabetes , TZDs , and insulin , and it may play a physiologic role in enhancing insulin sensitivity BACKGROUND In a r and omized , controlled , 2 x 2 factorial trial on the effect of long-term changes in diet and exercise , a significant reduction in body weight and fat mass was observed . Alterations in leptin and plasminogen activator inhibitor-1 concentrations were previously reported from this study . OBJECTIVE We examined the separate and combined effects of a 1-y exercise and diet intervention on several adipokines ; adiponectin , interleukin-6 and -8 , tumor necrosis factor-alpha , monocyte chemoattractant protein-1 , hepatocyte growth factor , nerve growth factor , C-reactive protein , and resistin . DESIGN One hundred eighty-eight men with several risk factors for diabetes and cardiovascular disease were r and omly allocated to 4 groups : diet , exercise , combined diet and exercise , and control . RESULTS Plasma adiponectin concentrations remained unchanged , whereas body mass index and fat mass decreased after dietary changes and an increase in physical activity . In the control group , adiponectin concentrations were reduced . Analyzed according to the factorial design , only diet intervention had a significant ( P = 0.03 ) positive effect on plasma adiponectin relative to control , and this effect was largely explained by changes in fat mass . After adjustment for change in percentage body fat , there were significant positive effects on tumor necrosis factor-alpha in all 3 intervention groups ( P = 0.01 for the diet group , 0.03 for the exercise group , and 0.05 for the combined diet and exercise group ) . Minor changes were observed for the other adipokines . Neither baseline concentrations of nor changes in adiponectin and plasminogen activator inhibitor-1 were significantly correlated to the other adipokines , whereas concentrations of and changes in the other adipokines were significantly correlated . CONCLUSION Diet intervention had a significant positive effect on adiponectin concentrations , which is largely explained by a reduction in fat mass Whereas thiazolidinediones ( TZDs ) are known to rapidly improve insulin action in animals , short duration s of TZD therapy have never been studied in humans . Among the many known actions of TZDs , increased circulating levels of the high molecular weight ( HMW ) multimer of adiponectin may be an important insulin-sensitizing mechanism . We examined the effects of only 21 days of 45 mg of pioglitazone ( P+ ) versus placebo ( P- ) in nine subjects with type 2 diabetes ( HbA(1c ) , 10.9 + /- 0.6 % ; BMI , 31.9 + /- 1.5 kg/m(2 ) ) .  Total adiponectin levels increased by approximately twofold in P+ in association with increased adipose tissue gene expression . However , plasma free fatty acid and glucose levels were unchanged , and there were only minimal changes in other " adipokines . " Glucose fluxes ( [3-(3)H]glucose infusion ) were measured during 6-h euglycemic ( 5 mmol/l ) " pancreatic clamp " studies ( somatostatin/glucagon/growth hormone ) with stepped insulin levels . Pioglitazone induced marked decreases in endogenous glucose production ( P+ = 0.9 + /- 0.1 vs. P- = 1.7 + /- 0.3 mg . kg(-1 ) . min(-1 ) ; P < 0.05 ) at physiologic hyperinsulinemia ( approximately 50 microU/ml ) , which was highly correlated with an increased ratio of HMW adiponectin/total levels ( r(2 ) = 0.90 ) . Maximal insulin stimulation ( approximately 400 microU/ml ) revealed pioglitazone-associated increases in glucose uptake ( P+ = 10.5 + /- 0.9 vs. P- = 8.9 + /- 0.8 mg . kg(-1 ) . min(-1 ) ; P < 0.05 ) , which did not correlate with HMW or total adiponectin levels . Thus , only 21 days of pioglitazone therapy improved insulin action in humans with type 2 diabetes . Increased abundance of the HMW adiponectin multimer may contribute to the hepatic insulin-sensitizing effects of these agents OBJECTIVES Gonadotropin-releasing hormone agonists increase fat mass , decrease insulin sensitivity , and increase serum triglycerides . To better characterize the metabolic effects of gonadotropin-releasing hormone agonist treatment , we prospect ively evaluated the changes in body composition , insulin sensitivity , and levels of adiponectin , resistin , C-reactive protein ( CRP ) , and plasminogen activator inhibitor type 1 ( PAI-1 ) . We also assessed the relationships among changes in adipocytokines , body composition , and insulin sensitivity . METHODS In this prospect i ve , 12-week study , 25 nondiabetic men with locally advanced or recurrent prostate cancer and no radiographic evidence of metastases were treated with leuprolide depot and bicalutamide . The outcomes studied included changes from baseline to week 12 in body composition , insulin sensitivity , and levels of adiponectin , resistin , CRP , and PAI-1 . RESULTS The mean + /- st and ard error percentage of fat body mass increased by 4.3 % + /- 1.3 % from baseline to week 12 ( P = 0.002 ) . The insulin sensitivity index decreased by 12.9 % + /- 7.6 % ( P = 0.02 ) . The serum adiponectin levels increased by 37.4 % + /- 7.2 % from baseline to week 12 ( P < 0.001 ) . In contrast , the resistin , CRP , and PAI-1 levels