title: The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients. Fish Oil–Induced Changes in Apolipoproteins in IDDM Subjects 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. (n-3) fatty acid supplementation in moderately hypertriglyceridemic adults changes postprandial lipid and apolipoprotein B responses to a standardized test meal. Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes. Randomized Controlled Trial Investigating the Effects of a Low–Glycemic Index Diet on Pregnancy Outcomes in Women at High Risk of Gestational Diabetes Mellitus: The GI Baby 3 Study Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study A randomized controlled clinical trial investigating the effect of DASH diet on insulin resistance, inflammation, and oxidative stress in gestational diabetes. Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report 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. Effects of fish oil on VLDL triglyceride kinetics in humans. N-3 fatty acid supplementation to routine statin treatment inhibits platelet function, decreases patients’ daytime blood pressure, and improves inflammatory status Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Can metformin reduce the incidence of gestational diabetes mellitus in pregnant women with polycystic ovary syndrome? Prospective cohort study Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients: a double-blind placebo-controlled study. The effect of fatty or lean fish intake on inflammatory gene expression in peripheral blood mononuclear cells of patients with coronary heart disease Serum Antibody Levels to Actinobacillus actinomycetemcomitans Predict the Risk for Coronary Heart Disease Effect of omega-3 fatty acids on cardiovascular risk factors in patients with type 2 diabetes mellitus and hypertriglyceridemia: an open study. Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. Effects of omega-3 polyunsaturated fatty acids on plasma indices of thrombogenesis and inflammation in patients post-myocardial infarction. Efficacy of collagen matrix seal and collagen sponge on ridge preservation in combination with bone allograft: A randomized controlled clinical trial Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Effects of Fish Oil Supplements in NIDDM Subjects: Controlled Study A Comparison between Primary and Secondary Flap Coverage in Ridge Preservation Procedures: A Pilot Randomized Controlled Clinical Trial
abstract: BACKGROUND AND AIMS Cardiovascular diseases are the major cause of mortality among diabetic patients . The concentration of malondialdehyde ( MDA ) and homocysteine is believed to play a role in cardiovascular diseases . Omega-3 fatty acid supplementation could be effective in some diabetes complications and in the control of the glycemic index . However , it may increase lipid peroxidation . The objective of this study was to determine the effect of omega-3 fatty acids on the concentration of homocysteine and MDA in diabetic patients . METHODS AND RESULTS A r and omized double-blind , placebo-controlled clinical trial was conducted on 81 patients with type 2 diabetes . The patients were r and omly assigned to either the treatment or control groups . Each subject received three capsules of omega-3 fatty acids or a placebo every day for a period of 2months . The two groups were similar in terms of body mass index and food intake . At the beginning of the study and after 2months of supplementation their levels of HbA(1)c , homocysteine , MDA , C-reactive protein ( CRP ) , total cholesterol , LDL-cholesterol and fasting blood sugar ( FBS ) were determined . Due to omega-3 fatty acid supplementation , homocysteine was changed significantly in both treatment and control groups up to -3.10mumol/L and 0.10mumol/L respectively , and HbA(1)c decreased by 0.75 % in the treatment group and increased by 0.26 % in the control group . However , the changes in fasting blood sugar ( FBS ) , malondialdehyde ( MDA ) , C-reactive protein ( CRP ) , total cholesterol and LDL-cholesterol levels were not significant . CONCLUSION The consumption of omega-3 fatty acid supplements ( 3g/day ) for 2months decreases the levels of homocysteine in diabetic patients with no change in FBS , MDA and CRP levels The aim of this study was to examine the effect of Max EPA ( a commercially available fish oil preparation ) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic ( IDDM ) men with dosages that were likely to be acceptable to patients . Twenty-two male IDDM patients aged 20–41 yr , 6 of whom had retinopathy , were recruited from the Royal Perth Hospital diabetic clinic . After screening , subjects were divided into three groups . Six of the subjects without retinopathy were r and omly selected and allocated to a control group . The remaining 16 patients ( 10 without and 6 with retinopathy ) received a fish oil supplement . All subjects were advised to maintain their usual dietary patterns . Sixteen patients , including the 6 with retinopathy , were instructed to take 15 Max EPA fish oil capsules/day with meals . Patients in the control group did not take Max EPA . Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol ( P < 0.01 ) , which could be accounted for by increases in low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol . The increase in HDL cholesterol was explained by a 33 % rise ( P < 0.001 ) in its HDL2 subclass . Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-l increased after ingestion of fish oil and correlated significantly ( P < 0.05 ) with the rise in HDL cholesterol . Apolipoprotein A-ll showed a significant fall at the end of Max EPA intake in a subgroup of patients with retinopathy , and this correlated significantly ( P < 0.05 ) with the fall in HDL3 cholesterol observed at this time . A significant rise in apolipoprotein B ( P < 0.05 ) was correlated with the rise in LDL cholesterol . Possible adverse effects of the increase in both total and LDL cholesterol after 15 g/day Max EPA may be compensated for by a rise in the protective HDL2 subclass . However , in view of this hypercholesterolemic effect and evidence that suggests that LDL apolipoprotein B may be a risk factor for coronary heart disease , these findings raise questions regarding the safety of fish oils in patients with IDDM 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 The effects of ( n-3 ) fatty acids on the postpr and ial state were investigated by monitoring the alimentary responses to identical test meals fed to adults [ n = 11 ; fasting triacylglycerol ( TG ) 2.55 + /- 0.24 mmol/L ; mean + /- SEM ] after a self-selected diet baseline period ( BLP ) and then after a 6-wk ( n-3 ) fatty acid period ( FOP ) [ approximately 5.2 g ( n-3 ) fatty acids ] and a 6-wk control oil period ( COP ) administered in r and om order . Sample s were drawn immediately prior to the test meal ( time 0 ) and then hourly from 2 to 6 h postmeal . Postpr and ial plasma triacylglycerol ( TG ) and TG-rich lipoprotein ( TRL ) TG apo B48 , and B100 absolute concentrations were significantly lower after FOP than after COP or BLP , while plasma cholesterol was unchanged . Normalizing the results as increments over time 0 eliminated the diet effect on all but plasma TG . Time remained a significant effect for plasma TG , TRL TG , and TRL TC . Finally , only absolute TRL B48 and absolute and incremental plasma TG concentrations displayed significant time-diet interactions . These results suggest that postpr and ial TRL apo B reductions are likely caused by ( n-3 ) fatty acid suppression of both hepatic and intestinal apoB secretion/ synthesis . Altered TRL metabolism , i.e. changes in postpr and ial TG , cholesterol , apo B48 , and increase in LDL particle size , may represent an additional mechanism for the reduced heart disease risk associated with fish [ ( n-3 ) fatty acid ] consumption BACKGROUND Plasma lipoproteins may be classified by their apolipoprotein composition . The lipoprotein subclass containing apolipoproteins B and C ( LpB : C ) is considered the most atherogenic . OBJECTIVE We evaluated the acute effects of individual fatty acids on apolipoprotein B ( apo B)-containing lipoproteins in adults with type 2 diabetes ( n = 15 ) . DESIGN We administered 3 meals in a r and omized , double-blind , crossover design . Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils ( monounsaturated fatty acid ; MUFA ) , MUFA + 3.5 g alpha-linolenic acid ( ALA ; MUFA + ALA ) from high-ALA canola oil , or MUFA + 4.0 g both eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ; MUFA + EPA/DHA ) from sardine oil .  Apo B , LpB , LpB : C , LpB : E + LpB : C : E , and LpA-II : B : C : D : E were measured at baseline and 2 and 4 h after the meal . Flow-mediated dilation was measured at baseline and 4 h after the meal . RESULTS The treatments significantly increased apo B and LpB postpr and ially ( P < 0.03 for both ) , but the magnitude of the changes did not differ significantly between the treatments . The postpr and ial change in LpB : C was 23 % lower after MUFA + EPA/DHA than after MUFA ( treatment x time interaction , P < 0.0001 ) . MUFA + ALA attenuated the increase in LpA-II : B : C : D : E in those with high triacylglycerols ( > /=1.69 mmol/L ) but was the only treatment to significantly increase this particle in those with low triacylglycerols ( treatment x group interaction , P < 0.0001 ) . Examination of change scores did not reveal the source of the interaction of treatment and time ( P < 0.007 ) for LpB : E + LpB : C : E. Furthermore , the subjects with the largest increases in LpB : C exhibited the largest impairment in endothelial function . CONCLUSIONS The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses . A rise in LpB : C adversely affects endothelial function . Meals containing MUFA + EPA/DHA attenuated the postpr and ial rise in LpB : C and the impairment of endothelial function OBJECTIVE Dietary interventions can improve pregnancy outcomes in women with gestational diabetes mellitus ( GDM ) . We compared the effect of a low – glycemic index ( GI ) versus a conventional high-fiber ( HF ) diet on pregnancy outcomes , birth weight z score , and maternal metabolic profile in women at high risk of GDM . RESEARCH DESIGN AND METHODS One hundred thirty-nine women [ mean ( SD ) age 34.7 ( 0.4 ) years and prepregnancy BMI 25.2 ( 0.5 ) kg/m2 ] were r and omly assigned to a low-GI ( LGI ) diet ( n = 72 ; target GI ∼50 ) or a high-fiber , moderate-GI ( HF ) diet ( n = 67 ; target GI ∼60 ) at 14–20 weeks ’ gestation .  