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. Effects of n-3 polyunsaturated fatty acids (PUFAs) on circulating adiponectin and leptin in subjects with type 2 diabetes mellitus. Periodontal treatment with topical antibiotics improves glycemic control in association with elevated serum adiponectin in patients with type 2 diabetes mellitus. Beneficial effects of n-3 polyunsaturated fatty acids on adiponectin levels and AdipoR gene expression in patients with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blind clinical trial Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial. Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects. Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis. Incidence of diabetes and serum adipokines in Catalonian men. The ADIPOCAT study Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes Effects of n-3 fatty acids and exercise on oxidative stress parameters in type 2 diabetic: a randomized clinical trial n-3 polyunsaturated fatty acids and adiponectin in patients with end-stage renal disease. Lifestyle Intervention and Adipokine Levels in Subjects at High Risk for Type 2 Diabetes Prediagnostic Leptin, Adiponectin, C-Reactive Protein, and the Risk of Postmenopausal Breast Cancer Telmisartan reduced blood pressure and HOMA-IR with increasing plasma leptin level in hypertensive and type 2 diabetic patients. Creation of a database to assess effects of omega-3, omega-6 and total polyunsaturated fats on health: methodology for a set of systematic reviews Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial. Clinical Significance of Serum Adipokines according to Body Mass Index in Patients with Clinically Localized Prostate Cancer Undergoing Radical Prostatectomy Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study Circulating adipokines and mRNA expression in adipose tissue and the placenta in women with gestational diabetes mellitus Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial. Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial.
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 Recent evidence suggests that omega-3 polyunsaturated fatty acids [ n-3 PUFAs : eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ] , improve insulin sensitivity in humans . In a double-blind , placebo-controlled , r and omized , crossover study , we investigated the effects of EPA/DHA on paraoxonase-1 activity as well as fasting and postpr and ial levels of circulating adiponectin and leptin in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks either 2 g purified EPA/DHA or olive oil ( placebo ) , separated by a 6 weeks washout . At the end of each treatment , measurements were performed in fasting state and 2 , 4 , and 6 h following a st and ardized high-fat meal ( 600 kcal ) . No significant differences in fasting and postpr and ial circulating adiponectin , leptin , and paraoxonase-1 activity were seen between n-3 PUFAs and placebo . Our data do not support an insulin sensitizing effect of n-3 PUFAs by means of influencing circulating adipocytokines in this population . Clinical Trial Register Number : NCT00328536 OBJECTIVES Chronic inflammation of periodontitis aggravates glycemic control in type 2 diabetic patients through aggravation of insulin resistance . Increased or decreased release of various inflammatory mediators , such as high sensitivity C-reactive protein ( hs-CRP ) , tumor necrosis factor (TNF)-α , interleukin (IL)-6 and adipokines , such as adiponectin , leptin , and resistin , are presumed to be responsible for developing and progressing insulin resistance . The purpose of this study was to examine the effects of periodontal treatment on glycemic control , serum inflammatory mediators and adipokines in type 2 diabetes patients with periodontitis . METHODS Twenty-one type 2 diabetic patients with periodontitis received periodontal treatment with topical antibiotics ( intervention group ) and 8 patients did not receive periodontal treatment ( control group )  . Periodontal examination , including probing pocket depth ( PPD ) and bleeding on probing ( BOP ) , and blood sampling  were performed at baseline , 2 and 6 months after periodontal treatments . Glycated hemoglobin ( HbA1c ) , hs-CRP , TNF-α , IL-6 , adiponectin , leptin , and resistin were analyzed . RESULTS In the intervention group , improvements of PPD and BOP , decrease in HbA1c and elevation of serum adiponectin were observed , while in the control group , all