Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion.

AIMS: Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). METHODS: Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) +/- sd, 34.8 +/- 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 +/- 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 +/- 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. RESULTS: Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). CONCLUSIONS: MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery.

OBJECTIVE: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined. DESIGN: Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal (770 kcal). SUBJECTS: Twenty men and 20 women were included: 10 middle-aged morbidly obese (body mass index (BMI) 43.9+/-3.3 kg/m(2)), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.7+/-5.8 kg/m(2)), 10 middle-aged non-obese (BMI 23.5+/-2.2 kg/m(2)) and 10 young non-obese (BMI 22.7+/-1.8 kg/m(2)). MEASUREMENTS: Ghrelin, glucose and insulin levels were analysed pre- and postprandially. RESULTS: In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both age-matched and young non-obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression. CONCLUSION: The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.

Plasma antioxidant capacity among middle-aged men: the contribution of uric acid.

OBJECTIVE: Although assays of plasma antioxidant capacity encompass interactions between various antioxidants, uric acid concentration can exert a predominant effect on results. Therefore, individual differences in uric acid concentration may explain a many of the differences in antioxidant capacity. The objective of this study was to measure the antioxidant capacity of plasma samples with and without uric acid in order to provide more information about how the concept of antioxidant capacity could be applied. MATERIAL AND METHODS: Antioxidant capacity was measured using an enhanced chemiluminescence assay, and uric acid was removed from the samples using uricase. RESULTS: Antioxidant capacity was positively correlated with uric acid concentration, body mass index, waist circumference, abdominal sagittal diameter and the concentrations of insulin and triglycerides. These correlations were not evident when uric acid was eliminated from the sample, but antioxidant capacity was correlated with lipid concentration; this may partly reflect tocopherols that are transported by lipid molecules. CONCLUSIONS: The significance of the contribution of uric acid to the antioxidant capacity could differ according to the type of study. Antioxidant capacity measurements in cross-sectional studies may be presented both with and without the contribution of uric acid, because the absence of such data complicates interpretation of results when different populations are compared.

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects.

OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA < 4 (insulin sensitive) and HOMA>9 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulin-resistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

Serum magnesium status during lipid-lowering drug treatment in non-insulin-dependent diabetic patients.

Serum magnesium concentration (S-Mg) has been reported to be inversely associated with atherogenic lipid fractions and with blood glucose concentrations. In some studies on humans, oral magnesium supplementation has been found to improve the lipoprotein balance. Against this background the present study was undertaken to determine whether reductions in atherogenic lipid fractions are associated with S-Mg alterations. Total S-Mg was measured in 23 patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with the lipid-lowering drugs gemfibrozil and simvastatin in a double-blind cross-over study. The mean S-Mg at the end of the initial placebo period, ie, before active treatment, was 0.80 (SD 0.06) mmol/L. Treatment with gemfibrozil 600 mg twice daily for 4 months decreased S-Mg by 0.02 mmol/L (P =.02), and treatment with simvastatin 10 mg daily for 4 months again decreased S-Mg by 0.02 mmol/L (P =.10; not significant [NS]) The changes in S-Mg during the 2 different treatment periods were closely correlated (r = 0.66, P <.001). Fasting plasma glucose concentrations increased significantly by 17% during both drug regimens. The changes in fasting plasma glucose and S-Mg were significantly correlated both during gemfibrozil treatment (r = -0.56, P <.01) and during treatment with simvastatin (r = -0.44, P <.05). Changes in glucose tolerance or insulin sensitivity did not correlate to changes in S-Mg. The associations between changes in serum very-low-density lipoprotein (VLDL) fractions and S-Mg did not reach statistical significance (r = -0.37, P <.10). Changes in low-density lipoprotein (LDL) cholesterol and S-Mg did not correlate. In conclusion, total S-Mg concentration decreased during treatment with gemfibrozil and simvastatin in patients with NIDDM. During both drug regimens changes in S-Mg status were inversely correlated to changes in plasma glucose concentrations, while changes in lipid status were not significantly correlated with changes in S-Mg.

Corn and sesame oils increase serum gamma-tocopherol concentrations in healthy Swedish women.

