Is the association between dietary fat intake and insulin resistance modified by physical activity?

The rising prevalence of type 2 diabetes, a condition associated with insulin resistance, is commonly attributed to changes in dietary patterns and physical activity levels in susceptible populations. However, few studies have described the independent effects of dietary intake and physical activity on the degree of insulin sensitivity within populations or examined the possibility of interactions between dietary factors and physical activity. This study was undertaken to describe the relationship between the quantity and pattern of dietary fat intake on fasting insulin levels (a marker of insulin sensitivity) and to investigate whether the association was modified by physical activity. A cross-sectional study of 815 nondiabetic men and women (30 to 71 years) recruited from a population-based sampling frame was undertaken. Diet was characterized using a semiquantitative food frequency questionnaire. Physical activity level (PAL), the ratio of total energy expenditure to basal metabolic rate, was estimated using individually calibrated heart rate monitoring, a method previously shown to be an objective and valid method for assessing total energy expenditure. In a linear regression model adjusted for total energy intake, total fat intake bordered on a significant association with fasting insulin (b = 0.000081; P =.058), and the polyunsaturated to saturated fat ratio (P:S ratio) of the diet was negatively associated with fasting insulin concentration (b = -0.37, P <.001). A negative association was observed between the PAL and fasting insulin (b = -0.12, P =.025). The association of the P:S ratio and PAL with fasting insulin remained significant when adjusted for each other and for total fat, total energy intake, body mass index (BMI), waist-to-hip ratio (WHR), age, sex, family history of diabetes, smoking status, and alcohol intake (P:S ratio, b = -0.24, P =.003; PAL, b = -0.13; P =.007). The association with total fat intake was no longer significant in this multivariate model (b = 6.7 x 10(-6); P =.858). There was no evidence for an interaction between total dietary fat intake and PAL (b = -0.000048; P =.243) or between the P:S ratio and PAL (b = -0.013; P =.949). These data demonstrate an independent association between the P:S ratio of the diet, the overall level of physical activity, and the fasting insulin concentration, a marker of insulin sensitivity. There was no evidence that the association between dietary fat intake and insulin resistance was modified by physical activity. The findings provide further support for efforts to promote increases in overall physical activity and modifications in the pattern of dietary fat intake in the whole population.     

Relationship of dietary fat and serum cholesterol ester and phospholipid fatty acids to markers of insulin resistance in men and women with a range of glucose tolerance

High-fat diets are associated with insulin resistance, however, this effect may vary depending on the type of fat consumed. The purpose of this study was to determine the relationship between intakes of specific dietary fatty acids (assessed by 3-day diet records and fatty acid composition of serum cholesterol esters [CEs] and phospholipids [PLs]) and glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Nineteen men and 19 women completed the study. Nine subjects had type 2 diabetes or impaired glucose tolerance. Fasting insulin correlated with reported intakes of total fat (r = .50, P < .01), monounsaturated fat (r = .44, P < .01), and saturated fat (r = .49, P < .01), but not with trans fatty acid intake (r = .11, not significant [NS]). Fasting glucose also correlated with total (r = .39, P < .05) and monounsaturated fat intakes (r = .37, P < .05). In multivariate analysis, both total and saturated fat intake were strong single predictors of fasting insulin (R2 approximately .25), and a model combining dietary and anthropometric measures accounted for 47% of the variance in fasting insulin. Significant relationships were observed between fasting insulin and the serum CE enrichments of myristic (C14:0), palmitoleic (C16:1), and dihomo-gamma-linolenic (C20:3n-6) acids. In multivariate analysis, a model containing CE 14:0 and percent body fat explained 45% of the variance in fasting insulin, and C14:0 and age explained 30% of the variance in fasting glucose. PL C20:3n-6 explained 30% of the variance in fasting insulin, and a model including PL C18:1n-11 cis, C20:3n-6, age and body fat had an R2 of .58. In conclusion, self-reported intake of saturated and monounsaturated fats, but not trans fatty acids, are associated with markers of insulin resistance. Furthermore, enhancement of dihomo-gamma-linolenic and myristic acids in serum CE and PL, presumably markers for dietary intake, predicted insulin resistance.     

Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men.

