Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. Effect of w3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial N-3 fatty acids do not lead to an increased diabetic risk in patients with hyperlipidemia and abnormal glucose tolerance. Italian Fish Oil Multicenter Study. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans. The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Fish and Long-Chain &ohgr;-3 Fatty Acid Intake and Risk of Coronary Heart Disease and Total Mortality in Diabetic Women [The effect of fish oil on the secretion and effect of insulin in patients with type II diabetes]. Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. A Comparison of the Effects of n-3 Fatty Acids From Linseed Oil and Fish Oil in Well-Controlled Type II Diabetes Variable Hypocoagulant Effect of Fish Oil Intake in Humans: Modulation of Fibrinogen Level and Thrombin Generation Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives. Predicting sudden death in the population: the Paris Prospective Study I. Fish Consumption Is Associated With Lower Heart Rates Effect of Fish Oil Concentrate on Lipoprotein Composition in NIDDM Hemostatic Factors as Predictors of Coronary Events and Total Mortality: The FINRISK ’92 Hemostasis Study Dietary fish oil augments nitric oxide production or release in patients with Type 2 (non-insulin-dependent) diabetes mellitus Effects of a Small Quantity of ω-3 Fatty Acids on Cardiovascular Risk Factors in NIDDM: A randomized, prospective, double-blind, controlled study Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia. A Comparison of Fish Oil or Corn Oil Supplements in Hyperlipidemic Subjects with NIDDM Implications of small reductions in diastolic blood pressure for primary prevention. Effects of a fish oil supplement on platelet function, haemostatic variables and albuminuria in insulin-dependent diabetics. Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus. Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men. Supplementation with n‐3 fatty acids reduces triglycerides but increases PAI‐1 in non‐insulin‐dependent diabetes mellitus Population-based incidence rates and risk factors for type 2 diabetes in white individuals: the Bruneck study. Coagulation factor VII and the risk of coronary heart disease in healthy men. Long-Term Effects of Fish Oil on Insulin Resistance and Plasma Lipoproteins in NIDDM Patients With Hypertriglyceridemia Effects of low-dose omega-3 fatty acid substitution in type-2 diabetes mellitus with special reference to oxidative stress--a prospective preliminary study. 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
In a double-blind , placebo-controlled study we investigated the effects of dietary fish oil supplementation on arterial wall characteristics in 20 patients with non-insulin-dependent diabetes mellitus . Estimates reflecting compliance values in the large arteries and more peripheral vasculature , as measured by pulse-contour analysis , improved significantly after 6 weeks of fish oil therapy compared with values recorded at baseline and after 6 weeks ' administration of olive oil . The large-artery compliance estimate increased from 1.50 ( confidence interval [ CI ] , 1.31 to 1.69 ) mL/mm Hg at baseline to 1.68 ( CI , 1.52 to 1.84 ) mL/mm Hg after fish oil administration ( P < .01 ) . The oscillatory compliance value increased from 0.015 ( CI , 0.011 to 0.019 ) mL/mm Hg at baseline to 0.022 ( CI , 0.016 to 0.028 ) mL/mm Hg after fish oil ingestion ( P < .05 ) . No changes occurred in arterial blood pressure , cardiac output , stroke volume , or systemic vascular resistance with either intervention . The improved compliance estimates with fish oil ingestion occurred without altering fasting blood glucose and cholesterol concentrations . These results support the hypothesis that fish oils alter vascular reactivity and favorably influence arterial wall characteristics in patients with non-insulin-dependent diabetes mellitus . These direct vascular effects , expressed at the level of the vessel wall , may contribute to the cardioprotective actions of fish oil in humans Objective : Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus . However , fish oil may have deleterious effects on lipid peroxidation and glycemic control . Design : In this study , 44 type 2 diabetic patients were r and omized to vitamin E st and ardized ( 53.6 mg/day ) supplementation ( capsules ) with 4 g daily of either fish oil ( n=23 ) or corn oil ( n=21 ) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation . LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu2 + . As a marker of in vivo oxidation malondialdehyde concentration in LDL ( LDL-MDA ) was measured . Results : Fish oil reduced both mean lag time ( before , 57.8 ; after , 48.8 min , P<0.001 ) and mean propagation rate ( before , 0.018 ΔOD/min ; after , 0.015 ΔOD/min , P<0.001 ) , whereas corn oil had no influence on lag time and propagation rate . The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment . LDL-MDA changes differed borderline significantly between groups ( FO , 110.4 pmol/mg protein ; CO , 6.7 pmol/mg protein ; P=0.057 ) . Fish oil supplementation had no influence on glycemic control as assessed from HbA1c and fasting blood glucose . Conclusion : According to our findings , fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles . More studies are needed to clarify the clinical importance of this finding . Sponsorship : Financially supported by The Danish Heart Association and Dansk Droge A/S. Dansk Droge A/S generously provided the fish oil and corn oil capsules Modification of dietary fat composition may influence hemostatic variables , which are associated with increased risk of coronary heart disease ( CHD ) . To address this question , we performed a controlled feeding study on 26 healthy male nonsmoking subjects with diets of differing fat composition . For the first 3 weeks , the subjects were given a diet calculated to supply 30 % energy as total fat : 8 % as monounsaturated , 4 % as polyunsaturated , and 16 % energy as saturated fatty acids , respectively ( saturated diet ) . This was followed immediately by two diets taken in r and om order , each of 3-week duration and separated by an 8-week washout period on the subject 's usual diet . Both diets were calculated to supply 30 % of energy as fat : 14 % monounsaturated , 6 % as polyunsaturated , and 8 % energy as saturated fatty acids . They both provided 5 g ( approximately 1.7 % energy ) more of polyunsaturated fatty acids than the saturated fat diet ; in one diet as long-chain n-3 fatty acids ( n-3 diet ) and in the other as linoleic acid ( n-6 diet ) .  