title: Intake of a Diet High in Trans Monounsaturated Fatty Acids or Saturated Fatty Acids: Effects on postprandial insulinemia and glycemia in obese patients with NIDDM Effect of different forms of dietary hydrogenated fats on LDL particle size. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. A high-trans fatty acid diet and insulin sensitivity in young healthy women. Hydrogenation alternatives: effects of trans fatty acids and stearic acid versus linoleic acid on serum lipids and lipoproteins in humans. Dietary patterns and diabetes incidence in the Melbourne Collaborative Cohort Study. Stearic acid-rich interesterified fat and trans-rich fat raise the LDL/HDL ratio and plasma glucose relative to palm olein in humans Dietary fat and incidence of type 2 diabetes in older Iowa women. Dietary fat and meat intake in relation to risk of type 2 diabetes in men. Effect of trans-fatty acid intake on insulin sensitivity and intramuscular lipids--a randomized trial in overweight postmenopausal women. Influence of hydrogenated fat and butter on CVD risk factors: remnant-like particles, glucose and insulin, blood pressure and C-reactive protein. Effects of diets enriched in saturated (palmitic), monounsaturated (oleic), or trans (elaidic) fatty acids on insulin sensitivity and substrate oxidation in healthy adults. Publication bias in clinical research Dairy and industrial sources of trans fat do not impair peripheral insulin sensitivity in overweight women.
abstract: OBJECTIVE High intake of trans fatty acids and saturated fatty acids ( SFAs ) is known to increase the risk of coronary heart disease . We studied the effects of diets enriched in various fatty acids on postpr and ial insulinemia and fasting serum levels of lipids and lipoproteins in obese patients with NIDDM . RESEARCH DESIGN AND METHODS Sixteen obese NIDDM patients were studied in a free-living outpatient regimen . After a run-in period , the patients received three different isocaloric diets for 6 weeks using a r and omized crossover design . The patients were instructed to keep the energy intake from carbohydrate and protein constant at 50 and 20 E% ( percent of energy intake ) , respectively , on all three diets . The fat composition of the diets differed : saturated fat ( SAT ) diet ( 20 E% SFAs , 5 E% polyunsaturated fatty acids [ PUFAs ] , and 5 E% monounsaturated fatty acids [ MUFAs ] ) versus cis monounsaturated fatty acid ( CMUFA ) diet ( 20 E% cis-MUFAs , 5 E% PUFAs , and 5 E% SFAs ) versus trans monounsaturated fatty acid ( TMUFA ) diet ( 20 E% trans-MUFAs , 5 E% PUFAs , and 5 E% SFAs ) . Fasting serum levels of lipids and lipoproteins were measured at baseline and in the fasting state before meal tolerance tests at the end of each study period . Insulin secretion was assessed from incremental serum insulin and C-peptide responses during the meal tests . RESULTS BMI , waist-to-hip ratio , and glycemic control remained stable throughout the study . After meal stimulation , postpr and ial glycemic responses were similar on all diets ; however , serum insulin and C-peptide responses were greater following the TMUFA and SAT diets than following the baseline or CMUFA diets ( P < 0.05 ) . No statistical difference was found in fasting levels of serum lipids ( total cholesterol , triglyceride , phospholipid , and nonesterified fatty acids ) or lipoproteins of HDL cholesterol , VLDL cholesterol , LDL cholesterol , and apolipoprotein B between diets . CONCLUSIONS In the presence of unchanged glycemia , both dietary trans fatty acids and SFAs induce an increase in postpr and ial insulinemia in obese patients with NIDDM BACKGROUND Dietary trans fatty acids ( FAs ) , which are formed during the process of hydrogenating vegetable oil , are known to increase plasma LDL-cholesterol concentrations . However , their effect on LDL particle size has yet to be investigated . OBJECTIVE We investigated the effect of trans FA consumption on the electrophoretic characteristics of LDL particles . DESIGN Eighteen women and 18 men each consumed 5 experimental diets in r and om