Diet was assessed by 3-day food records and infant body composition by air-displacement plethysmography , and pregnancy outcomes were assessed from medical records . RESULTS The LGI group achieved a lower GI than the HF group [ mean ( SD ) 50 ( 5 ) vs. 58 ( 5 ) ; P < 0.001 ] . There were no differences in glycosylated hemoglobin , fructosamine , or lipids at 36 weeks or differences in birth weight [ LGI 3.4 ( 0.4 ) kg vs. HF 3.4 ( 0.5 ) kg ; P = 0.514 ] , birth weight z score [ LGI 0.31 ( 0.90 ) vs. HF 0.24 ( 1.07 ) ; P = 0.697 ] , ponderal index [ LGI 2.71 ( 0.22 ) vs. HF 2.69 ( 0.23 ) kg/m3 ; P = 0.672 ] , birth weight centile [ LGI 46.2 ( 25.4 ) vs. HF 41.8 ( 25.6 ) ; P = 0.330 ] , % fat mass [ LGI 10 ( 4 ) vs. HF 10 ( 4 ) ; P = 0.789 ] , or incidence of GDM . CONCLUSIONS In intensively monitored women at risk for GDM , a low-GI diet and a healthy diet produce similar pregnancy outcomes Background Omega–3 fatty acids prevent cardiovascular disease ( CVD ) events in patients with myocardial infa rct ion or heart failure . Benefits in patients without overt CVD have not been demonstrated , though most studies did not use treatment doses ( 3.36 g ) of omega-3 fatty acids .  Arterial stiffness measured by pulse wave velocity ( PWV ) predicts CVD events independent of st and ard risk factors . However , no therapy has been shown to reduce PWV in a blood pressure-independent manner . We assessed the effects of esterified omega–3 fatty acids on PWV and serum markers of inflammation among patients with hypertension . Design and methods We performed a prospect i ve , r and omized ; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban , safety net hospital . Patients received 3.36 g of omega–3 fatty acids vs. matched placebo daily for 3-months . The principal outcome measure was change in brachial-ankle PWV . Serum inflammatory markers associated with CVD risk were also assessed . Results The majority ( 71 % ) were of Latino ethnicity . After 3-months , mean change in arterial PWV among omega-3 and placebo groups was −97 cm/s vs. −33 cm/s respectively ( p = 0.36 for difference , after multivariate adjustment for baseline age , systolic blood pressure , and serum adiponectin ) . Non-significant reductions in lipoprotein-associated phospholipase A2 ( LpPLA2 ) mass and high sensitivity C-reactive protein ( hsCRP ) relative to placebo were also observed ( p = 0.08 , and 0.21 , respectively ) . Conclusion High-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension . Clinical trial registration NCT00935766 , registered July 8 2009 OBJECTIVE To our knowledge , no reports are available indicating the effects of the dietary approaches to stop hypertension ( DASH ) eating plan on insulin resistance , inflammation , and oxidative stress among pregnant women with gestational diabetes mellitus ( GDM ) . This study was design ed to investigate the effects of the DASH diet on insulin resistance , serum high-sensitivity C-reactive protein ( hs-CRP ) and biomarkers of oxidative stress among pregnant women with GDM . METHODS This r and omized controlled clinical trial was performed with 32 pregnant women diagnosed with GDM at 24 to 28 wk gestation . Participants were r and omly assigned to consume either the control ( n = 16 ) or DASH diet ( n = 16 ) for 4 wk . The DASH diet was rich in fruits , vegetables , whole grains , and low-fat dairy products and was low in saturated fats , total fats , cholesterol , refined grains , and sweets , with a total of 2400 mg/d of sodium . The control diet contained 40 % to 55 % of its energy as carbohydrates , 10 % to 20 % as proteins , and 25 % to 30 % as total fats . Fasting blood sample s were taken at baseline and after 4 wk of intervention to measure fasting plasma glucose ( FPG ) , serum insulin , and hs-CRP , homeostasis model of assessment -insulin resistance ( HOMA-IR ) , plasma total antioxidant capacity ( TAC ) , and total glutathione levels ( GSH ) . RESULTS Consumption of the DASH diet compared with the control diet result ed in decreased FPG ( -7.62 versus 3.68 mg/dL ; P = 0.02 ) , serum insulin levels ( -2.62 versus 4.32 μIU/mL , P = 0.03 ) , and HOMA-IR score ( -0.8 versus 1.1 ; P = 0.03 ) . Increased concentrations of plasma TAC ( 45.2 versus -159.2 mmol/L ; P < 0.0001 ) and GSH ( 108.1 versus -150.9 μmol/L ; P < 0.0001 ) also were seen in the DASH group compared with control group . We failed to find a significant difference in mean changes of serum hs-CRP levels between the two diets . Within-group comparisons revealed significant reductions in plasma TAC and GSH levels in the control diet , while a significant increase in these biomarkers in the DASH diet . CONCLUSION Consumption of the DASH diet in pregnant women with GDM had beneficial effects on FPG , serum insulin levels , HOMA-IR score , plasma TAC , and total GSH levels . The effects of this dietary pattern on pregnancy outcomes need to be investigated in future studies BackgorundMixed hyperlipidemia is common in patients with diabetes .  