title: Supplementation with n3 fatty acid ethyl esters increases large and small artery elasticity in obese adults on a weight loss diet. 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. Incidence of diabetes and serum adipokines in Catalonian men. The ADIPOCAT study 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 Biological Effects of Add-On Eicosapentaenoic Acid Supplementation in Diabetes Mellitus and Co-Morbid Depression: A Randomized Controlled Trial The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Eicosapentaenoic acid improves glycemic control in elderly bedridden patients with type 2 diabetes. Effects of n-3 polyunsaturated fatty acids (PUFAs) on circulating adiponectin and leptin in subjects with type 2 diabetes mellitus. Efficacy of omega-3 fatty acid supplementation on serum levels of tumour necrosis factor-alpha, C-reactive protein and interleukin-2 in type 2 diabetes mellitus patients. Serum Omega-3 Polyunsaturated Fatty Acids and Risk of Incident Type 2 Diabetes in Men: The Kuopio Ischemic Heart Disease Risk Factor Study Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects.
abstract: Increased arterial stiffness is associated with enhanced risk of cardiovascular disease in obese individuals . Whether n3 fatty acid ethyl ester ( FAEE ) supplementation improves arterial stiffness in obese participants on a weight loss diet has not yet been investigated . The objective of the study was to carry out a 12-wk r and omized , single-blind trial to test the effect of a 25 % energy deficit weight loss diet alone ( WL ) ( n = 12 ) or WL plus 4 g/d Omacor ( 46 % EPA and 38 % DHA ) supplementation ( WL+FAEE ) ( n = 13 ) on arterial elasticity in obese adults .  Large ( C1 ) and small artery elasticity ( C2 ) were measured by pulse contour analysis of the radial artery . WL alone reduced ( P < 0.05 in all ) body weight ( -3 % ) , waist circumference ( -4 % ) , systolic ( -3 % ) and diastolic ( -3 % ) blood pressures , cardiac output ( -4 % ) , plasma TG concentration ( -25 % ) , and the homeostasis model assessment ( HOMA ) score ( -12 % ) and increased plasma HDL cholesterol ( + 9 % ) and adiponectin ( + 18 % ) concentrations . However , WL alone did not alter C1 and C2 . The WL+FAEE intervention significantly reduced body weight ( -4 % ) , waist circumference ( -4 % ) , systolic ( -8 % ) and diastolic ( -5 % ) blood pressures , pulse pressure ( -5 % ) , heart rate ( -8 % ) , plasma TG concentration ( -36 % ) , and HOMA score ( -12 % ) and increased stroke volume ( + 3 % ) , plasma HDL cholesterol ( + 6 % ) and adiponectin concentrations ( + 28 % ) , and C1 ( + 20 % ) and C2 ( + 22 % ) artery elasticity . The changes in systolic blood pressure , heart rate , plasma TGs , C1 , and C2 were significantly greater in the WL+FAEE group than in the WL group . Supplementation with n3 FAEEs improves C1 and C2 independently of weight loss in obese adults 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 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 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 Background Eicosapentaenoic acid ( EPA ) may reduce increased risks for ( cardiovascular ) morbidity and mortality in patients with diabetes mellitus ( DM ) and comorbid major depressive depression ( MDD ) . Yet , effects of EPA-supplementation on biological risk factors for adverse outcomes have not been studied in DM- patients with MDD . Methods We performed a r and omized , double-blind trial ( n = 25 ) comparing add-on ethyl-EPA-supplementation to placebo on ( I ) oxidative stress , ( II ) inflammatory , ( III ) hypothalamic-pituitary-adrenal (HPA)-axis , ( IV ) one-carbon-cycle , ( V ) fatty acid metabolism and ( VI ) lipoprotein parameters during 12-weeks ' follow-up . Results Besides increases in supplemented α-tocopherol [ estimate ( 95 % CI ) ; 3.62 ( 1.14–6.11 ) µmol/l ; p = 0.006 ] and plasma and erythrocyte EPA , the intervention did not influence other oxidative stress , inflammatory or one-carbon-cycle parameters compared to placebo . HPA-axis reactivity significantly decreased in the EPA-group ( N = 12 ) [ AUCi : −121.93 ( −240.20–−3.47 ) min × nmol/l ; p = 0.045 ] , not in the placebo-group ( N = 12 ) . Furthermore , EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid , and decreased plasma arachidonic acid ( AA ) concentrations [ −1.61 ( −3.10–−0.11 ) % ; p = 0.036 ] . Finally , EPA had a multivariate influence on lipoprotein concentrations ( p = 0.030 ) , reflected by relative increases in high density lipoprotein [ HDL ; 0.30 ( 0.02–0.58 ) mmol/l ; p = 0.039 ] and total cholesterol concentrations [ 1.01 ( 0.29–1.72 ) mmol/l ; p = 0.008 ] . Conclusion Overall , add-on EPA-supplementation had limited effects on biological risk factors for adverse outcome in this sample of DM- patients with comorbid MDD . Besides increases in concentrations of supplemented α-tocopherol and EPA , AA decreased , and inconclusive effects on HPA-axis (re)activity and lipoprotein concentrations were observed . Therefore , further studies on the alleged beneficial effects of EPA-supplementation on biological risk factors for adverse outcome in DM- patients with comorbid MDD seem warranted , preferably using clinical outcomes such as ( cardiovascular ) DM-complications . Trial Registration Controlled-Trials.com IS RCT N30877831 IS RCT Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) are ω3-polyunsaturated fatty acids mainly contained in the blue-backed fish oil , and are effective in decreasing the lipids disorder and the cardiovascular incidence among diabetic patients . Moreover , it has been suggested that EPA and DHA may improve the insulin resistance and glucose metabolism . However , the clinical effects of EPA and DHA on glucose metabolism remain unclear . We aim ed to clarify the effects of EPA/DHA treatment on glycemic control in type 2 diabetes mellitus . This study was a multicenter prospect i ve r and omized controlled trial involving 30 elderly type 2 diabetic patients on a liquid diet .  Their exercises were almost zero and the content of their meals was strictly managed and understood well . Therefore , the difference by the individual 's life was a minimum . The subjects were divided into two groups : those receiving EPA/DHA-rich liquid diet [ EPA/DHA ( + ) ] or liquid diet lacking EPA/DHA [ EPA/DHA ( - ) ] . Changes in factors related to glucose and lipid metabolism were assessed after the three-month study . Serum concentrations of EPA rose in EPA/DHA ( + ) , although the levels of DHA and fasting C-peptide remained unchanged in EPA/DHA ( + ) . In addition , there was a significant decline in the fasting plasma glucose ( FPG ) , hemoglobin A1c ( HbA1c ) , fasting remnant-like particles and apolipoprotein ( apo ) B in EPA/DHA ( + ) , compared with the values in EPA/DHA ( - ) . EPA/DHA-rich diet might improve glucose metabolism in elderly type 2 diabetic patients on a liquid diet . This phenomenon may be due to the improved insulin resistance mediated by the rise in serum EPA concentrations 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 INTRODUCTION Consumption of omega-3 fatty acids can alter the inflammatory response in diabetic patients . This study aim ed to determine the effects of omega-3 fatty acid supplementation on the serum levels of C-reactive protein ( CRP ) , interleukin (IL)-2 and tumour necrosis factor-alpha ( TNF-α ) in type 2 diabetes mellitus patients . METHODS A r and omised , double-blind , placebo-controlled clinical trial was conducted on 84 subjects aged 45 - 85 years with at least a two-year history of type 2 diabetes mellitus . Participants were r and omly assigned to the treatment or control group . Each subject in the treatment group received three omega-3 capsules per day ( eicosapentaenoic acid 1,548 mg ; docosahexaenoic acid 828 mg ; other omega-3 fatty acids 338 mg ) , while each subject in the control group received three placebo capsules ( sunflower oil 2,100 mg ) for a period of eight weeks . At the beginning of the study and post intervention , fasting blood sample s were taken and serum concentrations of IL-2 , TNF-α and CRP were assessed and compared . RESULTS Serum IL-2 and TNF-α levels were significantly reduced in the treatment group compared to the controls ( p < 0.01 ) . There was no significant change in serum CRP levels . CONCLUSION Short-term omega-3 fatty acid supplementation ( 3 g/day for eight weeks ) can decrease the serum levels of TNF-α and IL-2 in diabetic patients , with no change in CRP levels . Consumption of