order for 35-d periods . Fat represented 30 % of total energy intake in each diet , with two-thirds of the fat in the form of semiliquid margarine ( 0.6 g trans FAs/100 g fat ) , soft margarine ( 9.4 g trans FAs/100 g fat ) , shortening ( 13.6 g trans FAs/100 g fat ) , stick margarine ( 26.1 g trans FAs/100 g fat ) , or butter , which was low in trans FAs ( 2.6 g trans FAs/100 g fat ) but rich in saturated fat . LDL particle size and distribution were characterized by nondenaturing , 2 - 16 % polyacrylamide gradient gel electrophoresis . RESULTS Relative to the LDL particle size observed after consumption of the butter-enriched diet , LDL particle size decreased significantly and in a dose-dependent fashion with increasing amounts of dietary trans FAs ( P < 0.001 ) . Cholesterol concentrations in large ( > 260 A ) and medium-sized ( 255 - 260 A ) LDL particles also increased proportionately to the amount of trans FAs in the diet . CONCLUSION Consumption of dietary trans FAs is associated with a deleterious increase in small , dense LDL , which further reinforces the importance of promoting diets low in trans FAs to favorably affect the lipoprotein profile BACKGROUND The effect of individual dietary fatty acids on emerging risk factors for cardiovascular disease that are associated with sub clinical inflammation is unknown . OBJECTIVE The goal was to evaluate the role of dietary fat and specific fatty acids , especially trans fatty acids , in altering concentrations of markers of inflammation in humans fed controlled diets . DESIGN In a r and omized crossover design , 50 men consumed controlled diets for 5 wk that provided 15 % of energy from protein , 39 % of energy from fat , and 46 % of energy from carbohydrate . Eight percent of fat or fatty acids was replaced across diets with the following : cholesterol , oleic acid , trans fatty acids ( TFAs ) , stearic acid ( STE ) , TFA+STE ( 4 % of energy each ) , and 12:0 - 16:0 saturated fatty acids ( LMP ) . RESULTS Fibrinogen concentrations were higher after consumption of the diet enriched in stearic acid than after consumption of the carbohydrate diet . C-reactive protein concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet , but were not significantly different after consumption of the TFA and TFA+STE diets than after consumption of the LMP diet .  Interleukin 6 concentrations were lower after consumption of the oleic acid diet than after consumption of the LMP , TFA , and STE diets .  E-selectin concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet . Consumption of the TFA but not the TFA+STE diet result ed in higher E-selectin concentrations than did the LMP diet . CONCLUSIONS These data provide evidence that dietary fatty acids can modulate markers of inflammation . Although stearic acid minimally affects LDL cholesterol , it does appear to increase fibrinogen concentrations Epidemiological and experimental studies suggest that a diet rich in saturated fat affects insulin sensitivity . Monoenes and dienes that have an usaturated bond with the trans configuration ( trans fatty acids ) resemble saturated fatty acids with respect to structure , but no published data are available on the effect of trans fatty acids on insulin sensitivity . Therefore , the effects of diets high in trans fatty acids ( TFA diet ) and oleic acid ( monounsaturated fat [ MUFA ] diet ) on glucose and lipid metabolism were studied in 14 healthy women . Subjects consumed both experimental diets for 4 weeks according to a r and omized crossover study design . Both experimental diet periods were preceded by consumption of a st and ardized baseline diet for 2 weeks . The diets provided 36.6 % to 37.9 % of energy ( E% ) as fat . In the TFA diet , there was 5.1 E% trans fatty acids , and in the MUFA diet , 5.2 E% oleic acid , substituted for saturated fatty acids in the baseline diet . A frequently sample d intravenous glucose tolerance test ( FSIGT ) was performed at the end of the experimental diet periods . Glucose effectiveness ( S(G ) ) and the insulin sensitivity index ( S(I ) ) did not