Fasting plasma lipids , lipoproteins , and hemostatic factors were measured on the final 3 days of each dietary period . In a subset of 9 subjects the postpr and ial responses to a test meal were studied on the penultimate day of each period , each meal having the fat composition of its parent diet . On the n-3 diet compared with the n-6 diet , plasma triglyceride , HDL3 cholesterol , apoprotein AII , and fibrinogen concentrations were lower and HDL2 cholesterol concentration was higher ( P = .0001 , P = .003 , P = .0001 , P = .004 , and P = .001 , respectively ) . On both the n-3 and n-6 diets compared with the saturated diet , fasting plasma total and LDL cholesterol , apoprotein B , beta-thromboglobulin concentrations , and platelet counts were lower ( P < .0001 , P < .0001 , P < .001 , P < .01 , and P < .05 respectively ) and plasma Lp(a ) and von Willebr and factor concentrations were higher ( P = .02 and P < .01 , respectively ) . Fasting factor VII coagulant activity ( VIIc ) was increased and apoprotein AI concentration reduced following the n-3 diet ( P = .004 and P = .01 , respectively ) compared with the saturated diet . Plasma fibrinogen concentration was significantly greater following the n-6 diet than on the saturated diet ( P = .02 ) . Postpr and ially , plasma triglyceridemia was greater on the n-6 diet and lowest on the n-3 diet ( P < .001 ) with the saturated diet being intermediate . Plasma VIIc was increased at 4 hours following the st and ardized test meals on the n-3 and n-6 diets ( both P < .05 ) but not on the saturated diet . An increased intake of long chain n-3 fatty acids decreases fasting plasma triglyceride and apoprotein AII concentrations and increases HDL2 cholesterol concentrations and results in less postpr and ial lipemia but leads to an increase in VIIc . An increased intake of linoleic acid may raise plasma fibrinogen concentration . Decreasing the intake of saturated fatty acids reduces plasma LDL cholesterol and apoprotein B without affecting HDL cholesterol concentration independent of the type of polyunsaturated fatty acids in the diet . When advice is given to reduce saturated fat intake , it is important to ensure an appropriate ratio of n-3/n-6 fatty acids in the diet Summary This study was conducted to examine the effect of ω3 fatty acid supplementation on plasma lipid , cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher ( 0.65 , n = 10 ) or lower ( 0.44 , n = 18 ) ratio of dietary polyunsaturated to saturated fatty acid ( P/S ) . The participants were initially given an olive oil supplement ( placebo ) equivalent to 35 mg of 18:1 · kg body weight–1 · day–1 for 3 months . This was followed by two ω3 supplement periods in a r and omized crossover . In these 3-month periods , participants were given a linseed oil supplement equivalent to 35 mg of 18:3ω3 · kg body weight–1 · day–1 or a fish oil supplement equivalent to 35 mg of 20:5ω3 + 22:6ω3 · kg body weight–1 · day–1 . At the end of each supplement period , a blood sample was drawn from each participant for lipid , lipoprotein , insulin , glucagon and C-peptide analyses . At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio . Results indicate that fish oil significantly reduced plasma triacylglycerol level ( p < 0.05 ) and increased 20:5ω3 and 22:6ω3 content of all lipoprotein lipid classes . Linolenic acid supplementation had no effect on plasma triacylglycerol level , but it increased 18:3ω3 content of lipoprotein cholesterol ester fractions ( p < 0.05 ) . A slight increase in 20:5ω3 , but not 22:6ω3 , content was noted in lipoprotein lipid classes as a result of 18:3ω3 supplementation . LDL and HDL cholesterol , insulin , glucagon and C-peptide levels were not affected by either ω3 supplement . It is concluded that a modest intake of ω3 fatty acids , such as could be obtained from consuming fish regularly , will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels . [ Diabetologia ( 1997 ) 40 : 45–52 BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration A multicenter , r and omized , double-blind , place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes . A total of 935 patients of both sexes in 63 Italian clinical centers were selected ; 55 % had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus ( NIDDM ) . They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo , followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo . In addition to the complete lipid and lipoprotein evaluation , patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test ; in patients with NIDDM , serum insulin and glycated hemoglobin ( Hb A1c ) concentrations were determined . Plasma triacylglycerol concentrations decreased significantly , up to 21.53 % at 6 mo compared with baseline ( decreased 15 % compared with placebo ) , with a tendency toward a progressive reduction with time . There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance . Among NIDDM patients , the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes : fasting glucose , Hb A1c , insulinemia , and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters . Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation BACKGROUND n-3 Fatty acids lower blood pressure , improve lipids , and benefit other cardiovascular disease risk factors . Effects on glycemia in patients with type 2 diabetes are uncertain . OBJECTIVE We determined whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) have differential effects on glycemic control , including insulin sensitivity and stimulated insulin secretion ; 24-h ambulatory blood pressure ; and serum lipids in type 2 diabetic patients with treated hypertension . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 subjects were r and omly assigned to consume 4 g EPA , DHA , or olive oil/d for 6 wk while continuing to consume their usual diet . RESULTS Thirty-nine men and 12 postmenopausal women with a mean ( + /- SE ) age of 61.2 + /- 1.2 y completed the study . In comparison with the change from baseline in fasting glucose in the olive oil group , fasting glucose in the EPA and DHA groups increased 1.40 + /- 0.29 mmol/L ( P = 0.002 ) and 0.98 + /- 0.29 mmol/L ( P = 0.002 ) , respectively . Neither EPA nor DHA had significant effects on glycated hemoglobin , fasting insulin or C-peptide , insulin sensitivity or secretion , or blood pressure . Serum triacylglycerols in the EPA and DHA groups decreased 19 % ( P = 0.022 ) and 15 % ( P = 0.022 ) , respectively . There were no significant changes in serum total , LDL , or HDL cholesterol , although HDL(2 ) cholesterol in the EPA and DHA groups increased 16 % ( P = 0.026 ) and 12 % ( P = 0.05 ) , respectively . HDL(3 ) cholesterol decreased 11 % ( P = 0.026 ) with EPA supplementation . CONCLUSIONS EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients . The overall implication s for cardiovascular disease require long-term evaluation BACKGROUND Higher intakes of fish and n-3 fatty acids are associated with a reduced risk of cardiovascular events and mortality . However , limited data exist on the effect of fish intake on actual measures of progression of coronary artery atherosclerosis . OBJECTIVE The aim was to examine the association between fish intake and the progression of coronary artery atherosclerosis in women with coronary artery disease . DESIGN This was a prospect i ve cohort study of postmenopausal women ( n = 229 ) participating in the Estrogen Replacement and Atherosclerosis trial . Usual