We studied the effects of dietary intervention with three vegetable oils (Linola, corn or sesame oil, all good sources of gamma-tocopherol) on absolute and relative concentrations of alpha- and gamma-tocopherol in human serum. The oils contained only small amounts of linolenic acid but varying amounts of oleic and linoleic acids, and they had different concentrations of alpha-tocopherol. Forty healthy female students (mean age 26 y) were randomly assigned to one of three groups and consumed a diet that contained one of the three oils for 4 wk. Refined oils were distributed as ingredients in specially prepared buns, in margarine or as dressing. Serum tocopherols, serum lipoproteins and plasma malondialdehyde concentrations were measured. The gamma-tocopherol concentrations normalized to serum lipids increased significantly in the corn and sesame oil groups (P < 0.01), and the alpha-/gamma-tocopherol ratios decreased significantly from baseline concentrations in all groups (P < 0.05). The alpha-tocopherol concentrations did not change during the diet period in any of the three groups. Serum cholesterol, serum apolipoprotein B and plasma malondialdehyde concentrations decreased significantly only in the Linola oil group (P < 0.05). These data show that a moderately modified natural diet that contains both alpha- and gamma-tocopherol increases the serum gamma-tocopherol concentration in healthy women without affecting the serum alpha-tocopherol concentration.

The alpha and gamma tocopherol levels in serum are influenced by the dietary fat quality.

BACKGROUND: Alpha tocopherol in serum is thought to be of importance in protecting lipids against oxidation and low serum levels of alpha tocopherol has been suggested to increase the risk for coronary heart disease. However, low levels of gamma, rather than alpha, tocopherol have been found in patients with manifest coronary heart disease and in populations with a high incidence of coronary heart disease. AIM: The aim of this study was to determine the tocopherol concentrations in serum after two diets with identical nutrient content but with different fat quality, enriched in butter and rapeseed oil-based fats, respectively. METHOD: Twenty moderately hyperlipidemic, healthy subjects (six females and 14 males) participated in this double-blind cross-over study, where two isoenergetic diets were given in a randomized order during two 3-week periods, interrupted by a wash-out period of 3-4 weeks. RESULTS: The lipid-corrected serum concentrations of alpha and gamma tocopherol increased during the diet rich in rapeseed oil (by 7 and 23%, respectively) compared with on the baseline diet (P < 0.001), while these concentrations decreased (by 5 and 37%, respectively, P < 0.01) during the diet rich in saturated fat. The ratio between alpha and gamma tocopherol decreased significantly during the rapeseed oil diet (-23%, P < 0.01) and increased (+46%, P < 0.001) during the butter diet. CONCLUSION: Alpha and gamma tocopherol levels in serum are influenced by the type of fat used in the diet. The most unexpected finding is that the lipid-adjusted gamma tocopherol concentration significantly decreased by 37% during a diet rich in saturated fat with an increased ratio between alpha and gamma tocopherol, similar to the situation found in CHD patients.

Diet, nutrition and diabetes mellitus.

Nutritional management of diabetes mellitus, and the importance of diet in the development of insulin resistance, have for many years been important areas of research and education at the Unit for Clinical Nutrition Research at the Department of Public Health and Caring Sciences (formerly Department of Geriatrics) at Uppsala University. The research has more recently focussed on effects of dietary fat quality in the development of insulin resistance and in treatment of diabetes, on interaction between dietary fat and physical activity in relation to insulin sensitivity and on the importance of carbohydrate rich foods with low glycaemic index in the diabetic diet. Much work has also been directed towards development of educational material about nutrition recommendations and dietary treatment in diabetes mellitus. The ultimate goals for all our efforts are to visualize, and promote, the possibilities and fundamental importance of lifestyle changes. This includes an improved diet and increased physical activity, in the prevention and treatment of diabetes mellitus.

Sagittal abdominal diameter compared with other anthropometric measurements in relation to cardiovascular risk.