differ after the two experimental diet periods . There was also no difference in the acute insulin response between the diets . The total cholesterol to high-density lipoprotein ( HDL ) cholesterol ratio and serum total triglyceride , HDL , and low-density lipoprotein ( LDL ) triglyceride and apolipoprotein B ( apoB ) concentrations were higher ( P < .05 ) after the TFA diet . In conclusion , in young healthy women , the TFA diet result ed in a higher total/HDL cholesterol ratio and an elevation in triglyceride and apo B concentrations but had no effect on glucose and insulin metabolism compared with the MUFA diet The objective of this study was to compare the effects of linoleic acid ( cis , cis-C18:2(n-6 ) ) and its hydrogenation products elaidic ( trans-C18:1(n-9 ) ) and stearic acid ( C18:0 ) on serum lipoprotein levels in humans . Twenty-six men and 30 women , all normolipemic and apparently healthy , completed the trial . Three experimental diets were supplied to every subject for 3 weeks each , in r and om order ( multiple cross-over ) . The Linoleate-diet provided 12.0 % of total energy intake as linoleic acid , 2.8 % as stearic acid , and 0.1 % as trans fatty acids . The Stearate-diet supplied 3.9 energy % as linoleic acid , 11.8 % stearic acid , and 0.3 % trans fatty acids . The Trans-diet provided 3.8 energy % as linoleic acid , 3.0 % stearic acid , and 7.7 % as monounsaturated trans fatty acids , largely elaidic acid ( trans-C18:1(n-9 ) ) . Other nutrients were constant . Fasting blood was sample d at the end of each dietary period . Mean ( + /- SD ) serum LDL cholesterol was 109 + /- 24 mg/dl ( 2.83 + /- 0.63 mmol/l ) on the Linoleate-diet . It rose to 116 + /- 27 mg/dl ( 3.00 + /- 0.71 mmol/l ) on the Stearate-diet ( change , 7 mg/dl or 0.17 mmol/l , P = 0.0008 ) and to 119 + /- 25 mg/dl ( 3.07 + /- 0.65 mmol/l ) on the Trans-diet ( change , 9 mg/dl or 0.24 mmol/l , P less than 0.0001 ) . High density lipoprotein ( HDL ) cholesterol decreased by 2 mg/dl ( 0.06 mmol/l , P less than 0.0001 ) on the Stearate-diet and by 4 mg/dl ( 0.10 mmol/l , P less than 0.0001 ) on the Trans-diet , both relative to linoleic acid . Our findings show that 7.7 % of energy ( mean , 24 g/day ) of trans fatty acids in the diet significantly lowered HDL cholesterol and raised LDL cholesterol relative to linoleic acid . Combination with earlier results ( Mensink , R. P. , and M. B. Katan . 1990 . N. Engl . J. Med . 323 : 439 - 445 ) suggests a linear dose-response relation . Replacement of linoleic acid by stearic acid also caused somewhat lower HDL cholesterol and higher LDL cholesterol levels . Hydrogenation of linoleic acid to either stearic or trans fatty acids produces fatty acids that may increase LDL and decrease HDL cholesterol relative to linoleic acid itself The authors investigated the association of dietary patterns and  type 2 diabetes  in a 4-year prospect i ve study of 36,787 adults in the Melbourne Collaborative Cohort Study ( 1990 - 1994 ) . A total of 31,641 ( 86 % ) participants completed follow-up , and 365 cases were identified . Four factors with eigenvalues of greater than 2 were identified using the principal factor method with 124 foods/beverages , followed by orthogonal rotation . Variables with factor loadings having absolute values of 0.3 or greater were used in interpreting the factors . Odds ratios for diabetes incidence across quintiles of factor scores were computed by use of logistic regression , adjusting for age , energy intake , family history of diabetes , country of birth , and other factor scores . Factor 1 , characterized by olive oil , salad vegetables , and legumes and by avoidance of sweet bakery items , margarine , and tea , was associated with country of birth but not with diabetes . Factor 2 , characterized by salad and cooked vegetables , was inversely associated with diabetes . Factor 3 , characterized by meats and fatty foods , was associated with increased diabetes risk . A range of fruits loaded strongly on factor 4 , which showed little association with diabetes . Avoidance of a dietary