omega-3 fatty acid supplements is highly recommended to alleviate inflammation caused by type 2 diabetes mellitus OBJECTIVE The relationship between fish or omega-3 polyunsaturated fatty acids ( PUFAs ) and type 2 diabetes is inconclusive . Even contaminants in fish , such as mercury , may modify the effects . We investigated the associations between serum omega-3 PUFAs eicosapentaenoic acid ( EPA ) , docosapentaenoic acid ( DPA ) , docosahexaenoic acid ( DHA ) , α-linolenic acid ( ALA ) , hair mercury , and risk of incident type 2 diabetes in middle-aged and older Finnish men . RESEARCH DESIGN AND METHODS A total of 2,212 men from the prospect i ve , population -based Kuopio Ischemic Heart Disease Risk Factor study , aged 42–60 years and free of type 2 diabetes at baseline in 1984–1989 , were investigated . Serum PUFA and hair mercury were used as biomarkers for exposure . Dietary intakes  were assessed with 4-day food recording . Type 2 diabetes was assessed by self-administered question naires and fasting and 2-h oral glucose tolerance test blood glucose measurement at re-examination rounds 4 , 11 , and 20 years after the baseline and by record linkage to hospital discharge registry and reimbursement register on diabetes medication expenses . Cox proportional hazards models were used to analyze associations . RESULTS During the average follow-up of 19.3 years , 422 men developed type 2 diabetes . Men in the highest versus the lowest serum EPA + DPA + DHA quartile had 33 % lower multivariate-adjusted risk for type 2 diabetes ( 95 % CI 13–49 ; P trend 0.01 ) . No statistically significant associations were observed with serum or dietary ALA , dietary fish or EPA + DHA , or hair mercury . CONCLUSIONS Serum long-chain omega-3 PUFA concentration , an objective biomarker for fish intake , was associated with long-term lower risk of type 2 diabetes Background : Obesity , inflammation , insulin resistance and cardiovascular disease ( CVD ) risk are inter-related . Both weight-loss and long-chain n-3 polyunsaturated fatty acids ( LC n-3 PUFA ) are independently known to reduce metabolic risk , but the combined effects are unclear . Objective : This study examines whether addition of LC n-3 PUFA to a low fat/high carbohydrate weight-loss programme results in greater improvements in inflammation , insulin sensitivity and CVD risk , than weight-loss alone . Design : One hundred and sixteen overweight insulin-resistant women entered a 24-week r and omised intervention study . Thirty-nine women were r and omised to a weight-loss programme , with LC n-3 PUFA ( WLFO ) , 38 to a weight-loss programme with placebo oil ( WLPO ) , and 39 to receive placebo oil , with no weight-loss programme ( control ) . Results : Ninety-three women completed the study ( 35 WLFO , 32 WLPO and 26 control ) , with significant weight-loss in WLFO ( 10.8±1.0 % ) and WLPO ( 12.4±1.0 % ) compared to the control group ( P<0.0001 ) . The WLFO , but not WLPO or control group , showed significant increases in adipose tissue LC n-3 PUFA ( 0.34±0.20 vs 0.17±0.10 and 0.16±0.10 % DHA , P<0.0001 ) . Weight-loss showed significant improvements in insulin sensitivity ( P<0.001 ) , lipid profile ( triglycerides P<0.05 ) and inflammation ( sialic acid P<0.05 ) . Time*group effects showed significant decreases in triglycerides ( P<0.05 ) and increases in adiponectin ( P<0.01 ) with LC n-3 PUFA , in the WLFO vs WLPO groups . Conclusions : Weight-loss improved risk factors associated with CVD , with some additional benefits of LC n-3 PUFA on triglycerides and adiponectin . Given the current low dietary intake of LC n-3 PUFA , greater attention should be given to increase these fatty acids in the treatment of obesity n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention .  Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects
target: Levels of other adipocytokines were not significantly affected .
  CONCLUSION Eicosapentaenoic acid and docosahexaenoic acid supplementation may increase adiponectin and reduce TNF-α levels in this population group .
background: BACKGROUND The objective of this systematic review and meta- analysis was to determine the effects of omega-3 supplementation on adipocytokine levels in adult prediabetic and diabetic individuals .