parameters were not changed . Generalized linear model revealed that changes of serum adiponectin and TNF-α and change of BOP correlated significantly with the reduction of HbA1c at 6 months after periodontal treatments . CONCLUSION The results demonstrated that periodontal treatment improves periodontal status and glycemic control with elevation of serum adiponectin in type 2 diabetic patients . The results suggest that HbA1c is reduced by amelioration of insulin resistance due to elevated serum adiponectin after periodontal treatments Introduction There is evidence that n-3 polyunsaturated fatty acids ( n-3 PUFAs ) exert beneficial effects to improve type 2 diabetes mellitus ( T2DM ) , but its complications remain poorly understood . Hypoadiponectinemia is one of the important mechanisms responsible for T2DM which necessitates developing novel therapeutic strategies . We aim ed to determine the effect of n-3 PUFA supplementation on circulating adiponectin and mRNA expression of adiponectin receptors ( AdipoR1 , AdipoR2 ) and Sirt-1 in T2DM patients . Material and methods A r and omized , double-blind , placebo-controlled trial of 10-week follow-up of n-3 PUFAs ( 2.7 g/day ) vs. placebo in T2DM patients ( n = 88 ) was conducted . In detail , T2DM patients ( n = 44 ) were treated with n-3 PUFAs and the remainder received placebo .  Anthropometric and metabolic characteristics were assessed in all participants .  Circulating level of adiponectin and mRNA expression of AdipoR1 , AdipoR2 and Sirt-1 were measured in peripheral blood mononuclear cells ( P BMC ) using real-time polymerase chain reaction before and after the intervention . Results It was found that n-3 PUFAs  increased AdipoR1 gene expression ( fold change = 1.321 in n-3 PUFAs vs. 1.037 in placebo ) and AdipoR2 mRNA ( fold change = 1.338 in n-3 PUFAs vs. 1.034 in placebo ) . No significant changes were observed for Sirt-1 expression . The serum level of adiponectin significantly ( p = 0.035 ) increased in n-3 PUFAs ( 5.09 to 5.58 μg/ml ) but remained unchanged in the placebo group . Conclusions Daily supplementation with n-3 PUFAs ( 2.7 g ) was effective to significantly improve gene expression of AdipoR1 and AdipoR2 and the serum level of adiponectin in T2DM patients . Therefore , n-3 PUFAs might emerge as an adjuvant for current antidiabetic therapies . However , confirmatory long-term studies are required OBJECTIVE Offspring of patients with type 2 diabetes ( OPDs ) exhibits endothelial dysfunction ( ED ) associated with a chronic inflammatory state . N-3 polyunsaturated fatty acids ( n-3 PUFA ) may have antioxidant and anti-inflammatory properties that are beneficial for cardiovascular and metabolic health . Therefore , in the present study , we tested the hypothesis that dietary supplementation with fish oil rich in n-3 PUFA may improve ED in otherwise healthy OPDs . METHODS AND DESIGN A double-blind , placebo-controlled trial was conducted with 50 OPDs . Participants were r and omized to treatment with either placebo or n-3 PUFA ( 2g/day ) for 12 weeks . Before and after treatment we evaluated endothelial function ( using flow-mediated dilation ( FMD ) of the brachial artery ) , circulating inflammatory markers ( adiponectin , TNF-alpha , and high sensitivity-CRP ) , and insulin resistance ( QUICKI ) . RESULTS No significant changes were observed in study outcomes in subjects treated with placebo . By contrast , when compared with baseline values , subjects treated with n-3 PUFA had significant improvement in FMD ( 9.1+/-5.8 % vs. 11.7+/-4.4 % , p=0.02 ) that was accompanied by decreased plasma triglycerides ( 117+/-73mg/dl vs. 86+/-44mg/dl , p=0.001 ) and TNF-alpha levels ( 8.9+/-2.3pg/ml vs. 6.8+/-2.7pg/ml , p=0.001 ) , and a trend towards increased plasma adiponectin levels ( 7.8+/-4.5microg/ml vs. 9.5+/-5.1microg/ml , p=0.09 ) . When data were analyzed by multiple regression analysis , decreased TNF-alpha after treatment with n-3 PUFA predicted increased FMD . CONCLUSION Dietary supplementation with n-3 PUFA significantly improved endothelial function and reduced pro-inflammatory markers in OPDs . Thus , fish oil consumption may have beneficial cardiovascular and metabolic health effects in otherwise healthy subjects predisposed to diabetes and its vascular complications BACKGROUND Information is lacking on the potential effect of n-3 polyunsaturated fatty acids ( PUFAs ) on the adipose tissue of patients with type 2 diabetes . OBJECTIVE We evaluated whether n-3 PUFAs have additional effects on adiposity , insulin sensitivity , adipose tissue function ( production of adipokines and inflammatory and atherogenic factors ) , and gene expression in type 2 diabetes . DESIGN Twenty-seven women with type 2 diabetes without hypertriglyceridemia were r and omly allocated in a double-blind parallel design to 2 mo of 3 g/d of either fish oil ( 1.8 g n-3 PUFAs ) or placebo ( paraffin oil ) . RESULTS Although body weight and energy intake measured by use of a food diary were unchanged , total fat mass ( P < 0.019 ) and subcutaneous adipocyte diameter ( P < 0.0018 ) were lower in the fish oil group than in the placebo group . Insulin sensitivity was not significantly different between the 2 groups ( measured by homeostasis model assessment in all patients and by euglycemic-hyperinsulinemic clamp in a subgroup of 5 patients per group ) . By contrast , atherogenic risk factors , including plasma triacylglycerol ( P < 0.03 ) , the ratio of triacylglycerol to HDL cholesterol ( atherogenic index , P < 0.03 ) , and plasma plasminogen activator inhibitor-1 ( P < 0.01 ) , were lower in the fish oil group than in the placebo group . In addition , a subset of inflammation-related genes was reduced in subcutaneous adipose tissue after the fish oil , but not the placebo , treatment . CONCLUSIONS A moderate dose of n-3 PUFAs for 2 mo reduced adiposity and atherogenic markers without deterioration of insulin sensitivity in subjects with type 2 diabetes . Some adipose tissue inflammation-related genes were also reduced . These beneficial effects could be linked to morphologic and inflammatory changes in adipose tissue . This trial was registered at clinical trials.gov as NCT0037 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 Obesity is associated with an increased risk of cardiovascular disease , whereas long-chain n-3 polyunsaturated fatty acids ( PUFAs ) from fish may have cardioprotective and anti-inflammatory effects . This study aim ed to investigate the hypothesis that acute and short-term supplementation with a low dose of marine n-3 PUFA exerts an anti-inflammatory effect in overweight subjects . In a double-blind , placebo-controlled trial with 2 parallel groups , 50 overweight subjects were r and omized to receive daily supplementation with 2 capsules containing either 2 g of fish oil ( 1.1 g marine n-3 PUFA ) or 2 g of olive oil .  Blood sample s and adipose tissue biopsies were collected at baseline , after 1 day ( acute effect ) , and after 6 weeks ( short-term effect ) of supplementation . No significant effects were seen after supplementation for 1 day , but after 6 weeks , subjects receiving fish oil had a significant increase in the n-3 PUFA content of granulocytes and adipose tissue ( P < .01 ) . Serum adiponectin levels were increased by 0.55 μg/mL ( 95 % confidence interval , 0.02 - 1.08 ) in the fish oil group compared with the control group ( P = .04 ) after 6 weeks of supplementation . Levels of interleukin 6 were inversely correlated to the marine n-3 PUFA content of granulocytes and adipose tissue at baseline ( excluding α-linolenic acid ) . In conclusion , daily supplementation with 1.1 g of marine n-3 PUFA  significantly increased serum adiponectin , but the effect was small , and no overall anti-inflammatory effect of the supplement could be demonstrated AIM To examine whether poly-unsaturated fatty acid ( PUFA ) therapy is beneficial for improving  nonalcoholic steatohepatitis ( NASH ) . METHODS In total , 78 patients pathologically diagnosed with NASH were enrolled and were r and omly assigned into the control group and the PUFA therapy group ( added 50 mL PUFA with 1:1 ratio of EHA and DHA into daily diet ) . At the initial analysis and after 6 mo of PUFA therapy , parameters of interest including liver enzymes , lipid profiles , markers of inflammation and oxidation , and histological changes were evaluated and compared between these two groups . RESULTS At the initial analysis , in patients with NASH , serum levels of alanine aminotransferase ( ALT ) and aspartase aminotransferase ( AST ) were slightly elevated . Triglyceride ( TG ) , total cholesterol ( TC ) and low-density lipoprotein cholesterol levels , markers of systemic inflammation [ C-reactive protein ( CRP ) ] and oxidation [ malondialdehyde ( MDA ) ] , as well as fibrosis parameters of type IV collagen and pro-collagen type III pro-peptide