Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians. A Comparison of the Effects of n-3 Fatty Acids From Linseed Oil and Fish Oil in Well-Controlled Type II Diabetes A Randomized Double-Blinded, Placebo-Controlled Trial Investigating the Effect of Fish Oil Supplementation on Gene Expression Related to Insulin Action, Blood Lipids, and Inflammation in Gestational Diabetes Mellitus-Fish Oil Supplementation and Gestational Diabetes Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial. [The effect of fish oil on the secretion and effect of insulin in patients with type II diabetes]. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids? Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. [Effect of fish oil concentrate on the lipoprotein profile of patients with type II diabetes mellitus]. Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. Dietary supplementation with n-3 fatty acids increases gluconeogenesis from glycerol but not hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. Dietary fish oil augments nitric oxide production or release in patients with Type 2 (non-insulin-dependent) diabetes mellitus Treatment for 6 months with fish oil-derived n-3 polyunsaturated fatty acids has neutral effects on glycemic control but improves dyslipidemia in type 2 diabetic patients with abdominal obesity: a randomized, double-blind, placebo-controlled trial
BACKGROUND Indian Asians in Western countries have a higher rate of coronary artery disease than do the indigenous white population s , and this higher rate may be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids ( PUFAs ) . OBJECTIVE The objective of the study was to test the hypothesis that a high background dietary intake of n-6 PUFA attenuates the effects of fish-oil supplementation on insulin sensitivity and associated blood lipids of the metabolic syndrome . DESIGN Twenty-nine Indian Asian men were recruited to participate in a 12-wk dietary intervention trial . Volunteers were r and omly assigned to receive either a moderate or a high n-6 PUFA diet featuring modified oils and spreads over a 6-wk period . After this 6-wk period , both groups were supplemented with 4.0 g fish oil/d ( 2.5 g eicosapentaenoic acid + docosahexaenoic acid ) for an additional 6 wk in combination with the dietary treatment . Volunteers participated in a postpr and ial study and an insulin sensitivity test after the 6-wk dietary intervention and again after the fish-oil supplementation period . RESULTS There was no significant time x treatment interaction for blood lipids or insulin action after dietary intervention with the moderate or high n-6 PUFA diets in combination with fish oil . After the 6-wk period of fish oil supplementation , fasting and postpr and ial plasma triacylglycerol concentrations decreased significantly . CONCLUSION The background dietary n-6 PUFA concentration did not modulate the effect of fish-oil supplementation on blood lipids or measures of insulin sensitivity in this ethnic group 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 Gestational diabetes mellitus ( GDM ) is a common complication of pregnancy , and it is mostly associated with postpartum diabetes , insulin resistance , and dyslipidemia . Fish oil ( omega-3 ) supplementation has been shown to reduce the risk of different chronic diseases such as cardiovascular disease , type 2 diabetes , and cancers , though the evidence of its impact on gestational diabetes is scarce . Our goal in this study was to determine the effect of fish oil administration on gene expression related to insulin action , blood lipids , and inflammation in women with GDM . Participants with GDM ( n = 40 ) , aged 18–40 years , were r and omized to take either 1000 mg fish oil capsules , containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid ( n = 20 ) , or placebo ( n = 20 ) twice a day for 6 weeks . Gene expression related to insulin , lipids , and inflammation was quantified in peripheral blood mononuclear cells ( P BMC s ) of GDM women using Reverse Transcription Polymerase Chain Reaction ( RT-PCR ) method . Results of RT-PCR indicated that omega-3 supplementation  upregulated gene expression of peroxisome proliferator-activated receptor gamma ( PPAR-γ ) ( P = 0.04 ) in P BMC s of patients with GDM , compared with the placebo . In addition , gene expression of the low-density lipoprotein receptor ( LDLR ) ( P < 0.001 ) , interleukin-1 ( IL-1 ) ( P = 0.007 ) , and