Statins , the choice drugs , are effective at reducing lipoproteins that contain apolipoprotein B100 , but they fail to exert good control over intestinal lipoproteins , which have an atherogenic potential . We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day . Methods Patients with type 2 diabetes and mixed hyperlipidemia were recruited .  Fasting lipid profile was taken when patients were treated with diet , diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids . The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA . Results The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides , VLDL triglycerides and the triglyceride/HDL cholesterol ratio , and an increase in HDL cholesterol ( P < 0.05 ) . Fluvastatin induced a reduction of 26 % in B100 ( P < 0.05 ) and 14 % in B48 ( NS ) . However , the addition of omega 3 fatty acids enhanced this reduction to 32 % in B100 ( NS ) and up to 36 % in B48 ( P < 0.05 ) . Conclusion Our preliminary findings therefore suggest an additional benefit on postpr and ial atherogenic particles when omega 3 fatty acids are added to st and ard treatment with fluvastatin 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 Dietary n-3 fatty acids ( FAs ) found in fish oils markedly lower plasma triglyceride ( TG ) and very low density lipoprotein ( VLDL ) levels in both normal and hypertriglyceridemic subjects . The present study examined the mechanism of this effect . Ten subjects with widely different plasma triglyceride levels ( 82 to 1002 mg/dl ) were fed metabolically controlled diets containing 20 % fat . The control diet contained a blend of cocoa butter and peanut oil ( P/S = 0.8 ) . The test diet contained fish oil ( P/S = 1.1 ) and provided 10 - 17 g of n-3 FAs per day ( depending on calorie intake ) . After 3 to 5 weeks of each diet , the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol . The fish oil diet reduced the VLDL-TG synthetic rate from 23 + /- 14.3 ( mean + /- SD ) to 12.6 + /- 7.5 mg/h per kg ideal weight ( P less than 0.005 ) and increased the fractional catabolic rate ( FCR ) for VLDL-TG from 0.23 + /- 0.12 to 0.38 + /- 0.16 h -1 ( P less than 0.005 ) . At the same time , there was a 66 % reduction of plasma triglyceride levels , result ing largely from a 78 % decrease in VLDL-TG levels ( 398 + /- 317 to 87 + /- 77 mg/dl ; P less than 0.005 ) . There was a strong correlation ( r = 0.83 ; P less than 0.01 ) between the change in synthetic rates and pool sizes , but there was no correlation ( r = 0.24 ; NS ) between changes in FCRs and pool sizes . The VLDL cholesterol : triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present . These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR . We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis , but an additional , independent effect upon VLDL catabolism can not be ruled out Objectives N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality . Administration of N-3 fatty acids to patients treated with statins  may potentiate the treatment effects . We examined the operating mechanisms underlying such a combination . Methods Thirty-two hypercholesterolemic patients aged 30–70 years with hypercholesterolemia controlled by statins  , received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks . Scheduled clinical visits included physical examination , 24-h blood pressure measurement , endothelial function evaluated by pulse wave analysis , analyses for platelet function , inflammation markers [ interleukin (IL)-6 , plasminogen activator inhibitor-1 ( PAI-1 ) ] and oxidative stress parameters ( STAT-8-Isoprostane ) were undertaken at baseline , after placebo treatment , and after 6 and 20 weeks of N-3 fatty acid intake . Results Platelets functions were significantly inhibited , whereas endothelial function parameters were unaltered . IL-6 significantly decreased whereas PAI-1 and STAT-8-Isoprostane levels remained unaffected . Daytime blood pressure significantly decreased ; however , nighttime pressure and heart rate remained unchanged . No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids . Conclusions In hypercholesterolemic patients , combination of statins and N-3 fatty acid inhibits platelet aggregation , alters inflammatory status , and positively affects daytime blood pressure . Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population BACKGROUND Patients with elevated serum triglyceride ( TG ) levels often have elevations in non-high-density lipoprotein cholesterol ( non-HDL-C ) levels as well . The National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) has identified non-HDL-C as a secondary therapeutic target in these patients , but treatment goals may not be reached with statin monotherapy alone . OBJECTIVE This study evaluated the effects on non-HDL-C and other variables of adding prescription omega-3-acid ethyl esters ( P-OM3 ; Lovaza , formerly Omacor [ Reliant Pharmaceuticals , Inc. , Liberty Corner , New Jersey ] ) to stable statin therapy in patients with persistent hypertriglyceridemia . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled , parallel-group study in adults who had received > or = 8 weeks of stable statin therapy and had mean fasting TG levels > or = 200 and < 500 mg/dL and mean low-density lipoprotein cholesterol levels < or = 10 % above their NCEP ATP III goal . The study regimen consisted of an initial 8 weeks of open-label simvastatin 40 mg/d and dietary counseling , followed by 8 weeks of r and omized treatment with double-blind P-OM3 4 g/d plus simvastatin 40 mg/d or placebo plus simvastatin 40 mg/d . The main outcome measure was the percent change in non-HDL-C from baseline to the end of treatment . RESULTS The evaluable population included 254 patients , of whom 57.5 % ( 146 ) were male and 95.7 % ( 243 ) were white . The mean ( SD ) age of the population was 59.8 ( 10.4 ) years , and the mean weight was 92.0 ( 19.6 ) kg . At the end of treatment , the median percent change in non-HDL-C was significantly greater with P-OM3 plus simvastatin compared with placebo plus simvastatin ( -9.0 % vs -2.2 % , respectively ; P < 0.001 ) . P-OM3 plus simvastatin was associated with significant reductions in TG ( 29.5 % vs 6.3 % ) and very-low-density lipoprotein cholesterol ( 27.5 % vs 7.2 % ) , a significant increase in high-density lipoprotein cholesterol ( HDL-C ) ( 3.4 % vs -1.2 % ) , and a significant reduction in the total cholesterol : HDL-C ratio ( 9.6 % vs 0.7 % ) ( all , P < 0.001 vs placebo ) . Adverse events ( AEs ) reported by > or= 1 % of patients in the P-OM3 group that occurred with a higher frequency than in the group that received simvastatin alone were nasopharyngitis ( 4 [ 3.3 % ] ) , upper respiratory tract infection ( 4 [ 3.3 % ] ) , diarrhea ( 3 [ 2.5 % ] ) , and dyspepsia ( 3 [ 2.5 % ] ) . There was no significant difference in the frequency of AEs between groups . No serious AEs were considered treatment related . CONCLUSION In these adult , mainly white patients with persistent hypertriglyceridemia , P-OM3 plus simvastatin and dietary counseling improved non-HDL-C and other lipid and lipoprotein parameters to a greater extent than simvastatin alone Background . Women with polycystic ovary syndrome ( PCOS ) are at a high risk to develop Gestational Diabetes mellitus ( GDM ) . We hypothesized that metformin due to its metabolic , endocrine , vascular , and anti-inflammatory effects may reduce the incidence of GDM in PCOS women . Patient and method . We carried out a prospect i ve cohort study to determine the beneficial effects of metformin on PCOS patients during pregnancy . Three-hundred and sixty non-diabetic PCOS patients were included who were conceived on metformin by different treatment modalities . Two-hundred pregnant women continued on metformin at a dose of 1000–2000 mg daily throughout pregnancy ( study group ) and 160 women discontinued metformin use at the time of conception ( control group ) . Results . There is a statistically significant reduction in the incidence of GDM in favor of metformin group ( OR : 0.17 , 95 % CI : 0.07–0.37 ) . There is a statistically significant reduction in the incidence of pre-eclampsia in favor of metformin group ( OR : 0.35 , 95 % CI : 0.13–0.94 ) . Conclusion . Metformin is a promising medication for the prevention or reduction of the incidence of GDM and pre-eclampsia in PCOS women BACKGROUND Marine fish oils improve vascular function , but the mechanism of benefit is unclear . We conducted a study to examine the effects of fish oils given to hypercholesterolemic patients on small artery function in vitro . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled trial , subcutaneous gluteal fat biopsies were taken from 16 hypercholesterolemic patients ( serum total cholesterol , 7.97+/-0.16 mmol/L [ mean+/-SEM ] ) and 12 age- and sex-matched control subjects ( mean cholesterol , 5.11+/-0.34 mmol/L ) . Small arteries were mounted on a wire myograph for isometric tension experiments . Patients and control subjects were r and omized to receive fish oil ( Maxepa 5 capsules BID ) or placebo for 3 months . A second biopsy was taken and the studies were repeated . Relaxation to acetylcholine was significantly improved in the hypercholesterolemic group given Maxepa but not in the placebo group ( mean maximum relaxation before and after , 48+/-6.2 % and 68.83+/-2.19 % , P=.0054 ) . The dysfunction was not restored to control values ( 84.3+/-5.2 % , P=.0002 ) . There was also a smaller but significant impairment in endothelium-independent relaxation provoked by sodium nitroprusside ( P<.01 ) . A good correlation between the increase in eicosapentanoic acid ( n=3 ) in red cell membrane and improvement in relaxation in the hypercholesterolemic group given fish oils was seen ( r=.781 , P<.02 ) . CONCLUSIONS Marine fish oil significantly improved endothelial function in peripheral small arteries in hypercholesterolemia patients . This may provide a mechanism for the beneficial effects of these fatty acids in coronary heart disease Background Little is known about the effect of fish consumption on gene expression of inflammation-related genes in immune cells in coronary heart disease ( CHD ) . Aim of the study We sought to evaluate the effect of a fatty fish ( FF ) or a lean fish ( LF ) diet on the modulation of inflammatory and