were also increased beyond the normal range . Six months later , ALT and AST levels were significantly reduced in the PUFA group compared with the control group . In addition , serum levels of TG and TC , CRP and MDA , and type IV collagen and pro-collagen type III pro-peptide were also simultaneously and significantly reduced . Of note , histological evaluation showed that steatosis grade , necro-inflammatory grade , fibrosis stage , and ballooning score were all profoundly improved in comparison to the control group , strongly suggesting that increased PUFA consumption was a potential way to offset NASH progression . CONCLUSION Increased PUFA consumption is a potential promising approach for NASH prevention and reversal Aims . To investigate the relationship of body mass index and serum adipokines with  incidence of diabetes in men . Material and methods . Ten-year cohort study of a r and om population sample of 1011 men aged 35–69 years from the MONICA-Catalonia survey ( 1986–1988 ) . WHO-MONICA protocol and the US Hispanic NHANES diabetes question naire were applied .  Fasting serum glucose and lipids were measured by enzymatic methods , adipokines and insulin by Luminex xMAP technology , and hs-CRP by nephelometry in stored baseline sample s ( –80 ° C ) . Type2 diabetes was defined as fasting glucose ≥ 7.0 mmol/L or diagnosed diabetes . Incident diabetes was defined as absence of these criteria at baseline but presence at re-examination . Cox regression analysis was used . Results . Incidence of diabetes ( n = 85 ) was 10.3/1000 person-years , increasing significantly with BMI but decreasing by quartiles of adiponectin . Incidence increased above median BMI and glucose ( 45.3/1000 person-years , OR = 19.97 ) . Log-adiponectin associated with reduced risk of diabetes after multivariate adjustment ( HR = 0.24 , 95 % CI 0.08–0.72 ) , with significant modification of this effect by baseline glycaemia . C-reactive protein was not a significant factor . Leptin lost strength when adjusted for BMI . Conclusions . In a population with relatively high diabetes incidence , BMI and glucose were strong risk factors , while adiponectin protected against diabetes , especially in men with high glycaemic level 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 Background The relationship between diabetes and oxidative stress has been previously reported . Exercise represents a useful non-pharmacological strategy for the treatment in type 2 diabetic ( T2DM ) patients , but high intensity exercise can induce a transient inflammatory state and increase oxidative stress . Nutritional strategies that may contribute to the reduction of oxidative stress induced by acute exercise are necessary . The aim of this study was to examine if n-3 PUFA supplementation intervention can attenuate the inflammatory response and oxidative stress associated with high intensity exercise in this population . As a primary outcome , lipoperoxidation measurements ( TBARS and F2-isoprostanes ) were selected . Methods Thirty T2DM patients , without chronic complications , were r and omly allocated into two groups : placebo ( gelatin capsules ) or n-3 PUFA ( capsules containing 180 mg of eicosapentaenoic acid and 120 mg of docosahexaenoic acid ) . Blood sample s were collected fasting before and after 8 weeks supplementation . In the beginning and at the end of protocol , an acute exercise was performed ( treadmill ) , and new blood sample s were collected before and immediately after the exercise for measurements of oxidative stress and high-sensitivity C-reactive protein ( hs-CRP ) . Results After the supplementation period , a decrease in triglycerides levels was observed only in n-3 PUFA supplementation group ( mean difference and 95 % CI of 0.002 ( 0.000–0.004 ) , p = 0.005 ) . Supplementation also significantly reduced TRAP levels after exercise ( mean difference and 95 % CI to 9641 ( − 20,068–39,351 ) for − 33,884 ( − 56,976 - -10,793 ) , p = 0.004 , Cohen ’s d effect size = 1.12 ) , but no significant difference was observed in n-3 PUFA supplementation group in lipoperoxidation parameters as TBARS ( mean difference and 95 % CI to − 3.8 ( − 10–2.4 ) for − 2.9 ( − 1.6–7.4 ) or F2-isoprostanes ( mean difference and 95 % CI -0.05 ( − 0.19–0.10 ) for − 0.02 ( − 0.19–0.16 ) , p > 0.05 for both . Conclusion PUFA n-3 supplementation  reduced triglycerides as well as TRAP levels after exercise , without a significant effect on inflammatory