AIMS: Dietary fatty acid intake is reflected in serum fatty acid composition. Studies prospectively investigating serum fatty acids and development of impaired fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We assessed the association of serum fatty acid composition with development of IFG or DM. METHODS: Middle-aged normoglycaemic men (n = 895) participating in a prospective cohort study were followed up after 4 years. RESULTS: At baseline proportions of serum esterified and non-esterified saturated fatty acids were increased and polyunsaturated fatty acids decreased in men who after 4 years had developed IFG (n = 56) or DM (n = 34). No differences in dietary fatty acid composition as recorded in 4-day dietary records were noted. In logistic regression analyses adjusting for age; obesity; and fasting lipid, glucose and insulin concentrations, men with proportions of non-esterified and esterified linoleate in the upper third had nearly half the risk for IFG or DM compared with the lower third. In covariate analyses, baseline non-esterified linoleate proportions were associated with changes in fasting insulin and glucose concentrations over the 4-year follow-up. Baseline esterified fatty acid composition was also associated with changes in insulin. CONCLUSIONS: High serum linoleate proportions decreased the risk of developing IFG or DM in middle-aged men over a 4-year follow-up, possibly mediated in part by insulin resistance. These findings support recommendations to substitute vegetable fat for animal and dairy fat in the prevention of disturbances of glucose and lipid metabolism.     

Differential regulation of insulin action and tumor necrosis factor alpha system activity by metformin

BACKGROUND: Tumor necrosis factor alpha has a key role in insulin resistance. We study the effects of metformin on glucose tolerance, insulin resistance, beta cell function, and soluble tumor necrosis factor receptor (sTNFR) levels. METHODS: We performed a double-blind, randomized metformin-placebo study. Twenty-three subjects with impaired glucose tolerance or impaired fasting glucose were studied. Oral glucose tolerance, homeostasis model assessment, and continuous infusion of glucose with model assessment tests were used to evaluate glucose tolerance, insulin sensitivity, and beta cell function, respectively. Soluble tumor necrosis factor receptor levels were measured before and after therapy. Repeated measures analysis of variance was used for statistical analysis. RESULTS: After 12-week treatment, fasting glucose (110.1 +/- 9.9 to 98.9 +/- 15.7 mg/dl, P < .001), fasting insulin (11.6 +/- 5.4 to 8.8 +/- 3.5 mU/L, P = .05), fasting C-peptide (2.5 +/- 0.7 to 1.8 +/- 0.5 ng/mL, P < .05), and achieved C-peptide (5.2 +/- 1.2 to 4.2 +/- 1 ng/mL, P < .05) levels decreased in the metformin group. In addition, there was an improvement in insulin sensitivity (37.4% +/- 15.2% to 50.4% +/- 23.2%, P < .05) with unchanged sTNFR1 (2.0 +/- 0.8 to 2.3 +/- 1.2 microg/L, P = NS) and sTNFR2 (4.8 +/- 1.7 to 4.4 +/- 1.2 microg/L, P = NS) levels. CONCLUSIONS: Metformin is able to reverse insulin resistance and hyperglycemia in high-risk subjects for type 2 diabetes mellitus independently of the effects on tumor necrosis factor alpha system activity.     

Insulin resistance as a modifier of the relationship between dietary fat intake and weight gain

OBJECTIVE: To investigate whether insulin resistance modifies the rate of weight gain associated with a high percent of energy intake from dietary fat. DESIGN: Longitudinal, observational population study. SUBJECTS: A total of 782 nondiabetic Hispanic and non-Hispanic white free-living adult residents of the San Luis Valley in Colorado. MEASUREMENTS: Subjects were seen up to three times over a 14-y period. Weight, height, fasting insulin and glucose, diet by 24 h recall, and self-reported physical activity were collected at each visit. RESULTS: Percentage of energy intake from dietary fat was positively associated with weight gain over time (P=0.0103). High intake of dietary fat was more strongly related to weight gain in women than in men, and in those with lower total energy intake levels. The relationship between weight change and relative macronutrient intake also varied by baseline insulin sensitivity (P=0.0025). Weight gain over time in individuals with relative insulin resistance at baseline, as measured by QUICKI, was the greatest among those who consumed a higher percent of energy from fat. CONCLUSION: Percentage of total intake from dietary fat predicts weight change independent of total energy intake. Nondiabetic, insulin-resistant individuals are particularly susceptible to the weight gain associated with high levels of dietary fat intake. Further investigation into the relationship between insulin resistance, diet, and weight gain is warranted.     