endothelial function-related genes in peripheral blood mononuclear cells ( P BMC s ) of subjects with CHD , and its association with serum fatty acid ( FA ) profile and lipid metabolic compounds . Methods Data from 27 patients r and omized into an 8-week FF ( n = 10 ; mean ± SD : 4.3 ± 0.4 portions of fish per week ) , LF ( n = 11 ; 4.7 ± 1.1 portions of fish per week ) , or control diet ( n = 6 ; 0.6 ± 0.4 portions of fish per week ) were analyzed . The mRNA expression was measured using real-time PCR . Results The effect of the intervention on the mRNA expression of the genes studied did not differ among groups . In the FF group , however , the decrease in arachidonic acid to eicosapentaenoic acid ( AA : EPA ) ratio in cholesterol ester and phospholipid fractions strongly correlated with the change in IL1B mRNA levels ( rs = 0.60 , P = 0.06 and rs = 0.86 , P = 0.002 , respectively ) . In the LF group , the decrease in palmitic acid and total saturated FAs in cholesterol esters correlated with the change in intercellular cell adhesion molecule-1 ( ICAM1 ) expression ( rs = 0.64 , P = 0.04 for both ) . Circulating levels of soluble ICAM-1 decreased only in the LF group ( P < 0.05 ) . Conclusions The intake of FF or LF diet did not alter the expression of inflammatory and endothelial function-related genes in P BMC s of patients with CHD . However , the decrease in AA : EPA ratio in serum lipids in the FF group may induce an anti-inflammatory response at mRNA levels in P BMC s. A LF diet might benefit endothelial function , possibly mediated by the changes in serum FA composition Objective —The association between serum antibody levels to major periodontal pathogens and coronary heart disease ( CHD ) was analyzed in a prospect i ve population -based study . Methods and Results —The population comprised 1023 men ( aged 46 to 64 years ) in the Kuopio Ischemic Heart Disease Study . The subjects with CHD at baseline ( n=113 ) were more often seropositive for Porphyromonas gingivalis IgA ( 38.9 % versus 28.5 % , P=0.021 ) and IgG ( 60.2 % versus 46.7 % , P=0.007 ) than those without CHD . During the 10-year follow-up , 109 men free from CHD at baseline experienced an acute myocardial infa rct ion or CHD death . The men with an end point were more often seropositive for Actinobacillus actinomycetemcomitans IgA ( 15.5 % versus 10.2 % , P=0.019 ) than those who remained healthy . In the highest tertile of A. actinomycetemcomitans IgA-antibodies compared with the lowest one , the relative risk ( RR ) for an end point adjusted for CHD risk factors was 2.0 ( 95 % confidence interval [ CI ] , 1.2 to 3.3 ) . In the Porphyromonas gingivalis IgA-antibody tertiles , the highest RR of 2.1 ( 1.3 to 3.4 ) was observed in the second tertile . All antibody levels correlated positively with the carotid artery intima-media thickness . Conclusions —High-serum antibody levels to major periodontal pathogens are associated with sub clinical , prevalent , and future incidence of CHD . Periodontal pathogens or host response against them may contribute to the pathogenesis of CHD BACKGROUND AND OBJECTIVES Epidemiological and interventional studies suggest that a high dietary intake of n-3 polyunsaturated fatty acids may confer a protective effect against atherosclerotic disease and reduce serum triglycerides levels . The aim of our study was to investigate the effectivity on triglyceride levels and inflammatory markers of a concentrated of n-3 fatty acids in patients with type 2 diabetes mellitus and hypertriglyceridaemia . SUBJECTS A total of 30 patients ( 16 males and 14 females ) with diabetes mellitus type 2 and hypertriglyceridemia ( > 200 mg/dl ) were included in the study . Patients received two capsules of eicosapentaenoic 465 mg and docosahexanoic 375 mg daily for 12 weeks . RESULTS Triglycerides levels and non HDL-cholesterol decreased ( 326 + /- 113.5 vs. 216.4 + /- 57 mg/dl ; p < 0.05 ) and ( 103.87 + /- 44 vs. 89.6 + /- 14 mg/dl ; p < 0.05 ) , respectively . HDL-cholesterol levels increased ( 39.6 + /- 10.7 vs. 46.4 + /- 8.7 mg/dl ; p < 0.05 ) . C reactive protein decreased ( 5.98 + /- 3.9 vs. 3.9 + /- 1.6 mg/dl ; p < 0.05 ) and TNF-alpha levels decreased ( 16.24 + /- 5.5 vs. 13.3 + /- 5.8 pg/dl ; p < 0.05 ) , without significant changes in IL-6 levels . In conclusion , an n-3 polyunsaturated intervention improved lipid profile and inflammatory markers in patients with diabetes mellitus type 2 and hypertriglyceridaemia Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients . Lipid abnormalities are found frequently in these patients , and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease . However , the optimal lipid-lowering therapy after cardiac transplantation has not been defined . In an open , r and omized study , the efficacy and safety of bezafibrate ( 400 mg/day ) and fish oil ( Maxepa ) ( 10 g/day ) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter , or both . After 1 month , bezafibrate reduced total cholesterol by 13 % , low-density lipoprotein cholesterol by 20 % and apolipoprotein B by 13 % . It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20 % , respectively , and significantly reduced