pattern including meats and fatty foods , as well as adherence to a pattern including salad and cooked vegetables , is recommended Background Dietary trans-rich and interesterified fats were compared to an unmodified saturated fat for their relative impact on blood lipids and plasma glucose . Each fat had melting characteristics , plasticity and solids fat content suitable for use as hardstock in margarine and other solid fat formulations . Methods Thirty human volunteers were fed complete , whole food diets during 4 wk periods , where total fat ( ~31 % daily energy , > 70 % from the test fats ) and fatty acid composition were tightly controlled . A crossover design was used with 3 r and omly-assigned diet rotations and repeated- measures analysis . One test fat rotation was based on palm olein ( POL ) and provided 12.0 percent of energy ( % en ) as palmitic acid ( 16:0 ) ; a second contained trans-rich partially hydrogenated soybean oil ( PHSO ) and provided 3.2 % en as trans fatty acids plus 6.5 % en as 16:0 , while the third used an interesterified fat ( IE ) and provided 12.5 % en as stearic acid ( 18:0 ) . After 4 wk the plasma lipoproteins , fatty acid profile , as well as fasting glucose and insulin were assessed . In addition , after 2 wk into each period an 8 h postpr and ial challenge was initiated in a subset of 19 subjects who consumed a meal containing 53 g of test fat . Results After 4 wk , both PHSO and IE fats significantly elevated both the LDL/HDL ratio and fasting blood glucose , the latter almost 20 % in the IE group relative to POL . Fasting 4 wk insulin was 10 % lower after PHSO ( p > 0.05 ) and 22 % lower after IE ( p < 0.001 ) compared to POL . For the postpr and ial study the glucose incremental area under the curve ( IAUC ) following the IE meal was 40 % greater than after either other meal ( p < 0.001 ) , and was linked to relatively depressed insulin and C-peptide ( p < 0.05 ) . Conclusion Both PHSO and IE fats altered the metabolism of lipoproteins and glucose relative to an unmodified saturated fat when fed to humans under identical circumstances OBJECTIVE To examine the associations between reported intakes of dietary fat and incident type 2 diabetes .  RESEARCH DESIGN AND METHODS We studied the relation between dietary fatty acids and diabetes in a prospect i ve cohort study of 35,988 older women who initially did not have diabetes .  Diet was assessed with a  food frequency question  naire at baseline , and 1,890 incident cases of diabetes occurred during 11 years of follow-up . RESULTS After adjusting for age , smoking , alcohol consumption , BMI , waist-to-hip ratio , physical activity , demographic factors , and dietary magnesium and cereal fiber , diabetes incidence was negatively associated with dietary polyunsaturated fatty acids , vegetable fat , and trans fatty acids and positively associated with omega-3 fatty acids , cholesterol , and the Keys score . After simultaneous adjustment for other dietary fat , only vegetable fat remained clearly related to diabetes risk . Relative risks across quintiles of vegetable fat intake were 1.00 , 0.90 , 0.87 , 0.84 , and 0.82 ( P = 0.02 ) . Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score . CONCLUSIONS These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol OBJECTIVE To examine dietary fat and meat intake in relation to risk of type 2 diabetes .  RESEARCH DESIGN AND METHODS We prospect ively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40 - 75 years and free of diagnosed diabetes , cardiovascular disease , and cancer in 1986 .  Diet was assessed by a vali date d food frequency question naire and up date d in 1990 and 1994 . During 12 years of follow-up , we ascertained 1,321 incident cases of type 2 diabetes . RESULTS Intakes of  total fat  ( multivariate RR for extreme quintiles 1.27 , CI 1.04 - 1.55 , P for trend=0.02 ) and saturated fat ( 1.34 , 1.09 - 1.66 , P for trend=0.01 ) were associated with a higher risk of type 2 diabetes . However , these associations disappeared after additional adjustment for BMI ( total fat RR 0.97 , CI 0.79 - 1.18 ; saturated fat 0.97 , 0.79 - 1.20 ) . Intakes of oleic acid , trans-fat , long-chain n-3 fat , and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment . Linoleic acid was associated with a lower risk of type 2 diabetes in men < 65 years of age ( RR 0.74 , CI 0.60 - 0.92 , P for trend=0.01 ) and in men with a BMI < 25 kg/m(2 ) ( 0.53 , 0.33 - 0.85 , P for trend=0.006 ) but not in older and obese men . Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes ( RR 1.46 , CI 1.14 - 1.86 for > or = 5/week vs. < 1/month , P for trend < 0.0001 ) . CONCLUSIONS Total and saturated fat intake were associated with a higher risk of type 2 diabetes , but these associations were not independent of BMI . Frequent consumption of processed meats may increase risk of type 2 diabetes Intake of industrially produced trans-fatty acids ( TFA ) has been linked to increased risk of type 2 diabetes mellitus in observational studies . We investigated the causality of this association by examining if a high intake of TFA impairs measures of glucose homeostasis and induces intramuscular lipid deposition in abdominally obese women . In a double-blind , parallel dietary intervention study , 52 healthy but overweight postmenopausal women were r and omized to receive either partially hydrogenated soybean oil ( 15 g/d TFA ) or a control oil ( mainly oleic and palmitic acid ) for 16 weeks . Three markers of glucose homeostasis and 4 markers of lipolysis were derived from glucose , insulin , C-peptide , nonesterified fatty acid , and glycerol concentrations during a 3-hour frequent sampling oral glucose tolerance test . Intramuscular lipids were assessed by magnetic resonance spectroscopy . Forty-nine women completed the  study .  Insulin sensitivity ( assessed by ISI(composite ) ) , β-cell function ( the disposition index ) , and the metabolic clearance rate of insulin were not significantly affected by the dietary intervention . Neither was the ability of insulin to suppress plasma nonesterified fatty acid and glycerol during oral glucose ingestion nor the intramuscular lipid deposition . In conclusion , high TFA intake did not affect glucose metabolism over 16 weeks in postmenopausal overweight women . A study population with a stronger predisposition to insulin resistance and /or a longer duration of exposure may be required for insulin sensitivity to be affected by intake of industrial TFA Dietary trans fatty acids/partially-hydrogenated fat has been associated with increased risk of developing cardiovascular disease ( CVD ) , possibly greater than predicted from changes in lipoprotein levels . To explore this issue further potential risk factors were assessed in subjects provided with each of six diets in r and omized order containing as the major source of fat : soybean oil , semi-liquid margarine , soft margarine , shortening , traditional stick margarine or butter .  Plasma fatty acid profiles reflected diet , with triglyceride and phospholipid subfractions affected to a greater extent than cholesteryl ester . Non-fasting LDL-cholesterol levels were 144+/-27 , 141+/-27 , 146+/-26 , 148+/-30 , 151+/-29 and 165+/-31 mg/dl ( P<0.001 ) and total cholesterol/HDL-cholesterol ratios were 5.50+/-1.25 , 5.54+/-1.50 , 5.69+/-1.29 , 5.82+/-1.40 , 6.11+/-1.30 and 5.94+/-1.43 ( P=0.011 ) , respectively , whereas other lipoprotein levels were not significantly different . Remnant-like particles levels were unaffected by dietary fat , either in the fasting or non-fasting state . Differences in fasting insulin and glucose levels were small and would not be predicted to have a large impact on glucose homeostasis . There was no significant effect of dietary fat type on C-reactive protein levels or blood pressure . These data suggest that , as previously demonstrated , the major CVD risk factor adversely affected by dietary trans fatty acids/partially-hydrogenated fat is LDL-cholesterol levels and total cholesterol/HDL-cholesterol ratios OBJECTIVE Diets high in total and saturated fat are associated with insulin resistance . This study