fish intake was estimated at baseline with a food-frequency question naire . Quantitative coronary angiography was performed at baseline and after 3.2 + /- 0.6 ( x + /- SD ) y to evaluate changes in the mean minimum coronary artery diameter , the mean percentage of stenosis , and the development of new coronary lesions . RESULTS Compared with lower fish intakes , consumption of > or = 2 servings of fish or > or = 1 serving of tuna or dark fish per week was associated with smaller increases in the percentage of stenosis ( 4.54 + /- 1.37 % compared with -0.06 + /- 1.59 % and 5.12 + /- 1.48 % compared with 0.35 + /- 1.47 % , respectively ; P < 0.05 for both ) in diabetic women after adjustments for age , cardiovascular disease risk factors , and dietary intakes of fatty acids , cholesterol , fiber , and alcohol . These associations were not significant in nondiabetic women . Higher fish consumption was also associated with smaller decreases in minimum coronary artery diameter and fewer new lesions . CONCLUSIONS Consumption of fish is associated with a significantly reduced progression of coronary artery atherosclerosis in women with coronary artery disease Dietary alpha-linolenic acid ( ALA ) can be converted to long-chain ( n-3 ) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids on risk factors for coronary heart disease ( CHD ) . This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects . A placebo-controlled , parallel study was conducted in 150 moderately hyperlipidemic subjects , age 25 - 72 y. Subjects were r and omly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA , 4.5 or 9.5g/d ALA or control ( linoleic acid ; LA ) for 6 mo . Fatty acids were incorporated into 25 g of fat spread , which replaced the subject 's normal spread and three capsules . Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa , VIIc , VIIag , XIIa , XIIag , fibrinogen concentrations , plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control . ( n-3 ) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat , high complex carbohydrate diet .  Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation ;  plasma total and HDL cholesterol concentrations did not change . The LDL cholesterol level was significantly increased with fish oil supplementation , suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and /or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease . The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Background —Although several prospect i ve cohort studies have found an inverse association between fish consumption and risk of coronary heart disease ( CHD ) or sudden cardiac death in the general population , limited data are available among diabetic patients . Methods and Results —We examined prospect ively the association between intake of fish and & ohgr;-3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline . Between 1980 and 1996 ( 45 845 person-years of follow-up ) , we documented 362 incident cases of CHD ( 141 CHD deaths and 221 nonfatal myocardial infa rct ions ) and 468 deaths from all causes . Compared with women who seldom consumed fish ( < 1 serving/mo ) , the relative risks ( RRs ) ( 95 % CI ) of CHD adjusted for age , smoking , and other established coronary risk factors were 0.70 ( 0.48 to 1.03 ) for fish consumption 1 to 3 times per month , 0.60 ( 0.42 to 0.85 ) for once per week , 0.64 ( 0.42 to 0.99 ) for 2 to 4 times per week , and 0.36 ( 0.20 to 0.66 ) for 5 or more times per week ( P for trend=0.002 ) . Higher consumption of fish was also associated with a significantly lower total mortality ( multivariate RR=0.48 [ 0.29 to 0.80 ] for ≥5 times per week [ P for trend=0.005 ] ) . Higher consumption of long-chain & ohgr;-3 fatty acids was associated with a trend toward lower incidence of CHD ( RR=0.69 [ 95 % CI 0.47 to 1.03 ] , P for trend=0.10 ) and total mortality ( RR=0.63 [ 95 % CI , 0.45 to 0.88 ] , P for trend=0.02 ) . Conclusions —A higher consumption of fish and long-chain & ohgr;-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women The metabolic effect of 3-week dietary supplementation with a fish oil concentrate was examined in not markedly obese , not hypertriglyceridemic men with non-insulin-dependent diabetes mellitus ( NIDDM ) treated with hypoglycemic agents . Ten patients were given 15 ml/d of fish oil ( Martens Oil , Norway ) equivalent to 3.1 g of n-3 fatty acid ( FA ) per day , and compared to 10 diabetics treated with placebo ( 15 ml/d saline ) . While fish oil leads to expected increase in the ratio of n-3 to n-6 FA intake , it does not alter fasting and mixed meal stimulated blood glucose , plasma insulin and C-peptide concentrations . There were no changes in insulin action estimated by the metabolic clearance rates of glucose at plasma insulin levels of about 100 microU/ml and 1400 microU/ml during hyperinsulinemic isoglycemic clamp , and no changes were seen in insulin binding to erythrocytes . Even though our short-term study does not warrant authoritative conclusions , no adverse effects of low-dose fish oil on glucose homeostasis have been found in not markedly obese NIDDM patients treated with oral hypoglycemics OBJECTIVE The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol ( TAG ) , low HDL cholesterol , and a predominance of atherogenic small dense LDLs . Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might , therefore , be a good nonpharmacological treatment for type 2 diabetic patients . In the present study , we investigate the effect of fish oil supplementation on the fasting lipid profile , including LDL and HDL subclasses . RESEARCH DESIGN AND METHODS A total of 42 type 2 diabetic patients were r and omized to supplementation ( capsules ) with 4 g daily of either fish oil ( n = 20 ) or corn oil ( n = 22 ) for 8 weeks preceded by a 4-week run-in period of corn oil supplementation . Blood was drawn before and after the 8-week intervention period . Plasma lipoproteins , including LDL and HDL subclasses , were separated by ultracentrifugation . RESULTS Fish oil lowered TAG ( group difference : P = 0.025 ) and raised HDL-2b cholesterol ( P = 0.012 ) and HDL-2a cholesterol ( P = 0.007 ) concentrations as compared with corn oil . We observed no significant effects of fish oil on LDL cholesterol , HDL cholesterol , or the concentration of small dense LDL particles . CONCLUSIONS Fish oil supplementation may partially correct the dyslipidemia of type 2 diabetic patients . However , the putative very important aspect of diabetic dyslipidemia-the predominance of small dense LDL particles-was unaffected by fish oil OBJECTIVE Supplementation of type II diabetic diets with n-3 fatty acids ( FAs ) from fish oil ( FO ) has been associated with lowered triglyceride and VLDL levels , although reports of impaired glycemic control have limited their use . Effects of n-3FAs from nonmarine sources are less well documented . Therefore , an investigation comparing the effects of linseed oil ( LO ) with FO supplementation was undertaken in subjects with type II diabetes . RESEARCH DESIGN AND