fibrinogen at 3 months . Maxepa had no significant effect on these variables , but was as effective as bezafibrate in reducing triglycerides ( 36 and 31 % , respectively ) . Both drugs increased lipoprotein ( a ) to a similar extent , and bezafibrate significantly increased serum creatinine . These results suggest that bezafibrate has better lipid- , apolipoprotein- and hemostatic modifying properties than does Maxepa , but its potentially adverse effect on renal function needs further investigation BACKGROUND N-3 polyunsaturated fatty acids ( PUFAs ) from oily fish protect against death from cardiovascular disease . We aim ed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability , respectively . METHODS We did a r and omised controlled trial of patients awaiting carotid endarterectomy . We r and omly allocated patients control , sunflower oil ( n-6 ) , or fish-oil ( n-3 ) capsules until surgery . Primary outcome was plaque morphology indicative of stability or instability , and outcome measures were concentrations of EPA , DHA , and linoleic acid in carotid plaques ; plaque morphology ; and presence of macrophages in plaques . Analysis was per protocol . FINDINGS 188 patients were enrolled and r and omised ; 18 withdrew and eight were excluded . Duration of oil treatment was 7 - 189 days ( median 42 ) and did not differ between groups . The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control ( absolute difference 0.5 [ 95 % CI 0.3 - 0.7 ] , 0.4 [ 0.1 - 0.6 ] , and 0.2 [ 0.1 - 0.4 ] g/100 g total fatty acids for EPA ; and 0.3 [ 0.0 - 0.8 ] , 0.4 [ 0.1 - 0.7 ] , and 0.3 [ 0.1 - 0.6 ] g/100 g total fatty acids for DHA ; in plaque phospholipids , cholesteryl esters , and triacylglycerols , respectively ) . Sunflower oil had little effect on the fatty acid composition of lipid fractions . Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation , compared with plaques in patients in the control and sunflower oil groups ( odds ratio 0.52 [ 95 % CI 0.24 - 0.89 ] and 1.19 [ 1.02 - 1.57 ] vs control ; 0.49 [ 0.23 - 0.90 ] and 1.16 [ 1.01 - 1.53 ] vs sunflower oil ) . The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups . Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups . INTERPRETATION Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation , inducing changes that can enhance stability of atherosclerotic plaques . By contrast , increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here . Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake BACKGROUND Fish oils have been shown to reduce production of tumor necrosis factor-alpha ( TNF-alpha ) in healthy subjects . We sought to evaluate the effects of fish oils on pro-inflammatory cytokines and body weight in patients with advanced heart failure . METHODS Fourteen patients ( New York Heart Association [ NYHA ] Class III to IV heart failure ) were r and omized in a double-blinded trial to active therapy with 8 g of n-3 fatty acids ( Group A , n = 7 ) or placebo ( Group B , n = 7 ) for 18 weeks . TNF-alpha and interleukin-1 ( IL-1 ) production were measured by radioimmunoassay after endotoxin stimulation of peripheral blood mononuclear cells . RESULTS Placebo-treated patients had a 44 % increase in TNF-alpha ( from 1.28 to 1.84 pg/ml ; p = 0.07 ) but no significant change in IL-1 ( from 0.68 to 0.78 pg/ml ) production . n-3 fatty acids result ed in a 59 % reduction in TNF-alpha ( from 1.64 to 0.68 pg/ml ; p = 0.02 ) and 39 % decrease in IL-1 ( from 1.98 to 1.21 pg/ml ; p = 0.09 ) production . There was an inverse correlation between change in TNF-alpha production and change in percent body fat ( r = -0.6 ; p = 0.02 ) . CONCLUSIONS Fish oils decrease TNF-alpha production in heart failure and improve body weight .  Fish oil therapy may represent a novel therapeutic approach in late-stage heart failure characterized by cardiac cachexia OBJECTIVE To determine the effects of n-3 PUFAs supplementation on plasma indices of coagulation ( fibrinogen ) , fibrin D-Dimer ( an index of thrombogenesis and fibrin turnover ) , endothelial damage/dysfunction ( von Willebr and factor ( vWf ) ) , platelet activation ( soluble P-selectin ( sP-sel ) ) and inflammation ( interleukin-6 , IL-6 ) in patients following acute myocardial infa rct ion . METHODS Open-labelled r and omised controlled trial . Seventy-seven post-myocardial infa rct ion ( MI ) patients stabilized on st and ard secondary prevention therapy were r and omised either to 3 months ' treatment with Omacor 1 g/day ( n=37 ) or ' usual care ' control ( n=40 ) . Plasma levels of fibrinogen , D-Dimer , vWf , sP-sel , IL-6 and plasma viscosity at baseline and after 3 months were determined . RESULTS At baseline , there were no significant differences between the groups in all research indices , except vWf levels were higher in patients allocated to Omacor supplementation . After 3 months , there were no significant changes in the levels of any research indices in either the Omacor supplemented or the ' usual care ' control patients when compared to baseline . Patients who received Omacor experienced a fall in total cholesterol ( p=0.019 ) , total/HDL-cholesterol ratio ( p=0.009 ) and