examined the effects of feeding monounsaturated , saturated , and trans fatty acids on insulin action in healthy adults . RESEARCH DESIGN AND METHODS A r and omized , double-blind , crossover study was conducted comparing three controlled 4-week diets ( 57 % carbohydrate , 28 % fat , and 15 % protein ) enriched with different fatty acids in 25 healthy men and women . The monounsaturated fat diet ( M ) had 9 % of energy as C18:1cis ( oleic acid ) . The saturated fat diet ( S ) had 9 % of energy as palmitic acid , and the trans fatty acid diet ( T ) had 9 % as C18:1trans . Body weight was kept constant throughout the study . After each diet period , insulin pulsatile secretion , insulin sensitivity index ( S(I ) ) by the minimal model method , serum lipids , and fat oxidation by indirect calorimetry were measured . RESULTS Mean S(I ) for the M , S , and T diets was 3.44 + /- 0.26 , 3.20 + /- 0.26 , and 3.40 + /- 0.26 x 10(-4 ) min(-1 ) . microU(-1 ) . ml(-1 ) , respectively ( NS ) . S(I ) decreased by 24 % on the S versus M diet in overweight subjects but was unchanged in lean subjects ( NS ) . Insulin secretion was unaffected by diet , whereas total and HDL cholesterol increased significantly on the S diet . Subjects oxidized the least fat on the M diet ( 26.0 + /- 1.5 g/day ) and the most fat on the T diet ( 31.4 + /- 1.5 g/day ) ( P = 0.02 ) . CONCLUSIONS Dietary fatty acid composition significantly influenced fat oxidation but did not impact insulin sensitivity or secretion in lean individuals . Overweight individuals were more susceptible to developing insulin resistance on high-saturated fat diets In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies BACKGROUND The 2 major dietary sources of trans fatty acids ( TFAs ) are partially hydrogenated oils and ruminant-derived products . Epidemiologic data suggest that chronic consumption of industrial sources of TFAs could be damaging to insulin sensitivity , but intervention studies on this issue have remained inconclusive . OBJECTIVE The trial was design ed to compare the effects of dairy compared with industrial sources of TFAs on insulin sensitivity in overweight women . DESIGN Sixty-three healthy women with abdominal obesity [ waist circumference > 88 cm and a body mass index ( in kg/m(2 ) ) > 28 ] were recruited . After a run-in period , the volunteers were r and omly assigned to consume 1 of 3 four-week diets : 60 g low-TFA lipids/d ( 0.54 g/d ; n = 21 ) , ruminant TFA-rich lipids ( 4.86 g/d ; n = 21 ) , or industrial TFA-rich lipids ( 5.58 g/d ; n = 21 ) . Changes in peripheral insulin sensitivity were assessed by using hyperinsulinemic-euglycemic clamps . RESULTS After the intervention period , fasting glycemia and insulinemia and insulin sensitivity were not significantly modified in either group ( P > 0.05 ) . CONCLUSIONS These data indicate that consumption of dairy- and industrial- source TFAs for 4 wk at nutritional levels do not impair peripheral insulin sensitivity in insulin-resistant women . Our study may not preassess the effects of TFAs in normal insulin-sensitive individuals . This trial was registered at Clinical Trials.gov as NCT00617435
target: RESULTS Increased TFA intake did not result in significant changes in glucose or insulin concentrations .
  Our analysis also showed the absence of publication bias and any dose-response relations between the ES and TFA intake .
  Increased TFA intake does not result in changes in glucose , insulin , or triglyceride concentrations but leads to an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol concentrations .
  There is no evidence to support a potential benefit of the reduction of dietary TFA intake on glucose homeostasis
background: BACKGROUND Although evidence from cohort studies has suggested that trans fatty acid ( TFA ) consumption may be associated with insulin resistance and diabetes , r and omized placebo-controlled trials ( RCTs ) have yielded conflicting results .
  OBJECTIVE In a meta- analysis , we combined all available RCTs that examined the role of  TFA intake  on  glucose homeostasis .