Association between diet, lifestyle, metabolic cardiovascular risk factors, and plasma C-reactive protein levels

Increased C-reactive protein (CRP) levels have been associated with several of the components of the metabolic syndrome, but the direct influence of diet and lifestyle factors on CRP levels remains largely unknown. The purpose of the present study was to investigate the association between CRP and diet and lifestyle factors. Plasma CRP levels were determined by a highly sensitive enzyme-linked immunosorbent assay (ELISA) in 760 participants in the beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS). In accordance with previous findings, increased levels of CRP were associated with high body mass index (BMI) (P = .012), triglycerides (P = .001), systolic blood pressure (P = .019), cholesterol/high-density lipoprotein (HDL) ratio (P = .009), and low HDL cholesterol (P = .001). CRP was also increased in smokers (P = .023) and in subjects with a low vitamin C intake (P = .018). When men and women were analyzed together, there were no significant associations between CRP and dietary intake of total calories, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, fiber, vitamin E, carotene, or selen, or in physical activity. However, in the female subgroup weak inverse relations were observed between CRP and the intake of total fat (r = -0.13, P = .011), saturated fat (r = -0.13, P = .011), monounsaturated fat (r = -0.13, P = .010), polyunsaturated fat (r = -0.14, P = .007), and n-3 PUFA (r = -0.14, P = .004). Stratified factor analyses in smoking subgroups, obese, and in under-reporters of energy, largely confirmed the results although in male never-smokers a combination of high fiber vitamin C/beta carotene intake was associated with low CRP levels. These observations suggest that CRP levels are only marginally associated with individual dietary and lifestyle factors. Surprisingly, a higher intake of fat tended to be associated with lower CRP values among women.     

Nutrition and physical activity in Asian Indians with non-alcoholic fatty liver: A case control study

AimWe tested the hypothesis that Asian Indians with non-alcoholic fatty liver disease (NAFLD) would have imbalanced diets and lower intensity of physical activity than those without NAFLD.MethodsWe studied dietary intake, intensity of physical activity and anthropometric and metabolic profiles in subjects with NAFLD and in healthy controls. Complete clinical, biochemical, dietary and physical activity profiles were studied for 169 cases and 173 controls in a prospective manner. Bivariate and multivariate analyses were carried out to identify the predictors of NAFLD [odds ratio (OR) and 95% confidence intervals (95%CI)].ResultsThe mean dietary intakes of total energy, carbohydrate, protein, total fat, saturated fat and total cholesterol were significantly higher, while intake of monounsaturated fatty acids and polyunsaturated fatty acids was significantly lower in cases as compared to controls (p < 0.01 for all). Further, mean physical activity in a day (expressed as MET.Minutes) and total energy expenditure were significantly lower in cases than in controls (33.3 ± 3.6 vs.36.2 ± 0.5, p = 0.001 and 2707.6 ± 505.6 vs. 2904.3 ± 690.3, p = 0.02, respectively). On multivariate analysis, percentage dietary total fat intake (OR: 13.4; 95% CI: 4.6–39.3, p = 0.001), homeostatis model assessment for insulin resistance (OR: 6.9; 95% CI: 3.2–14.8, p = 0.001) abdominal obesity (OR: 2.7; 95% CI: 1.5–5.0, p = 0.001) and high serum triglycerides (OR: 2.1; 95%CI: 1.2–3.8, p = 0.007) were associated with an increased risk for development of NAFLD.ConclusionDecrease in intake of total dietary fats and improvement of insulin resistance, abdominal obesity and blood triglycerides should be important measures for management of NAFLD in Asian Indians in north India.     

Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity

Aims/hypothesis: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. Methods: A total of 17 subjects – six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes – were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. Results: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. Conclusion/interpretation: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes. [Diabetologia (2002) 45: 369–377] Received: 3 August 2001 and in revised form: 26 November 2001     

Habitual dietary intake versus glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women.