and oxidative stress markers . This study is registered at Clinical Trials.gov with the registration number of NCT03182712 BACKGROUND AND AIM In subjects without kidney disease , adiponectin appears to have anti-inflammatory , anti-diabetic , and anti-atherogenic effects . n-3 polyunsaturated fatty acids ( PUFA ) from seafood have several beneficial effects in patients with endstage renal disease ( ESRD ) and the aim of the present study was to assess the effect of n-3 PUFA supplementation on plasma adiponectin levels in ESRD patients . METHODS In a double blinded intervention trial , 162 ESRD patients ( mean age 67 years Â ± 13 , 56 women and 106 men ) undergoing chronic hemodialysis were r and omized to 1.7 g n-3 PUFA daily or placebo for 3 months . Adiponectin , plasma lipids and lipoproteins were measured at baseline and after the intervention period . RESULTS At baseline , adiponectin was positively correlated to HDL-cholesterol ( r = 0.55 , p < 0.001 ) and inversely correlated to plasma triglycerides , body mass index ( BMI ) and high sensitive C-reactive protein ( Hs-CRP ) ( r = -0.32 , p < 0.01 , r = -0.43 , p < 0.01 , and r = -0.21 , p < 0.01 , respectively ) . Furthermore , adiponectin was inversely correlated to the plasma levels of the two major n-3 PUFA docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) ( r = -0.19 , p < 0.001 , and r = -0.30 , p < 0.001 , respectively ) . Baseline plasma adiponectin levels were high in both groups but after 3 months of supplementation no significant change was observed in the groups . Thus , n-3 PUFA supplementation did not change adiponectin levels . CONCLUSION We found an elevated plasma adiponectin level , which was inversely associated with plasma levels of DHA and EPA at baseline . Supplementation with n-3 PUFAs for 3 months did not change adiponectin levels . The negative result in this study may be related to a relatively low dose and future studies with higher dose and longer duration are needed to explore this mechanism 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 Obesity has been associated with an increased risk of postmenopausal breast cancer . Adipokines and systemic inflammation have been hypothesized to underlie this association . In a case – control study nested within the Multiethnic Cohort , conditional logistic regression was used to calculate the ORs and 95 % confidence intervals ( CI ) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin , adiponectin , the leptin : adiponectin ratio , and C-reactive protein ( CRP ) . The 706 cases and 706 controls were matched on ethnicity , location ( Hawaii or Los Angeles ) , birth year , date and time of blood draw , hours fasting before blood draw , and hormone replacement therapy use at blood draw . Higher circulating levels of leptin [ ORQ4 vs. Q1 , 1.94 ( 1.37–2.75 ) ; Ptrend ≤ 0.001 ) , the leptin : adiponectin ratio [ OR , 1.91 ( 1.36–2.68 ) ; Ptrend = 0.005 ] , and CRP [ OR , 1.41 ( 1.01–1.96 ) ; Ptrend = 0.014 ] were associated with an increased risk of postmenopausal breast cancer . The positive associations for these markers remained after adjustment for body mass index ( BMI ) . No associations were detected for adiponectin . These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI . Further prospect i ve studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted . Cancer Prev Res ; 6(3 ) ; 188–95 . © 2013 AACR Telmisartan , a new angiotensin II type 1 receptor blocker ( ARB ) , was recently reported to stimulate PPARgamma , and stronger effects of Telmisartan on insulin sensitivity has been expected than the class effect of ARB . In the present study , we examined the effects of Telmisartan on insulin sensitivity and adipokine levels in hypertensive and type 2 diabetic patients . Out patients with both hypertension and type 2 diabetes mellitus ( n=36 ; male 23 , female 13 ) , received 20 - 40 mg Telmisartan orally once daily for 6 months . Physical examinations and blood or urine tests were performed before and 3 or 6 months after starting Telmisartan treatment . Results were statistically compared using Wilcoxon analysis . Telmisartan treatment for 3 or 6 months reduced systolic and diastolic blood pressure and urinary albumin excretion . Fasting plasma glucose , HbA1c , total and HDL-cholesterol , triglyceride , body weight , BMI and waist length were not changed . Fasting IRI and HOMA-IR were significantly decreased after Telmisartan treatment , suggesting the improved insulin sensitivity . Total and high molecular adiponectin were not changed . Interestingly , serum leptin was significantly increased by 3 months Telmisartan treatment , suggesting a possible involvement of leptin in improved insulin sensitivity . In conclusion , Telmisartan improved insulin resistance with increased serum leptin level in hypertensive and type 2 diabetic patients Objective To create a data base of long-term r and omised controlled trials ( RCTs ) comparing higher with lower omega-3 , omega-6 or total polyunsaturated fatty acid ( PUFA ) , regardless of reported outcomes , and to develop methods to assess effects of increasing omega-6 , alpha-linolenic acid ( ALA ) , long-chain omega-3 ( LCn3 ) and total PUFA on health outcomes . Design Systematic review search , methodology and meta-analyses . Data sources Medline , Embase , CENTRAL , WHO International Clinical Trials Registry Platform , Clinical trials.gov and trials in relevant systematic review s. Eligibility criteria RCTs of ≥24 weeks ' duration assessing effects of increasing ALA , LCn3 , omega-6 or total PUFAs , regardless of outcomes reported . Data synthesis Methods included r and om-effects meta-analyses and sensitivity analyses . Funnel plots were examined , and subgrouping assessed effects of intervention type , replacement , baseline diabetes risk and use of diabetic medications , trial duration and dose . Quality of evidence was assessed using Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) . Results Electronic search es generated 37 810 hits , de-duplicated to 19 772 titles and abstract s. We assessed 2155 full-text papers , conference abstract s and trials registry entries independently in duplicate . Included studies were grouped into 363 RCTs comparing higher with lower omega-3 , omega-6 and /or total PUFA intake of at least 6 months ’ duration —the Data base . Of these 363 included RCTs , 216 RCTs were included in at least one of our review s of health outcomes , data extracted and risk of bias assessed in duplicate . Ninety five RCTs were included in the Data base but not included in our current review s. Of these 311 completed trials , 27 altered ALA intake , 221 altered LCn3 intake and 16 trials altered omega-3 intake without specifying whether ALA or LCn3 . Forty one trials altered omega-6 and 59 total PUFA.The remaining 52 trials are ongoing though 13 ( 25 % ) appear to be outst and ing , or constitute missing data . Conclusions This extensive data base of trials is available to allow assessment of further health outcomes Observational studies have suggested that 25-hydroxyvitamin D ( 25(OH)D ) levels are associated with inflammatory markers . Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups . Thus , we aim ed to determine the effect of supplementary vitamin D using secondary data from a population -based , r and omised , placebo-controlled , double-blind trial ( Pilot D-Health trial 2010/0423 ) . Participants were 60- to 84-year-old residents of one of the four eastern states of Australia . They were r and omly selected from the electoral roll and were r and omised to one of three trial arms : placebo ( n 214 ) , 750 μg ( n 215 ) or 1500 μg ( n 215 ) vitamin D3 , each taken once per month for 12 months . Post-intervention blood sample s for the analysis of C-reactive protein ( CRP ) , IL-6 , IL-10 , leptin and adiponectin levels were available for 613 participants . Associations between intervention group and biomarker levels were evaluated using quantile regression . There were no statistically significant differences in distributions of CRP , leptin , adiponectin , leptin : adiponectin ratio or IL-10 levels between the placebo group and either supplemented group . The 75th percentile IL-6 level was 2·8 pg/ml higher ( 95 % CI 0·4 , 5·8 pg/ml ) in the 1500 μg group than in the placebo group ( 75th percentiles:11·0 v. 8·2 pg/ml ) , with a somewhat smaller , non-significant difference in 75th percentiles between the 750 μg and placebo groups . Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation , we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels , with the possible exception of IL-6 Purpose The aim of this study was to investigate the clinical significance of 7 circulating adipokines according to body mass index ( BMI ) in Korean men with localized prostate cancer ( PCa ) undergoing radical prostatectomy ( RP ) .  