LDL-cholesterol ( p=0.023 ) . However , the relative changes in plasma lipids and lipoproteins did not differ between the two groups . CONCLUSIONS Three-month supplementation of Omacor at 1 g per day in post-MI patients is not associated with an improvement in the levels of peripheral indices of coagulation potential , endothelial function , platelet reactivity and inflammation AIM To test whether the use of collagen matrix seal ( CMS ) results in similar hard and soft tissue remodelling to that with collagen sponge ( CS ) used as barriers 4 months following alveolar ridge preservation ( ARP ) , in combination with freeze-dried bone allograft ( FDBA ) . MATERIAL S AND METHODS Twenty-eight patients were r and omly assigned to the two groups . Clinical and radiographic measurements were recorded with the same stent at baseline and 4 months for st and ardization . The flapless technique following a traumatic extraction was used for the two types of barriers . RESULTS All patients completed the study , 14 in the CMS group and 14 in the CS group . Reduction in coronal ridge width ( 1.21 mm-14.91 % CMS and 1.47 mm-20.40 % CS ) and vertical buccal bone resorption ( 0.30 mm CMS and 0.79 mm CS ) were not significantly different . A slight increase in buccal gingival thickness at the coronal part was observed in both groups ( 0.9 mm CMS and 0.5 mm CS ) . CONCLUSIONS Collagen matrix seal and CS , when combined with FDBA , significantly minimized ridge resorption in all dimensions and maintained buccal soft tissue thickness in sockets with a buccal plate loss of < 2 mm in comparison to previously reported findings recorded after tooth extraction without ARP 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 The aim of this study was to evaluate the effects of a fish oil preparation ( MaxEPA ) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic ( NIDDM ) subjects . Eighty NIDDM out patients aged 55.9 yr ( mean SD 11.5 yr ) participated in a prospect i ve double-blind placebo-controlled study of MaxEPA capsules ( 10 g/day ) or olive oil ( control ) treatment over 6 wk . Patients received either MaxEPA or olive oil in addition to preexisting therapy .  Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk . Platelet membrane eicosapentaenoic acid ( EPA ) content increased in the treatment group ( P < 0.001 ) . MaxEPA supplementation was associated with a significant fall in total triglycerides ( P < 0.001 ) but did not affect total cholesterol ( P = 0.7 ) compared with control treatment . Fasting plasma glucose increased after 3 wk ( P = 0.01 ) but not after 6 wk ( P = 0.17 ) treatment with MaxEPA .  Spontaneous platelet aggregation in whole blood fell in the MaxEPA group ( P < 0.02 ) after 6 wk , but there were no changes in agonist-induced platelet aggregation , thromboxane generation in platelet-rich plasma , or plasma P-thromboglobulin and platelet factor IV levels . An increase in clotting factor VII ( P = 0.02 ) , without changes in fibrinogen or factor X levels , occurred in the MaxEPA group . Similar reductions in blood pressure were observed in both groups . Dietary supplementation with MaxEPA capsules ( 10 g/day ) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels . Most indices of platelet function are unaffected by this therapy Aims To assess the bone dimensional changes after  extraction and alveolar ridge preservation ( ARP ) using primary coverage ( closed flap technique , CFT ) or healing by secondary intention ( open flap technique , OFT ) . Material s and Methods Ten patients ( split mouth design ) were planned for extraction and ARP . All sites received ARP with freeze-dried bone allograft ( FDBA ) and nonresorbable membrane after extraction . Clinical st and ardized measurements were used to assess the dimensional alterations of the alveolar ridge . Results All patients completed the study , and a total of 20 sites were r and omized to CFT or OFT group . Center height ( mean difference of 8.1 mm , SD = 1.9 CFT , and 7.5 mm , SD= 1.8 OFT ) and buccal height ( mean difference of 0.8 mm , SD = 1.0 CFT , and 0.3 mm , SD= 1.1 OFT ) were significantly different within the same group . However , there was no statistically significant difference between groups . In the OFT group , the keratinized tissue width was higher and the pain VAS scores at 24 hours were lower compared with the CFT ( p = 0.004 and p = 0.006 , respectively ) . Conclusions Leaving the flap open did not have any effects on the dimensional changes of bone height or width . However , there was a wider b and of keratinized tissue and less pain with the CFT compared with the OFT . The study protocol was registered at Clinical Trials.gov , Identifier NCT03136913
target: We conclude that omega-3 fatty acids may be associated with lower inflammatory biomarkers among diabetic and cardiovascular patients .
background: The purpose of this systematic review and meta- analysis was to investigate omega-3 fatty acids ’ influence on 12 inflammatory biomarkers — LDL , HDL , total cholesterol , TG , HbA1c , Apo AI , Apo AII , Apo B , CRP , TNF-α , glucose , and fasting blood glucose among diabetic and cardiovascular disease ( CVD ) patients .