BACKGROUND: Abdominal adiposity has been described as an independent risk factor for coronary heart disease. Sagittal abdominal diameter has been found to be closely related to the amount of visceral adipose tissue. AIM: To compare the sagittal abdominal diameter with other anthropometric measures regarding their relationships to risk factors for coronary heart disease (CHD). DESIGN: A study of 885 men and women participating in a health survey. MEASUREMENTS: Sagittal abdominal diameter, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, serum concentrations of risk factors for CHD, blood pressure. RESULTS: In men the sagittal abdominal diameter showed stronger correlations to the CHD risk factors serum cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, insulin, apolipoprotein B (apoB), plasminogen activator inhibitor tissue-type plasminogen activator (t-PA) and lipid-corrected alpha tocopherol, and to systolic and diastolic blood pressures than the other anthropometric measurements. In women, compared with the other anthropometric measurements the sagittal abdominal diameter was more strongly correlated to serum cholesterol, LDL cholesterol, LDL/HDL (high-density lipoprotein), apo B and t-PA, and to systolic and diastolic blood pressure. The sagittal abdominal diameter showed a stronger correlation to 'total risk' for cardiovascular disease (+ 0.66 for men, 0.62 for women), than waist circumference (+ 0.63 for men, + 0.57 for women) and waist-to-hip ratio (+ 0.61 for men and +0.48 for women; P <0.0001 for all correlations). This diameter was also more strongly correlated to 'metabolic risk' (+ 0.64 for men, + 0.59 for women) than waist circumference (+ 0.60 for men, + 0.59 for women) and waist-to-hip ratio (+ 0.58 for men, + 0.52 for women)(P < 0.0001 for all correlations). In a regression analysis including the anthropometric measurements and the risk values, the sagittal diameter was the strongest measure of cardiovascular risk in both men and women. CONCLUSIONS: Among both men and women in this study the sagittal abdominal diameter showed stronger correlations to cardiovascular risk and to other risk factors in the metabolic syndrome than other anthropometric variables such as waist circumference, waist-to hip ratio and BMI.

Silicone-adjustable gastric banding: disappointing results.

BACKGROUND: Silicone-adjustable Gastric banding (SAGB) has been popularized as a minimally invasive, completely reversible surgical treatment for morbid obesity. We report here our 3-year experience of SAGB with special reference to complications and side-effects. METHODS: There were 90 patients in total, of whom 72 were women. Median age was 42 (range, 20-68) years and median body mass index (BMI) was 43 (range, 34-57) kg/m2. Laparoscopy was attempted to position the band in 63 cases but had to be converted to laparotomy in 16 (25%). Twenty-seven patients were laparotomized. We used the Swedish band (AB Obtech) throughout the series. In addition to regular clinic visits, patients were followed-up with upper gastrointestinal series 6 months postoperatively and gastroscopy after 2 years or earlier when symptomatic. RESULTS: Median BMI decreased to 32 kg/m2 after 12 months and to 31 kg/m2 after 24 months. With a median follow-up time of 35 months (range, 22-48), 32 patients (35%) have been re-operated usually with removal of the balloon system and conversion into a Roux-en-Y gastric bypass. The most common reasons for re-operation were band erosion (n = 10) and erosive esophagitis (n = 14). Additional indications for re-operation included pouch dilatation, invagination of distal gastric wall through the band, leakage from the balloon, patient dissatisfaction, and severe allergic reaction. When questioned 2 years postoperatively more than half of the patients reported vomiting, heartburn and regurgitation but 78% still pronounced themselves satisfied with the operation. Esophagitis was found in 56% of the patients at gastroscopy after 2 years. CONCLUSION: SAGB could be positioned with laparoscopy in 75% of the cases but the incidence of complications and side-effects postoperatively has been high.

Atherogenic lipid fractions are related to ionized magnesium status.

The plasma concentration of ionized magnesium (iMg++), the serum total magnesium concentration (tMg), and lipoprotein status were assessed in 29 elderly men with impaired insulin sensitivity but who were otherwise healthy and not receiving antidiabetic pharmacologic treatment. Plasma iMg++ was inversely correlated with serum concentrations of VLDL cholesterol (r = -0.39, P < 0.04), LDL cholesterol (r = -0.57, P < 0.002), total cholesterol (r = -0.55, P < 0.002), VLDL triacylglycerol (r = -0.36, P < 0.05), LDL triacylglycerol (r = -0.48, P < 0.01), and total triacylglycerol (r = -0.41, P < 0.03). The serum total magnesium concentration also tended to be inversely correlated with these lipid fractions, but not significantly so. Furthermore, iMg++ was inversely correlated with the apolipoprotein B concentration (r = -0.56, P < 0.002) and with the ratio of apolipoprotein B to A-I in serum (r = -0.58, P < 0.001). The corresponding values for tMg were r = -0.37 (P = 0.05) and r = -0.37 (P = 0.05), respectively. Insulin increment and the area under the insulin curve during an intravenous glucose tolerance test were inversely correlated with iMg++ [r = -0.56 (P < 0.01) and r = -0.64 (P < 0.0005), respectively], but were not significantly correlated with tMg. Insulin-mediated glucose uptake and the insulin sensitivity index during the hyperinsulinemic euglycemic clamp test were not significantly correlated with tMg (r = 0.05 and 0.12, respectively; NS) nor with iMg++ (r = 0.23 and 0.31, respectively; NS). Atherogenic lipid fractions and some glucometabolic variables were more closely correlated with iMg++ than with tMg.