METHODS Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a r and omized double-blind crossover fashion after 3 months of olive oil placebo . Oils were given as 35 mg FA · kg body wt−1 · day−1 . After each 3-month period , fasting glucose and insulin levels , HbA1c , lipid profiles , insulin sensitivity ( SI ) , glucose effectiveness ( SG ) , and acute insulin response to glucose ( AIRG ) were evaluated . RESULTS HbA1c and lipid values were within the normal range at r and omization . Repeated measures analysis of variance testing found no significant differences in weight ; fasting glucose and insulin levels ; HbA1c ; total , LDL , and HDL cholesterol levels ; SI ; SG ; or AIRG with either active oil . FO was associated with significant reductions in triglycerides and a trend toward decreased SI . CONCLUSIONS In a population with well-controlled type II diabetes , 3 months of FO but not LO result ed in lowered triglyceride levels . Neither LO nor FO significantly affected glycemic control , cholesterol values , SG , or insulin secretion , while a nonsignificant trend toward decreased insulin sensitivity was found with FO Objective —The beneficial effect of dietary fish oil , rich in omega-3 polyunsaturated fatty acids ( PUFAs ) , on cardiovascular disease is multifactorial and may partly rely on their anticoagulant action . We studied how fish oil intake influenced thrombin generation in plasma and which factors were involved herein . Methods and Results —Twenty-five healthy males with borderline overweight received 3.0 g omega-3 PUFAs daily for 4 weeks . Fish oil intake reduced plasma triglycerides and lowered platelet integrin activation , as well as plasma levels of fibrinogen and factor V , but had no effect on vitamin K-dependent coagulation factors . Before fish oil intake , thrombin generation ( reflecting the coagulant potential ) considerably varied between plasmas from individual subjects , which were partly explained by variation in prothrombin , antithrombin , fibrinogen , and factor V levels . Fish oil intake reduced thrombin generation in the presence and absence of platelets . This reduction correlated with the fish oil effect on fibrinogen and factor V levels . Interestingly , the lowering effect of fish oil on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying a structural fibrinogen α-chain polymorphism . Conclusions —Dietary omega-3 PUFAs provoke a hypocoagulant , vitamin K-independent effect in humans , the degree of which may depend on fibrinogen level Obesity is a major factor contributing to hypertension and increased risk of cardiovascular disease . Regular consumption of dietary fish and omega3 fatty acids of marine origin can lower blood pressure ( BP ) levels and reduce cardiovascular risk . This study examined the potential effects of combining dietary fish rich in omega3 fatty acids with a weight loss regimen in overweight hypertensive subjects , with ambulatory BP levels  as the primary end point . Using a factorial design , 69 overweight medication-treated hypertensives were r and omized to a daily fish meal ( 3.65 g omega3 fatty acids ) , weight reduction , the 2 regimens combined , or a control regimen for 16 weeks .  Sixty-three subjects with a mean+/-SEM body mass index of 31.6+/-0.5 kg/m2 completed the study .  Weight fell by 5.6+/-0.8 kg with energy restriction . Dietary fish and weight loss had significant independent and additive effects on 24-hour ambulatory BP . Effects were greatest on awake systolic and diastolic BP ( P<0.01 ) ; relative to control , awake pressures fell 6.0/3.0 mm Hg with dietary fish alone , 5.5/2.2 mm Hg with weight reduction alone , and 13.0/9.3 mm Hg with fish and weight loss combined . These results also remained significant after further adjustment for changes in urinary sodium , potassium , or the sodium/potassium ratio , as well as dietary macronutrients . Dietary fish also significantly reduced 24-hour ( -3.1+/-1.4 bpm , P=0.036 ) and awake ( -4.2+/-1.6 bpm , P=0 . 013 ) ambulatory heart rates . Weight reduction had a significant effect on sleeping heart rate only ( -3.2+/-1.7 bpm , P=0.037 ) . Combining a daily fish meal with a weight-reducing regimen led to additive effects on ambulatory BP and decreased heart rate . The effects were large , suggesting that cardiovascular risk and antihypertensive drug requirements are likely to be reduced substantially by combining dietary fish meals rich in omega3 fatty acids with weight-loss regimens in overweight medication-treated hypertensives . The reduction in heart rate seen with dietary fish suggests a cardiac/autonomic component , as well as vascular effects , of increased consumption of omega3 fatty acid from fish BACKGROUND Sudden death was found to share the same set of usual risk factors as coronary events and therefore could not be specifically predicted in the population . It appears , however , that parental history of sudden death has not been investigated yet as a risk factor for sudden death . Therefore , we assessed risk factors , including parental sudden death , associated with the occurrence of sudden death in a long-term cohort study . METHODS AND RESULTS We included 7746 men employed by the city of Paris who were 43 to 52 years of age in 1967 to 1972 in the Paris Prospect i ve Study I. Each subject underwent a physical examination and an ECG , provided blood for laboratory tests , and answered question naires administered by trained interviewers who paid particular attention to family medical history .  Men with known ischemic cardiac disease were further excluded from analysis . For 95.5 % of the men , vital status was obtained from specific inquiries until retirement , then by death certificates . Resting heart rate , systolic or diastolic blood pressure , tobacco consumption , body mass index , diabetes status , serum cholesterol , and parental history of sudden death were independent factors associated with sudden death during follow-up ( 23 years on average ) . When adjusted for confounding variables , including parental history of myocardial infa rct ion , relative risk of sudden death associated with parental sudden death was 1.80 ( 95 % CI , 1.11 to 2.88 ) . CONCLUSIONS Parental sudden death is an independent risk factor for sudden death in middle-aged men . The existence of familial risk factors for sudden death may help provide better identification of subjects at high risk of and early prevention of sudden death Background —Fish consumption decreases risk of sudden death . The goal of the present study was to assess the relationship between fish consumption and heart rate . Methods and Results —A cross-sectional analysis was conducted of 9758 men , age 50 to 59 years , without coronary heart disease ( CHD ) who were recruited in France and Belfast , Irel and , from 1991 to 1993 .  