Material s and Methods Sixty-two of 65 prospect ively enrolled patients with clinical ly localized PCa who underwent RP between 2015 and 2016 were evaluated . Patients were classified into 2 groups according to their BMI : non-obese ( < 25 kg/m2 ) and obese ( ≥25 kg/m2 ) . The adipokines evaluated were interleukin-2 , insulin-like growth factor 1 ( IGF-1 ) , chemerin , C-X-C motif chemokine 10 , adiponectin , leptin , and resistin . Multivariate logistic regression analysis was used to identify the independent predictors of advanced tumor stage . Results We found that obese patients with PCa who underwent RP had a higher incidence of tumors with a high Gleason score ( ≥8 ) , pathological T3 ( pT3 ) stage , and positive extraprostatic extension than patients with a normal BMI . Additionally , patients with obesity showed significantly lower serum adiponectin and higher serum leptin levels , but did not show differences in other adipokines . Multivariate analysis demonstrated that IGF-1 ( odds ratio [OR]=1.03 ) was identified as a predictor of advanced tumor stage ( ≥pT3 ) in the overall population . However , only leptin remained an independent predictive factor for advanced tumor stage ( ≥pT3 ) ( OR=1.15 ) in patients with obesity . Conclusions In conclusion , our results indicate that a higher leptin level in obese men can be considered a risk factor for aggressive PCa . This prospect i ve study provides greater insight into the role of circulating adipokines in Korean patients with PCa undergoing RP , particularly in patients with obesity Background Whether and how n-3 and n-6 polyunsaturated fatty acids ( PUFAs ) are related to type 2 diabetes ( T2D ) is debated . Objective ly measured plasma PUFAs can help to clarify these associations . Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries .  Country-specific hazard ratios ( HRs ) were estimated using Prentice-weighted Cox regression and pooled by r and om-effects meta- analysis . We also systematic ally review ed published prospect i ve studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct . In EPIC-InterAct , among long-chain n-3 PUFAs , α-linolenic acid ( ALA ) was inversely associated with T2D ( HR per st and ard deviation [ SD ] 0.93 ; 95 % CI 0.88–0.98 ) , but eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were not significantly associated . Among n-6 PUFAs , linoleic acid ( LA ) ( 0.80 ; 95 % CI 0.77–0.83 ) and eicosadienoic acid ( EDA ) ( 0.89 ; 95 % CI 0.85–0.94 ) were inversely related , and arachidonic acid ( AA ) was not significantly associated , while significant positive associations were observed with γ-linolenic acid ( GLA ) , dihomo-GLA , docosatetraenoic acid ( DTA ) , and docosapentaenoic acid ( n6-DPA ) , with HRs between 1.13 to 1.46 per SD . These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases . Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs . Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA ( ALA ) but no convincing association of marine-derived n3 PUFAs ( EPA and DHA ) with T2D . Moreover , they highlight that the most abundant n6-PUFA ( LA ) is inversely associated with T2D . The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class HighlightsChemerin and leptin are increased , omentin‐1 and visfatin are decreased in at term GDM‐obese women .  Chemerin and omentin‐1 are expressed mainly by the maternal VAT . Leptin is expressed mainly in maternal SAT.Circulating chemerin and leptin in at term pregnancy correlate with BMI and HOMA‐IR.Chemerin and leptin could contribute to insulin resistance and low grade inflammation that characterizes GDM women complicated by obesity . Weight control during pregnancy is necessary to avoid adverse metabolic complications for the mother and the offspring . & NA ; Maternal adipose tissue and the placenta secrete various molecules commonly called adipokines such as chemerin , omentin‐1 , visfatin , adiponectin , and leptin that are important players in the pathogenesis of insulin resistance . Gestational diabetes mellitus ( GDM ) is defined as a state of glucose intolerance characterized by & bgr;‐cell dysfunction and insulin resistance . To examine whether circulating adipokines and their mRNA expression in the adipose tissue and the placenta are altered in GDM pregnancy , we compared 15 GDM women [ obese ( BMI > 30 ) and non‐obese ( BMI < 30 ) ] to 23 NGT ( normal glucose tolerance ) women [ obese and non‐obese ] , at the time of the Cesarean section .  