The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up.

A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970-1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970-1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL/HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced delta 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

Serum alpha tocopherol concentrations and cholesterol ester fatty acid composition in 70-year-old men reflect those 20 years earlier.

OBJECTIVE: It has been suggested that low serum alpha tocopherol concentrations and a low proportion of polyunsaturated fatty acids in the serum cholesterol esters may be associated with a high risk of developing coronary heart disease. DESIGN AND SUBJECTS: In this study the intraindividual reproducibility (biological 'tracking') of these variables was studied in 855 men at the ages of 50 and 70 years. RESULTS: The lipid adjusted tocopherol concentration was positively correlated (r = 0.28, P < 0.0001) between 50 and 70 years of age. Also the proportions of the serum cholesterol ester fatty acids were positively correlated between the same ages with r = 0.31 (P < 0.0001) for palmitic, r = 0.45 (P < 0.0001) for linoleic, and r = 0.58 (P < 0.0001) for arachidonic acid. The body weights of the men at 50 and 70 years of age were strongly correlated (r = 0.78, P < 0.0001). CONCLUSIONS: The tocopherol concentrations and the fatty acid composition are related to vitamin intake and to the dietary fat quality, respectively, and may be useful markers in prospective studies of diseases and of development of diseases. The correlations between the proportions of fatty acids and the body weights, respectively at the ages of 50 and 70 indicate, that changes in diet and body weight in men are probably relatively limited between these years.

Gamma, but not alpha, tocopherol levels in serum are reduced in coronary heart disease patients.

OBJECTIVES: Low concentrations of alpha tocopherol are claimed to be associated with an increased prevalence of coronary heart disease. This study was undertaken to see whether measurements of serum tocopherol concentrations can contribute to discrimination between subjects with and without coronary heart disease. SETTING: All patients had been referred to the department of cardiology of the University Hospital in Uppsala, Sweden. SUBJECTS: Male patients (n = 69) below 60 years of age with coronary heart disease (CHD) and healthy age-matched reference subjects (n = 138) were compared. RESULTS: Lipid-corrected alpha tocopherol concentrations did not differ significantly between the groups, but the CHD group had a lower mean concentration of gamma tocopherol and a higher alpha/gamma ratio. In a stepwise logistic regression analysis, the LDL/HDL ratio was the best independent discriminator between the groups, followed by the proportion of palmitic acid in the cholesterol esters and the alpha/gamma tocopherol ratio. CONCLUSIONS: The lower gamma tocopherol concentration and the high ratio between alpha and gamma tocopherol in the CHD group indicate a difference in antioxidative status between CHD patients and healthy subjects. The lipid-lowering treatment of these CHD patients is far from optimal.

Similar effects of rapeseed oil (canola oil) and olive oil in a lipid-lowering diet for patients with hyperlipoproteinemia.

OBJECTIVE: To compare the metabolic effects of a lipid-lowering diet containing either low erucic rapeseed (canola) oil or olive oil. METHODS: Twenty-two hyperlipidemic patients participated in a cross-over study comprising two consecutive 3.5-week treatment periods. The participants were free-living throughout the study period, visiting the metabolic clinic initially and at the end of each treatment period for weighing and blood sampling. All food was prepared daily and weighed out for each individual appropriate to his/her energy requirement. RESULTS: Total serum cholesterol, low-density lipoprotein and the ratio between low-density and high-density lipoprotein cholesterol decreased to the same extent on the two diets tested, as did the apolipoproteins B, A-I and Lp(a). After adjustment for body weight changes, most of the reported effects remained virtually unaltered. However, there was a slightly greater decrease in low-density lipoprotein cholesterol with the diet containing rapeseed oil (-17%, p < 0.001) than with the olive oil diet (-13%, p < 0.01) with p < 0.04 for the difference between diets. Also, the intravenous glucose tolerance improved to a similar extent on both diets. CONCLUSIONS: The results indicate that lipid-lowering diets containing either rapeseed oil or olive oil have similar effects on serum lipoprotein concentration and glucose tolerance in hyperlipidemic subjects.