Heart rate and CHD risk factors were compared among 4 categories of fish consumption , as follows : ( 1 ) less than once per week ( n=2662 ) , ( 2 ) once per week ( n=4576 ) , ( 3 ) twice per week ( n=1964 ) , and ( 4 ) more than twice per week ( n=556 ) . Fatty acid profiles of erythrocyte phospholipids were determined in a r and om sub sample of 407 subjects . In erythrocyte phospholipids , eicosapentaenoic acid ( P < 0.0005 ) , docosahexaenoic acid ( P < 0.0001 ) , and total n-3 fatty acid ( P < 0.0008 ) increased across the categories of fish intake . Triglycerides ( P < 0.0001 ) , systolic blood pressure ( P < 0.006 ) , and diastolic blood pressure ( P < 0.0001 ) were lower and HDL cholesterol levels ( P < 0.004 ) were higher in fish consumers than in nonconsumers . Similarly , heart rate decreased across the categories of fish intake ( P < 0.0001 ) . After adjustment for age , center , education level , physical activity , smoking habit , alcohol consumption , body mass index , and antiarrhythmic medications , heart rate remained statistically lower among fish consumers than among nonconsumers ( P for trend < 0.0001 ) . Docosahexaenoic acid content of erythrocyte phospholipids was inversely correlated with heart rate ( P < 0.03 ) . Conclusions —Fish consumption is associated with decreased heart rate in men . Because heart rate is positively associated with risk of sudden death , this association may explain , at least in part , the lower risk of sudden death among fish consumers Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with elevated very-low-density lipoprotein ( VLDL ) triglyceride concentrations and abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects , we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM .  Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design . Medications , including antidiabetic therapy , were continued through the study . Compared with safflower oil treatment , fish oil supplementation result ed in a significant reduction of total plasma triglycerides of 24 % at the 4-g dose and a larger reduction of 39 % at the 7.5-g dose . These decreases were due to similar reductions in VLDL triglycerides . LDL cholesterol levels were mildly elevated , but a larger 20 % increase in LDL apolipoprotein B ( apoB ) concentration was observed . During supplementation with the fish oil concentrate , the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values , but not when compared with safflower oil treatment .  Highdensity lipoprotein ( HDL ) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment . At the 7.5-g dose , fasting glucose and glycohemoglobin levels increased by 20 and 12 % , respectively , but were unchanged at the lower level of supplementation . Thus , in NIDDM patients , dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels . However , the observed increase in LDL apoB levels , and the deterioration in glycemic control , indicate thatfurther study will be required to establish whether fish oil has a role in the treatment of NIDDM The role of hemostatic factors as predictors of coronary heart disease ( CHD ) and total mortality is poorly understood . Therefore , we carried out a prospect i ve cohort study in Finl and . In 1992 , a r and om population sample of 2378 men and women aged 45 to 64 years was investigated and then followed up until December 31 , 1998 . During the follow-up , 133 CHD events were observed ; 73 were among participants free of CHD at baseline . The total number of deaths was 124 . After adjustment for traditional risk factors and prevalent CHD at baseline and correction for regression dilution bias , a 1-SD increase in plasminogen was associated with a 1.41-fold ( 95 % CI 1.09 to 1.81 ) increase in CHD risk . The predictive power of plasminogen depended significantly on the level of total cholesterol being stronger for persons with high cholesterol . A 1-SD increase in fibrinogen was associated with a 1.23-fold ( 95 % CI 1.05 to 1.44 ) increase in all-cause mortality , but its association with CHD events did not reach statistical significance . Factor VII antigen or coagulant activity or lipoprotein(a ) were not independent predictors of CHD risk . These findings support the role of plasminogen as a risk factor for CHD events Summary Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease . Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations , principally by improving the release of nitric oxide from injured endothelium . Using forearm venous occlusion plethysmography we studied vascular responses to 60 , 120 , 180 and 240 nmol/min of acetylcholine ( an endothelium-dependent vasodilator ) and 3 , 6 and 9 nmol/min of glyceryl trinitrate ( an endothelium-independent vasodilator ) infused into the brachial artery in 23 patients with Type 2 ( non-insulin-dependent ) diabetes mellitus . NG monomethyl-l-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the active treatment periods at 6 and 18 weeks . Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration ( p<0.01 ) . Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies . NG monomethyl-l-arginine significantly reduced forearm blood flow from maximal stimulated values to acetylcholine when compared to the uninhibited decline in flow to acetylcholine infusions at comparable time points ( p<0.01 ) . Treatment with fish oils improved endothelium-dependent responses to acetylcholine without altering endothelium-independent responses to glyceryl trinitrate . By increasing stimulated nitric oxide release from the endothelium fish oils may afford protection against vasospasm and thrombosis in patients with diabetes mellitus OBJECTIVE To study the effects of a low dose of ω-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellus ( NIDDM ) . RESEARCH DESIGN AND METHODS We performed a r and omized , prospect i ve , double-blind , controlled study of a low dose of ω-3 fatty acids ( 2.5 g/day ) in 20 ambulatory subjects with NIDDM . Subjects ingested five 1-g fish oil capsules each containing 0.5 g ω-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period . RESULTS Nine subjects completed the study in each group . Both groups exhibited moderate control of glucose levels ; modest elevations in baseline total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglyceride ( TG ) levels ; and normal blood pressure values . In the fish oil group , plasma ω-3 fatty acid levels increased significantly . Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil . No difference was observed in collageninduced production of thromboxane A2 ( TXA2 , measured as the stable derivative TXB2 ) , or in adenosine-5'-diphosphate- ( ADP ) induced platelet aggregation or TXA2 generation . Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil . Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure ( sBP ) by 8 mmHg compared with safflower oil . Fish oil caused a significant but small increase in HbA1c ( 0.56 % ) and total cholesterol ( 20 mg/dl ) but had no effect on fasting glucose , high-density lipoprotein cholesterol , or LDL-cholesterol levels . CONCLUSIONS Small doses of fish oil inhibit platelet aggregation and TXA2 production , reduce upright sBP and TG levels , and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM . Small quantities of ω-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n-3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double-blind cross-over study during two consecutive 8-week periods . After MaxEPA treatment , there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids , while the n-6 fatty acid content decreased . The very low density lipoprotein ( VLDL ) triglyceride concentrations decreased significantly ( by 22 % ) on MaxEPA treatment . However , these changes were not significantly different from those observed during the placebo period . The blood glucose concentration tended to increase during MaxEPA treatment , and to decrease during the placebo period , the changes under the two regimes being significantly different ( P less than 0.01 ) . In addition , the rate constant for glucose disappearance ( k value ) for the intravenous insulin-tolerance test , which reflected the peripheral insulin sensitivity , tended to decrease during MaxEPA treatment and increase during administration of the placebo , there being a significant difference ( P less than 0.03 ) between the changes during the two treatments . The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear The effects of fish oil on lipoprotein subfractions and low density lipoprotein ( LDL ) size in non-insulin-dependent diabetes mellitus ( NIDDM ) patients with hypertriglyceridemia are unknown . To eluci date this , 16 NIDDM hypertriglyceridemic patients ( plasma triglyceride 2.25- 5.65 mmol/l , plasma cholesterol < or = 7.75 mmol/l ) were r and omly assigned to a 6-month period with either moderate amounts of fish oil ( n = 8) or placebo ( n = 8) after 4 weeks of wash-out and 3 weeks of run-in . Diet and hypoglycemic treatment were unchanged throughout the experiment . LDL size were evaluated at baseline and after 6 months . Three VLDL and LDL subfractions were measured at the end of the two periods . The total lipid concentration of all very low density lipoprotein ( VLDL ) subfractions was lower at the end of fish oil treatment compared with placebo ( large VLDL 124.3 + /- 19.7 mg/dl vs 156.7 + /- 45.5 mg/dl ; intermediate VLDL 88.5 + /- 9.5 mg/dl vs 113.9 + /- 23.2 mg/dl ; small VLDL 105.9 + /- 9.7 mg/dl vs 128.9 + /- 40.7 mg/dl ) ( mean + /- SEM ) , although the difference was not statistically significant . Moreover , at the end of the two treatments , the percentage distribution of VLDL subfractions was very similar ( large 37.5 + /- 3.3 % vs 37.6 + /- 2.6 % , intermediate 27.6 + /- 0.9 % vs 31.0 + /- 2.4 % ; small 34.9 + /- 3.7 % vs 31.4 + /- 2.1 % ) . Concerning LDL , no significant change in LDL size was observed after the two treatments ( 255.4 + /- 2.2 A vs 254.2 + /- 1.7 A , fish oil ; 253.7 + /- 2.0 A vs 253.3 + /- 1.7 A , placebo ) . LDL subfraction distribution was also very similar ( large 17 + /- 3 % vs 17 + /- 2 % ; intermediate 62 + /- 3 % vs 65 + /- 3 % ; small 21 + /- 3 % vs 18 + /- 2 % ) , at the end of the two periods , confirming the lack of effects on LDL size . In conclusion , our study indicates that in NIDDM patients with hypertriglyceridemia , fish oil does not induce any improvement in LDL distribution and LDL size despite its positive effects on plasma triglycerides OBJECTIVE To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Forty subjects ( 18 men and 22 women ; aged 53.9 ± 7.0 years ) with NIDDM and hyperlipidemia were r and omly assigned to one of four treatment groups : 9 g of fish oil , 18 g of fish oil , 9 g of corn oil , or 18 g of corn oil daily supplementation for 12 weeks . RESULTS The level of oil supplements ( 9 g compared with 18 g ) did not have a significant effect within each oil group on glycemic control and lipids . Significant differences ( P < 0.05 ) in lipids were found when the 9-g and 18-g groups were combined . In subjects consuming fish oil , plasma very-low-density lipoprotein ( VLDL ) cholesterol ( P = 0.0001 ) , plasma triglyceride ( TG ) ( P = 0.0001 ) , and plasma VLDL TGs ( P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks ) were significantly lowered compared with subjects consuming corn oil . Plasma VLDL cholesterol increased across time in the corn oil group ( P = 0.04 ) . Plasma low-density lipoprotein ( LDL ) cholesterol was temporarily increased ( P = 0.008 ) in the fish oil group at 6 weeks , but the effect was no longer present at 12 weeks . No significant differences between fish oil – or corn oil-supplemented diets were found in total plasma cholesterol , high-density lipoprotein cholesterol , fasting plasma glucose , glycosylated HbA1c , weight , and blood pressure . CONCLUSIONS In this study , fish oil supplementation improved plasma VLDL cholesterol , VLDL TGs , and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM . Furthermore , fish oil supplementation had no significant deleterious effect on glycemic control OBJECTIVES To estimate the impact of small reductions in the population distribution of diastolic blood pressure ( DBP ) , such as those potentially achievable by population -wide lifestyle modification , on incidence of coronary heart disease ( CHD ) and stroke . DESIGN Published data from the Framingham Heart Study , a longitudinal cohort study , and from the National Health and Nutrition Examination Survey II , a national population survey , were used to examine the impact of a population -wide strategy aim ed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects . SETTING / PARTICIPANTS White men and women aged 35 to 64 years in the United States . MAIN OUTCOME MEASURES Incidence of CHD and stroke , including transient ischemic attacks ( TIAs ) . RESULTS Data from overviews of observational studies and r and omized trials suggest that a 2-mm Hg reduction in DBP would result in a 17 % decrease in the prevalence of hypertension as well as a 6 % reduction in the risk of CHD and a 15 % reduction in risk of stroke and TIAs . From an application of these results to US white men and women aged 35 to 64 years , it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher . It could prevent 84 % of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher . For stroke ( including TIAs ) , a population -wide 2-mm Hg reduction could prevent 93 % of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69 % of events for treatment for those with a DBP of 90 mm Hg or higher . A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone . Adding a population -based intervention to existing levels of hypertension treatment could prevent an estimated additional 67,000 CHD events ( 6 % ) and 34,000 stroke and TIA events ( 13 % ) annually among all those aged 35 to 64 years in the United States . CONCLUSIONS A small reduction of 2 mm Hg in DBP in the mean of the population distribution , in addition to medical treatment , could have a great public health impact on the number of CHD and stroke events prevented . Whether such DBP reductions can be achieved in the population through lifestyle interventions , in particular through sodium reduction , depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry , government agencies , and health education professionals A r and omised trial of the effects of 15 gm per day of a fish oil supplement ( MaxEPA ) on blood lipids , haemostatic variables ( including platelet function ) and albuminuria was undertaken in 41 insulin dependent diabetics . Compared with the control group there was a significant reduction in thromboxane production by platelets stimulated by collagen in vitro in the group who took the fish oil supplement . The extent of platelet aggregation was not altered but the lag phase before aggregation was prolonged . There were also statistically significant increases in plasma LDL cholesterol , fibrinogen and clotting factor X in the group who took the fish oil supplement . No other significant differences were noted Lipid peroxidation may be important in the development of cardiovascular disease , a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus ( NIDDM ) . We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde , as thiobarbituric acid reacting substances ( TBARS ) , in 23 non-insulin diabetic patients .  