tumor necrosis factor alpha ( TNF-α ) ( P = 0.01 ) was downregulated in P BMC s of women with GDM , following omega-3 supplementation . No significant effect of omega-3 supplementation was indicated on gene expression of IL-8 in P BMC s of patients with GDM . Overall , fish oil supplementation for 6 weeks in women with GDM  significantly improved gene expression of PPAR-γ , IL-1 , and TNF-α , but not gene expression of IL-8 The effects of fish oil ( FO ) supplementation on glycaemic control are unclear , and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14 % as n-3 PUFA . Subjects ( n 36 , thirty-three completed ) were paired based on metabolic parameters and allocated into a parallel double-blind r and omised trial with one of each pair offered daily either 6 g of FO ( 3·9 g n-3 PUFA ) or 6 g of maize oil ( MO ) for 9 months . Hyperinsulinaemic-euglycaemic-euaminoacidaemic ( HIEGEAA ) clamps ( with [ 6,6 2H2 glucose ] ) were performed at the start and end of the intervention . Endogenous glucose production ( EGP ) and whole-body protein turnover ( WBPT ) were each measured after an overnight fast . The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control . The secondary outcome involved the effect of oil type on WBPT . Subjects on  FO ( n 16 ) had increased erythrocyte n-3 PUFA concentrations > 14 % , whereas subjects on MO ( n 17 ) had unaltered n-3 PUFA concentrations at 9 % . Type of oil had no effect on fasting EGP , insulin sensitivity or total glucose disposal during the HIEGEAA clamp . In contrast , under insulin-stimulated conditions , total protein disposal ( P=0·007 ) and endogenous WBPT ( P=0·001 ) were both increased with FO . In an associated pilot study ( n 4 , three completed ) , although n-3 PUFA in erythrocyte membranes increased to > 14 % with the FO supplement , the enrichment in muscle membranes remained lower ( 8 % ; P<0·001 ) . In conclusion , long-term supplementation with FO , at amounts near the safety limits set by regulatory authorities in Europe and the USA , did not alter glycaemic control but did have an impact on WBPT 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 AIM To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity , insulin secretion , beta-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat , also in relation to their habitual dietary intake of n-6 and n-3 fatty acid .  METHODS AND RESULTS One hundred and sixty-two healthy individuals were r and omly assigned to follow either one of two isoenergetic diets for 3 months , one rich in monounsaturated fats and the other rich in saturated fats . Within each group there was a second r and omisation to fish oil ( n-3 fatty acids 3.6 g/day ) or placebo . At the beginning and at the end of the treatment periods insulin sensitivity ( SI ) , first phase insulin response ( FPIR ) and glucose tolerance ( K(G)-value ) were evaluated by the intravenous glucose tolerance test ( IVGTT ) . Fish oil did not have any effect on SI , FPIR , K(G)-value and disposition index in either diet . Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline , there was no change in SI ( Delta SI 0.42+/-0.34 on fish oil vs 0.14+/-0.23 on placebo for those with n-6/n-3 < 4.85 ; -1.03+/-0.47 on fish oil vs -0.27+/-0.32 on placebo for those with n-6/n-3 > 4.85 ) ( M+/-SE ) , FPIR ( Delta FPIR 135.9+/-78.9 vs 157.2+/-157.5 pmol/L ; 38.8+/-181.7 vs 357.1+/-181.7 pmol/L ) , K(G)-value ( Delta K(G ) 0.14+/-0.15 vs 0.12+/-0.11 ; -0.32+/-0.16 vs 0.15+/-0.15 ) or disposition index ( Delta disposition index 1465.4+/-830.4 vs 953.8+/-690.0 ; -1641.6+/-1034.3 vs 446.6+/-905.1 ) . Considering the 75th percentile of n-6/n-3 ratio ( 5.82 ) the results on insulin sensitivity , insulin secretion and disposition index were confirmed , while , in this more extreme situation , n-3 fatty acid supplementation induced a significant deterioration of K(G)-value ( p=0.02 ) . CONCLUSIONS In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity , insulin secretion , beta-cell function or glucose tolerance . The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account OBJECTIVE Offspring of patients with type 2 diabetes ( OPDs ) exhibits endothelial dysfunction ( ED ) associated with a chronic inflammatory state . N-3 polyunsaturated fatty acids ( n-3 PUFA ) may have antioxidant and anti-inflammatory properties that are beneficial for cardiovascular and metabolic health . Therefore , in the present study , we tested