Bengt Vessby

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319]

Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus

Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus.

Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men.

SummaryRecent data indicate that peripheral insulin sensitivity may be influenced by dietary fat quality and skeletal muscle phospholipid fatty acid composition. During a health survey of 70-year-old men insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique and the fatty acid composition of the serum cholesterol esters was determined (n=215) by gas liquid chromatography. In a subsample the fatty acids of the skeletal muscle phospholipids and triglycerides were determined after fine needle biopsy from m. vastus lateralis (n=39). The peripheral insulin sensitivity was significantly and negatively correlated to the proportion of palmitic (r=−0.31, p<0.001), palmitoleic (r=−0.25, p<0.001) and di-homo-γ-linolenic (r=−0.33, p<0.001) acids and positively to the content of linoleic (r=0.28, p<0.001) acid in the serum cholesterol esters. There was an even stronger negative relationship to the proportion of palmitic acid in the skeletal muscle phospholipds (r=−0.45, p<0.004). The fatty acid composition was also significantly related to insulin sensitivity in a stepwise multiple regression analysis in the presence of other clinical variables, which were associated with insulin action in univariate analysis. Thus, more than 51% of the variation of the insulin sensitivity was explained by an equation containing body mass index, serum triglyceride concentration and the content of palmitic acid in the skeletal muscle phospholipids. It is concluded that the fatty acid composition in serum and of the phospholipids of skeletal muscle may influence insulin action in elderly men.

Conjugated Linoleic Acid Supplementation in Humans—Metabolic Effects

Supplementation with conjugated linoleic acid (CLA) induces a number of physiological effects in experimental animals, including reduced body fat content, decreased aortic lipid deposition, and improved serum lipid profile. Controlled trials on the effects of CLA in humans have hitherto been scarce. The aim of this study was to evaluate the effects of supplementation with CLA in healthy humans on anthropometric and metabolic variables and on the fatty acid composition of serum lipids and thrombocytes. Fifty-three healthy men and women, aged 23–63 yr, were randomly assigned to supplementation with CLA (4.2 g/d) or the same amount of olive oil during 12 wk in a double-blind fashion. The proportion of body fat decreased (−3.8%, P<0.001) in the CLA-treated group, with a significant difference from the control group (P=0.050). Body weight, body mass index, and sagittal abdominal diameter were unchanged. There were no major differences between the groups in serum lipoproteins, nonesterified fatty acids, plasma insulin, blood glucose, or plasminogen activator inhibitor 1 (PAI-1). In the CLA group the proportions of stearic, docosatetraenoic, and docosapentaenoic acids increased in serum lipids and thrombocytes, while proportions of palmitic, oleic, and dihomoγ-linolenic acids decreased, causing a decrease of the estimated Δ-6 and Δ-9 and an increase in the Δ-5 desaturase activities. These results suggest that supplementation with CLA may reduce the proportion of body fat in humans and that CLA affects fatty acid metabolism. No effects on body weight, serum lipids, glucose metabolism, or PAI-1 were seen.

Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein: A Potential Link to Fatty Acid-Induced Insulin Resistance.

Background—Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t 10 c 12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance. Methods and Results—In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t 10 c 12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF2&agr; [F2-isoprostanes]), 15-ketodihydro PGF2&agr;, plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-&agr;, and interleukin-6 were assessed before and after treatment. Supplementation with t 10 c 12 CLA markedly increased 8-iso-PGF2&agr; (578%) and C-reactive protein (110%) compared with placebo (P <0.0001 and P <0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF2&agr;, but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism. Conclusions—t 10 c 12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t 10 c 12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.

Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men

Aims/hypothesisTypes of dietary fat have been related to components of the metabolic syndrome. Serum fatty acid composition mainly reflects dietary fat intake, but also endogenous fatty acid synthesis catalysed by Δ-desaturases. It is not known whether alterations of fatty acid composition or desaturase activities predict metabolic syndrome.Materials and methodsWe prospectively evaluated fatty acid composition in serum cholesteryl esters and estimated desaturase activities in 1,558 50-year-old men taking part in a population-based cohort study. The follow-up time was 20 years. Stearoyl-CoA desaturase (SCD-1), Δ6 (D6D) and Δ5 (D5D) desaturases were estimated as precursor to fatty acid ratios.ResultsHigh activity of estimated SCD-1 (odds ratio=1.29, p<0.05) and D6D (odds ratio=1.35, p<0.05), as well as low estimated D5D activity (odds ratio=0.71, p<0.001) predicted the development of metabolic syndrome (as defined by the National Cholesterol Education Program). The predictive value of D5D activity was independent of lifestyle factors (smoking, BMI and physical activity), whereas the risk associated with higher SCD-1 and D6D activities was mainly explained by obesity. Among those developing metabolic syndrome (119 out of 706) during follow-up, the proportions of fatty acids 14:0, 16:0, 16:1 (n−7), 18:1 (n−9), 18:3 (n−6) and 20:3 (n−6) were increased at baseline, while 18:2 (n−6) was decreased (p<0.05 for all).Conclusions/interpretationSerum fatty acid composition predicts the long-term development of the metabolic syndrome, and D5D activity may be particularly important in this process. Our results suggest a role of dietary fat quality in the development of metabolic syndrome, but the possibility that altered fatty acid composition, partly secondary to genetic or hormonal factors, should also be considered.

Desaturation and Elongation of Fatty Acids and Insulin Action

Abstract: Insulin resistance is characterized by specific changes of the composition of fatty acids in the serum lipids and in the skeletal muscle membranes. Impaired insulin sensitivity is associated with high proportions of palmitic (16:0) acid and low levels of linoleic (18:2 n‐6) acid in serum. In addition, there are apparent changes of the fatty acid desaturase activities, suggesting an increased activity of the Δ9 and Δ6 desaturases and a decreased activity of the Δ5 desaturase. The activity of the fatty acid desaturases is regulated by long‐chain polyunsaturated fatty acids and insulin and is probably also dependent on the degree of physical activity. A high ratio between arachidonic (20:4 n‐6) and dihomo‐gamma linolenic (20:3 n‐6) acid, as a measure of Δ5 desaturase activity, in the skeletal muscle phospholipids has been related to good insulin sensitivity. Available knowledge seems to indicate that the degree of saturation of the body lipids, and especially the proportion of palmitic acid in the lipid membranes, may be critical for insulin sensitivity. The strong relationships between the Δ5 desaturase activity, a high content of long‐chain polyunsaturated fatty acids in the skeletal muscle, and insulin sensitivity may be due to parallel effects of diet and/or physical activity on the fatty acid composition and on insulin sensitivity.

Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial

BACKGROUND: Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested.OBJECTIVE: To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders.METHODS: Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05±0.05; body mass index (BMI), 32±2.7 kg/m2 (mean±s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men recieved a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin.RESULTS: At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; −1.12, −0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups.CONCLUSIONS: These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.

Dietary fat and insulin action in humans

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16:0) and palmitoleic acids (16:1 n-7) and reduced levels of linoleic acid (18:2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20:3 n-6) and a reduced activity of the delta 5 desaturase, while the activities of the delta 9 and delta 6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of delta 5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.

The Risk to Develop NIDDM Is Related to the Fatty Acid Composition of the Serum Cholesterol Esters

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (w = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:ω-7), a low proportion of linoleic acid (18:2ω-6), and a relatively high content of γ-linolenic (18:3ω-6) and dihomo-γ-linolenic (20:3ω-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-γ-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.