did not change significantly . Changes in body composition tended to be associated with changes in adiponectin , but not insulin sensitivity . CONCLUSIONS Combined and rogen blockade with leuprolide and bicalutamide significantly increased fat mass and adiponectin levels and decreased insulin sensitivity but did not alter the resistin , CRP , or PAI-1 levels . This pattern of metabolic changes appears distinct from the classic metabolic syndrome Adiponectin , the most abundant adipose-specific protein , has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other population s. Moreover , adiponectin administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor ( IR ) and also increase whole-body insulin sensitivity . To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans , we examined 1 ) the cross-sectional association between plasma adiponectin concentration and skeletal muscle IR tyrosine phosphorylation and 2 ) the prospect i ve effect of plasma adiponectin concentration at baseline on change in insulin sensitivity . Fasting plasma adiponectin concentration , body composition ( hydrodensitometry or dual energy X-ray absorptiometry ) , insulin sensitivity ( insulin-stimulated glucose disposal , hyperinsulinemic clamp ) , and glucose tolerance ( 75-g oral glucose tolerance test ) were measured in 55 Pima Indians ( 47 men and 8 women , aged 31 + /- 8 years , body fat 29 + /- 8 % [ mean + /- SD ] ; 50 with normal glucose tolerance , 3 with impaired glucose tolerance , and 2 with diabetes ) . Group 1 ( 19 subjects ) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR ( stimulated by 100 nmol/l insulin ) . The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation . Group 2 ( 38 subjects ) had follow-up measurements of insulin-stimulated glucose disposal .  Cross-sectionally , plasma adiponectin concentration was positively associated with insulin-stimulated glucose disposal ( r = 0.58 , P < 0.0001 ) and negatively associated with percent body fat ( r = -0.62 , P < 0.0001 ) in the whole group . In group 1 plasma adiponectin was negatively associated with the basal ( r = -0.65 , P = 0.003 ) and positively associated with the fold increase in IR tyrosine phosphorylation ( r = 0.69 , P = 0.001 ) before and after the adjustment for percent body fat ( r = -0.58 , P = 0.01 and r = 0.54 , P = 0.02 , respectively ) . Longitudinally , after adjustment for age , sex , and percent body fat , low plasma adiponectin concentration at baseline was associated with a decrease in insulin sensitivity ( P = 0.04 ) . In conclusion , our cross-sectional data suggest a role of physiological concentration of fasting plasma adiponectin in the regulation of skeletal muscle IR tyrosine phosphorylation . Prospect ively , low plasma adiponectin concentration at baseline precedes a decrease in insulin sensitivity . Our data indicate that adiponectin plays an important role in regulation of insulin sensitivity in humans Circulating adiponectin is reduced in disorders associated with insulin resistance . This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle . Impaired glucose-tolerant older ( > 60 yr ) obese ( BMI 30 - 40 kg/m(2 ) ) men ( n = 7 ) and women ( n = 14 ) were r and omly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric ( ExHypo , approximately 500 kcal reduction , n = 11 ) or eucaloric diet ( ExEu , n = 10 ) . Insulin sensitivity was determined by the euglycemic ( 5.0 mM ) hyperinsulinemic ( 40 mU x m(-2 ) x min(-1 ) ) clamp . Adiponectin multimers [ high ( HMW ) , middle ( MMW ) , and low molecular weight ( LMW ) ] were measured by nondenaturing Western blot analysis . Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy sample s. Greater weight loss occurred in ExHypo compared with ExEu subjects ( 8.0 + /- 0.6 vs. 3.2 + /- 0.6 % , P < 0.0001 ) . Insulin sensitivity improved postintervention in both groups ( ExHypo : 2.5 + /- 0.3 vs. 4.4 + /- 0.5 mg x kg FFM(-1 ) x min(-1 ) , and ExEu : 2.9 + /- 0.4 vs. 4.1 + /- 0.4 mg x kg FFM(-1 ) x min(-1 ) , P < 0.0001 ) . Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW ( P < 0.03 ) . The adiponectin SA ratio ( HMW/total ) was increased following both interventions ( P < 0.05 ) and correlated with the percent change in insulin sensitivity ( P < 0.03 ) . Postintervention adiponectin receptor mRNA expression was also significantly increased ( AdipoR1 P < 0.03 , AdipoR2 P < 0.02 ) . These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression Aims /hypothesisAdipokines may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature . We studied the effect of different glucose-lowering therapies on serum levels of plasminogen activator inhibitor-1 ( PAI-1 ) , high-sensitivity C-reactive protein ( hs-CRP ) , TNF-α , leptin , adiponectin and ghrelin in patients with type 2 diabetes . Subjects and methods Twenty-eight patients with poorly controlled type 2 diabetes who were receiving oral hypoglycaemic agents  were allocated to one of the following groups , and treated for 1 year : ( 1 ) lifestyle intervention ( L ) ; ( 2 ) insulin treatment ( I ) ; and ( 3 ) combined treatment ( L+I ) . Results Similar improvements in glycaemic control occurred in all three groups . There was a reduction in body weight of 3.0 kg ( median ) ( 95 % CI −5.9 to −2.0 ) in group L , whereas in groups L+I and I body weight increased by 3.5 kg ( 95 % CI 1.5–4.9 ) and 4.9 kg ( 95 % CI −3.1 to 8.2 ) , respectively . By trend analyses , group L had reduced levels of PAI-1 ( p=0.002 ) , hs-CRP ( p<0.0001 ) and TNF-α ( p=0.006 ) , while no significant changes were observed in the levels of leptin or adiponectin . In group I , the median levels of PAI-1 ( p=0.008 ) , TNF-α ( p=0.058 ) and leptin ( p=0.004 ) increased . In the L+I group there was a reduction in PAI-1 levels ( p=0.014 ) and an increase in levels of leptin ( p<0.001 ) . The differences in changes in the levels of PAI-1 , hs-CRP , TNF-α and leptin between groups were also significant ( all p<0.01 ) . Conclusions /interpretationImprovement of glycaemic control through lifestyle intervention in type 2 diabetes had more beneficial effects on adipokine levels than when the same lowering of HbA1c was achieved with insulin treatment OBJECTIVE We investigated the effect of an intensive training program on fasting leptin and adiponectin levels . METHODS Sixteen middle-aged men with type 2 diabetes were r and omly assigned to either a training or control group . The training program consisted of 8 weeks of supervised endurance exercise ( 75 % VO(2peak ) , 45 min ) twice a week , with intermittent exercise ( five 2 min exercises at 85 % VO(2peak ) separated by 3 min exercises at 50 % VO(2peak ) ) once a week , on an ergocycle . RESULTS Training decreased abdominal fat by 44 % , increased mid-thigh muscle cross-sectional area by 24 % , and improved insulin sensitivity by 58 % without significant change in body weight . Compared with controls , no significant variation in leptin or adiponectin levels was observed . However , in the trained group , change in adiponectin correlated with change in body weight ( Spearman rank correlation , r(s):-0.76 , P=0.03 ) but not with insulin sensitivity or abdominal adiposity variations . CONCLUSIONS An 8 week intensive training program inducing a marked reduction in abdominal fat and increase in insulin sensitivity does not affect adiponectin and leptin levels in men with type 2 diabetes A r and omized , crossover study compared the effects of atorvastatin , gemfibrozil and their combination on inflammatory markers in type 2 diabetes .  C-reactive protein ( CRP ) , lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , secretory phospholipase A2 ( sPLA2 ) , interleukin 8 ( IL8 ) , monocyte chemotactic protein 1 ( MCP1 ) and tumor necrosis factor α ( TNFα ) were measured . Both lipid-lowering drugs had positive , complementary and additive effects on inflammatory markers , which were closely related to baseline inflammatory status Background — Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes ( BARI 2D ) trial of 2 mechanistically different strategies for treatment of hyperglycemia , insulin-sensitizing and insulin-providing strategies , on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy . Methods and Results — A total of 2368 patients with type 2 diabetes mellitus and clinical ly stable , angiographically documented coronary artery disease were r and omized to treatment with 1 of the 2 strategies and followed for an average of 5 years . Plasminogen activator inhibitor type 1 antigen and activity , tissue plasminogen activator antigen , fibrinogen , D-dimer , C-reactive protein , insulin , and hemoglobin A1c were assayed in blood sample s acquired at baseline and at 12 regular intervals throughout the follow-up interval . Higher baseline D-dimer , fibrinogen , and C-reactive protein portended a poor prognosis in patients in both groups . In contrast to the insulin-providing strategy , the insulin-sensitizing strategy led to ( 1 ) lower plasma insulin ; ( 2 ) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen ( known to track with plasminogen activator inhibitor type 1 ) ; and ( 3 ) lower C-reactive protein and fibrinogen at all intervals after baseline ( P<0.001 for each ) . Conclusions — The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance , an altered balance between thrombosis and fibrinolysis favoring fibrinolysis , and diminished intensity of the systemic inflammatory state , factors that have been associated with cardiovascular risk . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00006305
The observed effect was robust in sensitivity analyses and independent of fibrate dose .
The present meta- analysis suggests that fibrate therapy increases circulating levels of adiponectin .
BACKGROUND Several lines of evidence have indicated the insulin-sensitizing , anti-diabetic and anti-atherosclerotic properties of adiponectin , as well as the inverse association between circulating levels of this adipokine and development of cardiovascular outcomes .
Improvement of adiponectin status has been reported as a pleiotropic effect of fibrate therapy , but the findings have not been conclusive .
OBJECTIVE To systematic ally review and meta-analyze available evidence from r and omized placebo-controlled trials ( RCTs ) on the impact of fibrate therapy on circulating levels of adiponectin .