A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia.

In a double-blind, randomized crossover study, 29 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hyperlipoproteinemia were treated with gemfibrozil (1,200 mg/d) or simvastatin (10 mg/d) for 4 months. After gemfibrozil treatment, the insulin concentration was increased during the major part of the intravenous glucose tolerance test (IVGTT) and during the hyperinsulinemic euglycemic clamp. Similar but less pronounced elevations were caused by simvastatin. Insulin sensitivity decreased by 27% and 28% during gemfibrozil and simvastatin treatment, respectively. Low-density lipoprotein (LDL) cholesterol was decreased with simvastatin treatment by 24%. The LDL cholesterol level was not changed by gemfibrozil, but very-low-density lipoprotein (VLDL) cholesterol was reduced by 40%. The VLDL triglyceride concentration was reduced to a significantly greater extent by gemfibrozil. After gemfibrozil treatment, lipoprotein(a) [Lp(a)] was decreased by 24%, and the plasma free fatty acid (FFA) concentration was increased by 20% and skeletal muscle lipoprotein lipase activity (LPLA) by 37%. Although simvastatin more effectively decreased LDL cholesterol levels and the LDL to high-density lipoprotein (HDL) ratio, it cannot be claimed unreservedly that this drug is necessarily preferable in NIDDM patients. Gemfibrozil improved triglyceride removal and decreased VLDL concentrations, with qualitative changes in LDL. The apparent effects on insulin sensitivity are difficult to evaluate and need further study.

Malondialdehyde concentration in plasma is inversely correlated to the proportion of linoleic acid in serum lipoprotein lipids.

It has been suggested that the susceptibility of low density lipoprotein (LDL) to oxidative stress depends on the balance between its contents of polyunsaturated fatty acids and antioxidants. In a healthy reference population (n = 103), the plasma concentration of malondialdehyde (MDA) (mean 0.86, range 0.50-1.27 mumol/l) was positively correlated to the serum concentrations of LDL cholesterol (r = 0.31, P = 0.001), very low density lipoprotein triglycerides (r = 0.25, P = 0.009) and apolipoprotein B (r = 0.23, P = 0.03), and negatively correlated to lipid corrected alpha tocopherol in serum (r = -0.22, P = 0.02) and lipoprotein(a) (Lp(a)) (r = -0.26, P = 0.01). Plasma MDA was negatively correlated to the content of linoleic acid in the serum lipoprotein phospholipids (r = -0.35, P = 0.0008). In a stepwise regression analysis 12% of the variation in plasma MDA was explained by variations in the content of linoleic acid and 27% after addition of Lp(a) and abdominal sagittal diameter. The significant negative relation between plasma MDA and the amount of linoleic acid in the lipoprotein lipids indicates that other factors, e.g. the availability of anti-oxidants and the lipoprotein metabolism, may be of greater importance for intravascular lipid peroxidation than the proportion of polyunsaturated fatty acids in the lipoprotein lipids.

A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects.

The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P < 0.001), respectively, on the rapeseed oil diet and by 16%, 14%, and 13% (P < 0.001) on the sunflower oil diet. Serum triglycerides decreased more markedly (by 29%, P < 0.001) on the sunflower oil than on the rapeseed oil diet (14%, P < 0.01). The n-3 fatty acids (20:5 and 22:5) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet.

Tocopherol concentrations in adipose tissue. Relationships of tocopherol concentrations and fatty acid composition in serum in a reference population of Swedish men and women.

The tocopherol concentrations in serum and adipose tissue were studied in relation to the fatty acid composition and clinical characteristics in 110 subjects. The tocopherol concentrations in adipose tissue showed large interindividual variations and were positively correlated to those in serum (r = 0.24-0.31, P < 0.01) but did not increase with age. The ratio between alpha- and gamma-tocopherol in adipose tissue was only about half of that in serum. In serum, but not in adipose tissue, the alpha-tocopherol and linoleic acid concentrations were positively correlated. Serum apolipoprotein B was inversely correlated to lipid-corrected serum alpha-tocopherol (r = -0.22, P = 0.03), indicating decreasing oxidative protection with increasing blood lipids. Measurement of the serum tocopherol concentration in addition to that of the serum lipoprotein concentration may be of value in estimating the risk for coronary heart disease. Whether measurement of the tocopherol concentration in adipose tissue has any advantage over that in serum remains to be determined.