Plasma levels of st and ardised alpha-tocopherol ( vitamin E ) , lipid content of whole plasma and lipoprotein fractions , glycosylated haemoglobin , glycosylated low density lipoprotein ( LDL ) and fasting blood glucose were also measured . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double blind crossover fashion for 6 weeks followed by a 6 week washout period and a final 6 week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the of the active treatment periods at 6 and 18 weeks . Treatment with olive oil did not change levels of TBARS , vitamin E or indices of glycaemic control compared with baseline . Total cholesterol and triglyceride ( TG ) content of plasma and lipoprotein fractions were not significantly altered . Treatment with fish oil result ed in elevation of TBARS ( P < 0.001 ) and reduction of vitamin E ( P < 0.01 ) compared with baseline and olive oil treatment . Plasma cholesterol was unchanged . A reduction in plasma TG compared with baseline occurred but failed to reach significance ( P = 0.07 ) . Changes in apo B containing lipoproteins induced by fish oil failed to reach significance . No significant changes were observed in concentration or composition of high density lipoprotein ( HDL ) .  Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance ( P = 0.06 ) . Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil . This potentially adverse reaction may limit the therapeutic use of fish oils in such patients Some epidemiological observations indicate that 1 to 2 weekly servings of fish prevent ischemic heart disease ( IHD ) . This might be explained by an effect of the very-long-chain n-3 polyunsaturated fatty acids ( n-3 VLCPUFA ) of fish oil on lipid metabolism and /or the hemostatic system , both involved in IHD development . We studied the effect of incorporating natural fish oil ( 4 g daily equivalent to 0.91 g n-3 VLCPUFA and corresponding to one to two weekly servings of fatty fish ) into the diet in a 4-week parallel , r and omized , and double-blind trial of 47 healthy males aged 29 to 60 years .  Sunflower oil was used as placebo . The fish oil had no significant effect on plasma lipids , apolipoproteins , lipoprotein(a ) , blood coagulation FVII , fibrinogen , endogenous fibrinolysis , beta-thromboglobulin , von Willebr and factor , glucose , or insulin in fasting blood sample s. In nonfasting sample s ( n = 19 ) , fish oil was associated with an approximately 30 % decline in plasma triglycerides ( P < .02 ) and a 9 % decline in FVII protein ( P < .05 ) , whereas FVII coagulant activity and fibrinolysis were unaffected . In conclusion , our findings indicate that lowering of postpr and ial triglycerides is the only n-3 VLCPUFA effect that could contribute to primary prevention of IHD in healthy middle-aged men as assessed by currently measurable lipid and hemostatic risk markers Abstract . The effects of dietary supplementation with n‐3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non‐insulin‐dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n‐3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double‐blind cross‐over study during two consecutive 8‐week periods . The serum triglyceride ( TG ) concentrations decreased by 27 % ( P < 0.01 ) after addition of MaxEPA with a reduction of VLDL TG by 36 % ( P < 0.05 ) while LDL cholesterol increased by 6 % ( P= 0.05 ) . The fasting blood sugar and HbA1c . concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period . The highest glucose concentrations at fasting and after an i.v . glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged . The peripheral insulin sensitivity , as measured by a euglycaemic , hyperinsulinaemic clamp technique , did not change during the study . The mean plasminogen inhibitor‐1 ( PAI‐1 ) activity of the patients was elevated compared with healthy controls . In spite of the reduction of the triglyceride concentrations and unchanged insulin levels , there was a significant increase of the activity of PAI‐1 ( + 21 % , P < 0.01 ) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity . In many situations there seems to be a reduction of PAI‐1 when the triglycerides are lowered . In the diabetic patients given n‐3 fatty acids this was not the case Incidence rates and risk factors for type 2 diabetes in low-risk population s are not well documented . We investigated these in white individuals who were aged 40 - 79 years and from the population of Bruneck , Italy . Of an age- and sex-stratified r and om sample of 1,000 individuals who were identified in 1990 , 919 underwent an oral glucose tolerance test ( OGTT ) and an assessment of physiological risk factors for diabetes , including insulin resistance ( homeostasis model assessment , HOMA-IR ) , and  postchallenge insulin response  ( Sluiter 's Index ) . Diabetes at baseline by fasting or 2-h OGTT plasma glucose ( World Health Organization criteria , n = 82 ) was excluded , leaving 837 individuals who were followed for 10 years .  