the hypothesis that dietary supplementation with fish oil rich in n-3 PUFA may improve ED in otherwise healthy OPDs . METHODS AND DESIGN A double-blind , placebo-controlled trial was conducted with 50 OPDs . Participants were r and omized to treatment with either placebo or n-3 PUFA ( 2g/day ) for 12 weeks . Before and after treatment we evaluated endothelial function ( using flow-mediated dilation ( FMD ) of the brachial artery ) , circulating inflammatory markers ( adiponectin , TNF-alpha , and high sensitivity-CRP ) , and insulin resistance ( QUICKI ) . RESULTS No significant changes were observed in study outcomes in subjects treated with placebo . By contrast , when compared with baseline values , subjects treated with n-3 PUFA had significant improvement in FMD ( 9.1+/-5.8 % vs. 11.7+/-4.4 % , p=0.02 ) that was accompanied by decreased plasma triglycerides ( 117+/-73mg/dl vs. 86+/-44mg/dl , p=0.001 ) and TNF-alpha levels ( 8.9+/-2.3pg/ml vs. 6.8+/-2.7pg/ml , p=0.001 ) , and a trend towards increased plasma adiponectin levels ( 7.8+/-4.5microg/ml vs. 9.5+/-5.1microg/ml , p=0.09 ) . When data were analyzed by multiple regression analysis , decreased TNF-alpha after treatment with n-3 PUFA predicted increased FMD . CONCLUSION Dietary supplementation with n-3 PUFA significantly improved endothelial function and reduced pro-inflammatory markers in OPDs . Thus , fish oil consumption may have beneficial cardiovascular and metabolic health effects in otherwise healthy subjects predisposed to diabetes and its vascular complications OBJECTIVE To determine whether dietary supplementation with fish oil adversely affects glycemic control in patients with hypertension . DESIGN R and omized , double-blind , placebo-controlled study . PATIENTS 78 persons with untreated hypertension recruited from a population survey . INTERVENTION Participants were r and omly assigned to receive eicosapentaenoic and docosahexaenoic acids , 4 g/d , or corn oil placebo , 4 g/d , for 16 weeks . MEASUREMENTS An oral glucose tolerance test ; assessment s of insulin release , glucose disposal , and insulin sensitivity done using the hyperglycemic clamp technique to keep plasma glucose levels at 10 mmol/L for 180 minutes ; assessment of insulin sensitivity done using a euglycemic hyperinsulinemic clamp technique ( infusing insulin and glucose to keep plasma glucose levels at 5 mmol/L ) ; assessment s of lipid levels and blood pressure . Measurements were done before and after intervention . RESULTS Changes in integrated glucose and insulin response after the oral glucose challenge did not differ between the fish oil and corn oil groups after intervention ( -0.6 + /- 0.7 compared with -1.0 + /- 0.6 mmol/L [ P > 0.3 ] for integrated glucose and 143 + /- 76 compared with 169 + /- 84 pmol/L [ P > 0.3 ] for insulin response ) . Changes in first-phase insulin release ( 34 + /- 72 pmol/L in the fish oil group compared with 191 + /- 112 pmol/L in the corn oil group [ P > 0.3 ] ) , second-phase insulin release ( 179 + /- 66 pmol/L compared with 257 + /- 122 pmol/L [ P > 0.3 ] ) , and insulin sensitivity index ( -0.03 + /- 0.01 compared with -0.01 + /- 0.01 [ mumol/kg.min divided by pmol/L ] ; P > 0.3 ) were also similar in both groups after treatment . Fish oil lowered systolic blood pressure by 3.8 mm Hg more than control ( P = 0.04 ) and lowered diastolic blood pressure by 2.0 mm Hg more than control ( P = 0.10 ) . After fish oil treatment , triglyceride levels decreased by 0.28 + /- 0.08 mmol/L more than control ( P = 0.01 ) , and very-low-density lipoprotein cholesterol levels decreased by 0.13 + /- 0.04 mmol/L more than control ( P = 0.01 ) . CONCLUSION Fish oil , in doses that reduce blood pressure and lipid levels in hypertensive persons , does not adversely affect glucose metabolism Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with increased very-low-density lipoprotein ( VLDL ) and triglyceride concentrations as abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil has a strong triglyceride lowering effect in case of normolipemic subjects , we investigated the influence of supplementary fish oil diet in patients suffering from NIDDM ( n = 19 ) , who until now were not treated by drugs but only by diet . The study was started with a placebo-run-in-period for four weeks ( phase I , 6 g rape seed oil capsules/d ) , followed by a verum period for twelve weeks ( phase II , 6 g fish oil concentrate capsules/d ) , and a wash-out-period for four weeks ( phase III , 6 g rape seed oil capsules/d ) . The fish oil supplementation contained at least 3 g eicosapentenoic and docosahexenoic acid . The lipoproteins , apolipoproteins , blood glucose , and insulin level ( fasting and after load test ) were checked at the beginning and at the end of each phase . In comparison to the placebo rape seed oil supplementation , the fish oil diet effected a decrease of serum triglycerides by 29 % . LDL-cholesterol increased by 9 % , HDL-cholesterol by 9 % ( especially HDL2-cholesterol ) , and apolipoprotein B by 4 % . Apolipoprotein A-I was reduced by 9 % . The fasting blood glucose and the glucose load test as the insulin level ( fasting and after load test ) showed no significant changes at the end of the verum period in comparison to the run-in-phase . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Fish-oil supplementation decreases serum triacylglycerols but may worsen hyperglycemia in patients with non-insulin-dependent diabetes mellitus . The reason for the possible deterioration of glycemia is unclear . We examined whether inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis , glycerol gluconeogenesis , or fatty acid oxidation .  Nine obese patients with non-insulin-dependent diabetes mellitus participated in a r and omized double-blind crossover study in which 6 wk of n-3 fatty acid supplementation ( 12 g fish oil ) was compared with 6 wk of corn plus olive oil .  Serum triacylglycerols decreased by 30 % during n-3 fatty acid supplementation . Glycerol gluconeogenesis ( [U-14C]glycerol ) increased by 32 % . However , overall glucose production ( [3 - 3H]glucose ) , glycemic control , and fatty acid oxidation remained unchanged . Thus , 6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with non-insulin-dependent diabetes mellitus without worsening glycemic control . However , n-3 fatty acid supplementation increases glycerol gluconeogenesis , which could contribute to deterioration of glycemic control during long-term treatment with high doses of fish-oil supplements 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 Purpose This study aim ed to determine the effects of fish oil-derived n-3 PUFA on glycemic control and lipid profiles in type 2 diabetic patients with abdominal obesity . Methods In a r and omized , double-blind , placebo-controlled trial , 100 type 2 diabetic patients with abdominal obesity were r and omized into two groups including 4 g/day of fish oil ( 2.4 g n-3 PUFA ) or placebo ( corn oil ) for 6 months . Serum fatty acid , body composition , as well as markers of glucose regulation and lipid parameters were measured before and after intervention . Results Thirty-five men and 64 women aged 65.4 ± 5.3 years completed the intervention . Although body composition was unchanged , serum EPA and DHA were higher in the fish oil group than those in the placebo group ( P < 0.001 and P < 0.001 , respectively ) . Serum triglyceride ( TG ) decreased ( P = 0.007 ) , whereas high-density lipoprotein cholesterol ( HDL-C ) increased ( P = 0.006 ) in the fish oil group compared with the placebo group after 6 months . Serum total cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , the ratio of LDL-C to HDL-C , and glycemic control ( measured by serum glucose , glycated hemoglobin , insulin , and homeostasis model assessment –insulin resistance ) were not significantly different between the two groups after 6 months . Conclusions This study showed that 6 months of fish oil supplement had no statistically significant effects on glycemic control , but improved TG and HDL-C in type 2 diabetic patients with abdominal obesity . Trial registration Chictr.org ChiCTR-TRC-14005084
Conclusions Short-term fish oil supplementation is associated with increasing the insulin sensitivity among those people with metabolic disorders
Background Fish oil supplementation has been shown to be associated with a lower risk of metabolic syndrome and benefit a wide range of chronic diseases , such as cardiovascular disease , type 2 diabetes and several types of cancers .
However , the evidence of fish oil supplementation on glucose metabolism and insulin sensitivity is still controversial .
This meta- analysis summarized the exist evidence of the relationship between fish oil supplementation and insulin sensitivity and aim ed to evaluate whether fish oil supplementation could improve insulin sensitivity .