Circulating chemerin and leptin were higher ( p = 0.009 and p = 0.005 , respectively ) and circulating omentin‐1 , visfatin , as well as the adiponectin/leptin ratio were lower ( p = 0.039 , p = 0.007 and p = 0.011 , respectively ) in GDM‐obese compared to NGT‐non‐obese women . Chemerin and leptin correlated positively with BMI and HOMA‐IR and omentin‐1 correlated negatively with BMI . Serum TNF‐&agr ; was significantly elevated in all obese compared to non‐obese pregnant women and correlated positively with BMI . Adiponectin levels were reduced ‐although not significantly‐ in GDM‐ and NGT‐obese women compared to their non‐obese counterparts . Resistin , RPB4 and IL‐6 levels did not differ significantly between groups . Chemerin mRNA expression in subcutaneous adipose tissue ( SAT ) and visceral adipose tissue ( VAT ) was significantly higher compared to placenta in all women ( 6‐to 24‐times , p < 0.05 ) . Chemerin‐VAT mRNA expression in GDM‐obese tended to be significantly higher compared to NGT‐non‐obese women ( 3‐times , p = 0.005 ) . Omentin‐1 mRNA expression was significantly higher in VAT compared to SAT ( 50‐ to 100‐times , p < 0.01 ) and its expression in placenta was negligible in all women . Although , leptin was expressed significantly higher in SAT compared to VAT and the placenta in all women ( 5‐ to 46‐times , p < 0.05 ) , only its mRNA expression in VAT of obese ( GDM and NGT ) differed significantly when compared to NGT‐non‐obese women ( 3‐times higher , p < 0.02 ) . Visfatin mRNA expression was comparable in all tissues . In conclusion , chemerin and leptin are elevated and omentin‐1 and visfatin levels are decreased in GDM women complicated by obesity . This finding together with the positive association of chemerin and leptin with markers of insulin resistance , suggests that these adipokines and more especially chemerin and leptin accompanied by their adipose tissue expression could contribute to the increased insulin resistance and low grade inflammation that characterizes GDM‐obese women 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 Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue . Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome , type 2 diabetes , or both in adults and adolescents . OBJECTIVE The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [ 25(OH)D ] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation . DESIGN Obese adolescent patients [ n = 35 ; mean ± SD age : 14.1 ± 2.8 y ; BMI ( in kg/m(2 ) ) : 39.8 ± 6.1 ; 25(OH)D : 19.6 ± 7.1 ng/mL ] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were r and omly assigned to receive either vitamin D3 ( 4000 IU/d ) or placebo as part of their st and ard care . Anthropometric measurements , inflammatory markers ( IL-6 , TNF-α , C-reactive protein ) , adipokines ( leptin , adiponectin ) , fasting glucose , fasting insulin , and HOMA-IR values were measured at baseline and at 2 follow-up visits ( 3 and 6 mo ) . RESULTS After 6 mo , there were no significant differences in BMI , serum inflammatory markers , or plasma glucose concentrations between groups . Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations ( 19.5 compared with 2.8 ng/mL for placebo ; P < 0.001 ) , fasting insulin ( -6.5 compared with + 1.2 μU/mL for placebo ; P = 0.026 ) , HOMA-IR ( -1.363 compared with + 0.27 for placebo ; P = 0.033 ) , and leptin-to-adiponectin ratio ( -1.41 compared with + 0.10 for placebo ; P = 0.045 ) . Inflammatory markers remained unchanged . CONCLUSION The correction of poor vitamin D status through dietary supplementation may be an effective addition to the st and ard treatment of obesity and its associated insulin resistance . This trial was registered at clinical trials.gov as NCT00994396
Conclusion Plant and marine sources of n-3 PUFAs can modify serum leptin and adiponectin levels by increasing adiponectin and decreasing leptin levels in patients with type 2 diabetes .
Due to some limitations in this study , further studies are needed to reach a definitive conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin in T2DM
Abstract Aim N-3 PUFAs can potentially influence levels of inflammatory and non-inflammatory adipokines .
Given the contradictory effects of n-3 PUFAs on serum levels of adipokines in type 2 diabetes , we conducted a systematic review and meta- analysis study of r and omized placebo-controlled clinical trials that examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in patients with type 2 diabetes .