Incident cases of diabetes were ascertained by confirmed diabetes treatment or a fasting glucose > or=7.0 mmol/l . At follow-up , 64 individuals had developed diabetes , corresponding to a population -st and ardized incidence rate of 7.6 per 1,000 person-years . Sex- and age-adjusted incidence rates were elevated 11-fold in individuals with impaired fasting glucose at baseline , 4-fold in those with impaired glucose tolerance , 3-fold in overweight individuals , 10-fold in obese individuals , and approximately 2-fold in individuals with dyslipidemia or hypertension . Incidence rates increased with increasing HOMA-IR and decreasing Sluiter 's Index . As compared with normal insulin sensitivity and normal insulin response , individuals with low insulin sensitivity and low insulin response had a sevenfold higher risk of diabetes . Baseline impaired fasting glucose , BMI , HOMA-IR , and Sluiter 's Index were the only independent predictors of incident diabetes in multivariate analyses . We conclude that approximately 1 % of European white individuals aged 40 - 79 years develop type 2 diabetes annually and that " subdiabetic " hyperglycemia , obesity , insulin resistance , and impaired insulin response to glucose are independent predictors of diabetes Numerous investigations have demonstrated the role of thrombus formation in the pathogenesis of coronary heart disease ( CHD ) . A tendency to thrombosis may also be indicated by elevated levels of coagulation factor VII clotting activity ( FVIIc ) . Significant associations of FVIIc with increased coronary risk , however , have been found only in the Northwick Park Heart Study . Here we present the results of the 8-year follow-up of FVIIc measurements in 2780 healthy men of the Prospect i ve Cardiovascular Münster study . In the study population ( age at entry , 49.3 + /- 6.1 years , mean + /- SD ) , 130 CHD events occurred during follow-up . FVIIc was significantly higher in subjects with coronary events than in those without ( 112.4 + /- 20.1 % vs 108.7 + /- 21.4 % , P = .023 ) . Compared with individuals without coronary events , FVIIc was not significantly higher in men with nonfatal events ( 111.7 + /- 20.4 % ; P = .196 , n = 93 ) , but there was a tendency toward higher FVIIc activity in subjects with fatal events ( 114.6 + /- 19.5 % ; P = .076 , n = 37 ) . In the multiple logistic regression analysis , we did not find FVIIc to be an independent risk factor for CHD , and the significance of FVIIc disappeared after total cholesterol , LDL-cholesterol , and triglycerides were taken into account . The increase in the number of CHD events through higher levels of FVIIc was more pronounced in the presence of additional cardiovascular risk factors : smoking ; myocardial infa rct ion events in family ; angina pectoris ; high levels of fibrinogen , total cholesterol , LDL cholesterol , and triglycerides ; and a low level of HDL cholesterol . We conclude that FVIIc is a risk factor for CHD , especially in the presence of additional risk factors , and must be taken into account when assessing cardiovascular risk in men OBJECTIVE The aim of this study was to evaluate the long-term ( 6-month ) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia . RESEARCH DESIGN AND METHODS The study has been performed according to a r and omized double-blind placebo-controlled design with a parallel group sequence . After a washout period of 4 weeks and a run-in period of 3 weeks , 16 NIDDM patients with hypertriglyceridemia ( triglyceride [ TG ] , 2.25–5.65 mmol/l ) were r and omly assigned to either fish oil ( 2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months , then 1.7 g/day for 4 more months ) ( n = 8) or placebo ( n = 8) .  Diet and hypoglycemic drugs remained unchanged throughout the whole experiment . At baseline and after 6 months , insulin sensitivity was measured by euglycemic hyperinsulinemic clamp ( insulin infused , 2.0 mIU · kg−1 body wt · min−1 ) . At the same time , blood glucose control , fasting and postpr and ial serum insulin and nonesterified fatty acid ( NEFA ) concentrations , and fasting plasma lipoprotein concentrations were evaluated . RESULTS In the group treated with ffish oil compared with the baseline , there was : 1 ) a significant reduction in both plasma TG ( 2.92 ± 0.23 vs. 3.85 ± 0.32 [ mean ± SE ] mmol/l , P < 0.001 ) and VLDL-TG ( 2.35 ± 0.24 vs. 4.25 ± 0.66 mmol/l , P < 0.01 ) , without significant changes in blood glucose control ; 2 ) a significant reduction in fasting NEFA concentrations ( 572 ± 100 vs. 825 ± 131 μmol/l , P < 0.01 ) ; and 3 ) a significant enrichment in long-chain ω-3 fatty acids of erythrocyte membrane phospholipids . In the placebo group , there were no changes in any of the variables analyzed . The insulin-mediated glucose uptake was unchanged in both groups ( fish oil , 4.04 ± 0.82 mg · kg−1 · min−1 at baseline and 3.96 ± 0.50 mg · kg−1 · min−1 at 6 months ; placebo , 3.51 ± 0.62 mg · kg−1 · min−1 at baseline and 4.09 ± 0.49 mg · kg−1 · min−1 at 6 months ) . CONCLUSIONS In NIDDM patients with hypertriglyceridemia , moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides , VLDL triglycerides , and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain ω-3 fatty acids , without deteriorating blood glucose control . However , this amount of ω-3 fatty acids was unable to improve insulin sensitivity in this group of patients BACKGROUND A state of increased oxidative stress has been recognised in type 2 diabetes mellitus ( DM ) . The present study was done to assess the effects of low dose omega-3 fatty acids substitution in patients with type 2 DM with special reference to oxidative stress . METHOD Sixty-five patients with type 2 DM of body mass index ( BMI ) < 27 kg/m2 and thirty age and sex matched healthy controls were evaluated for blood glucose , blood pressure and lipid profile and oxidative stress was assessed in them by measuring lipid peroxides ( LP ) , diene conjugates ( DC ) and reduced glutathione ( RG ) in the serum .  Of the 65 , 40 motivated patients were r and omly divided into two groups -- group 1 comprising of fifteen patients prescribed a diabetic diet along with a placebo and group 2 consisting of twenty-five patients on the same diet with the addition of 0.6 g omega-3 fatty acids as one capsule Maxigard ( containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid ) twice daily . All parameters were reassessed after six weeks . RESULTS The levels of lipid peroxides ( micromol/L ) , diene conjugates ( OD units ) and reduced glutathione ( mmol GSH/L ) were significantly altered indicating increased oxidative stress in the diabetics compared to the healthy controls : 4.106 + /- 0.889 , 2.751 + /- 0.424 , 1.344 + /- 0.316 and 1.91 + /- 0.541 , 1.735 + /- 0.315 , 1.919 + /- 0.310 , respectively ( p < 0.001 for all the three ) . Patients in group 1 and 2 were comparable in all respects including oxidative stress at the start of therapy . After six weeks , on comparing the mean % changes in the three parameters of oxidative stress between the two groups , it was seen that the % change was significantly higher in group 2 ( Maxigard group ) compared to group 1 ( Placebo ; 5.22 + /- 1.056 ( p = 0.05 ) , 3.28 + /- 0.608 ( p = 0.01 ) , 5.27 + /- 0.585 ( p < 0.001 ) and 0.82 + /- 0.123 , 0.18 + /- 0.017 , 0.56 + /- 0.035 ( p < 0.001 ) , respectively . The patients in group 2 also exhibited significantly greater improvement in glycemic status , blood pressure and lipid profiles . CONCLUSIONS The present study documented the existence of a state of increased oxidative stress in type 2 diabetics . Significant beneficial effects of low dose omega-3 fatty acids substitution for PUFA-6 were observed not only on oxidative stress parameters but also on blood pressure and metabolic profile 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
Aim /hypothesisTo determine whether marine-derived n-3 polyunsaturated fatty acids ( n-3 PUFA ) ( also known as omega-3 fatty acids ) have beneficial effects on haematological and thrombogenic risk markers in addition to dyslipidaemia , in patients with type 2 diabetes .