OBJECTIVE: The major aim was to study the relation between habitual dietary intake and glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women. Dietary intake was also compared between women with normal (NGT) or impaired glucose tolerance (IGT). DESIGN: Habitual dietary intake was studied using a modified diet history method, from which the energy, carbohydrate, fat and protein intake was calculated. Glucose tolerance was determined as the 2 h glucose value after a 75 g oral glucose tolerance test. Insulin sensitivity was studied with a euglycemic, hyperinsulinaemic clamp, whilst insulin secretion was measured as the acute (2-5 min) response to iv arginine (5 g) at fasting, 14 and >25 mmol L(-1) glucose. SETTING: Clinical research unit at the University Hospital in Malmo, Sweden. Subjects. A total of 74 women (mean+/-SD age 58.7+/-0.4 years). RESULTS: In the entire group, the 2 h glucose level correlated with polyunsaturated fat intake (PUFA, r = 0.41, P < 0.001), and negatively with carbohydrate intake (r = -0.23, P = 0.05). The relation between 2 h glucose and PUFA was independent of body fat content and insulin sensitivity in a multivariate model. Insulin sensitivity correlated with energy intake (r = 0.31, P = 0.007) and PUFA (r = -0.27. P = 0.022). However, these correlations were not significant after adjustment for body fat content in a multivariate model. There were no correlations between insulin secretory variables and habitual dietary intake. Of the 74 women, 60 had NGT and 14 had IGT. The NGT and IGT groups did not differ in intakes of total energy, carbohydrate or protein. The IGT women had higher intake of PUFA (P = 0.003), whilst the total, saturated and monounsaturated fat intake did not differ between the groups. CONCLUSION: Dietary parameters are not independently associated with insulin sensitivity or insulin secretion in postmenopausal women. Furthermore, dietary habits are largely similar in women with NGT and IGT, although subtle differences cannot be excluded due to the small study size. Therefore, habitual intake of total carbohydrate or total fat seems not to be the major determinant of glucose tolerance in nondiabetic Caucasian postmenopausal women.     

High saturated fat and low starch and fibre are associated with hyperinsulinaemia in a non-diabetic population: The San Luis Valley Diabetes Study

Summary A geographically based sample of 1069 Hispanic and non-Hispanic white persons aged 20–74 years, living in southern Colorado and who tested normal on an oral glucose tolerance test (World Health Organization criteria) were evaluated to determine associations of dietary factors with fasting serum insulin concentrations. Subjects were seen for up to three visits from 1984 to 1992. A 24-h diet recall and fasting insulin concentrations were collected at all visits. In longitudinal data analysis, lower age, female gender, Hispanic ethnicity, higher body mass index, higher waist circumference, and no vigorous activity were significantly related to higher fasting insulin concentrations. High total and saturated fat intake were associated with higher fasting insulin concentrations after adjusting for age, sex, ethnicity, body mass index, waist circumference, total energy intake and physical activity. Dietary fibre and starch intake were inversely associated with fasting insulin concentrations. No associations with fasting insulin concentrations were observed for monounsaturated fat, polyunsaturated fat, sucrose, glucose and fructose intake. Associations were similar in men and women and for active and inactive subjects, though associations of fibre and starch intake with insulin concentrations were strongest in lean subjects. These findings support animal studies and a limited number of human population studies which have suggested that increased saturated and total fat intake and decreased fibre and starch intake increase fasting insulin concentrations and may also increase insulin resistance. These findings, which relate habitual macronutrient consumption to hyperinsulinaemia in a large population, may have implications for studies attempting primary prevention of non-insulin-dependent diabetes mellitus. [Diabetologia (1997) 40: 430–438] Received: 6 August 1996 and in revised form: 17 December 1996     

Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level?

Peroxisome proliferator-activated receptor gamma (PPARgamma) has a role in controlling adipogenesis and insulin sensitivity. Previous studies have suggested that a common polymorphism (Pro12Ala) in the PPARgamma-2 isoform of this gene may be associated with markers of insulin resistance. We have previously shown that in combination, the relationships with fasting insulin of dietary polyunsaturated to saturated fatty acid ratio (P:S ratio) and physical activity are additive. We have also demonstrated that the association between P:S ratio and fasting insulin level is modified by the Pro12Ala genotype. The purpose of the present study was to investigate whether the Pro12Ala genotype modified the combined relationships of P:S ratio and physical activity level (PAL) on fasting insulin concentration. A population-based cohort of 506 Caucasian men and women aged 31 to 71 years was genotyped for the Pro12Ala polymorphism. P:S ratio was assessed by food-frequency questionnaire (FFQ) and PAL was estimated from 4 days of free-living heart rate monitoring following individual calibration of heart rate against energy expenditure during an exercise stress test. The combined associations of PAL and P:S ratio on fasting insulin level were examined stratified by Pro12Ala genotypes in a dominant model for the Ala allele. Among Pro allele homozygotes, there was no interaction between PAL and P:S ratio on fasting insulin (P =.929). However, in carriers of the Ala allele the association of P:S ratio with fasting insulin was modified by activity level (interaction P = 0.038). In those who were inactive and carried the Ala allele, the age-, sex-, and body mass-adjusted relationship between P:S ratio and log insulin was not significant (beta = -0.03, P =.93). In contrast, in physically active Ala carriers, the association of P:S ratio with log fasting insulin was highly significant (beta = -0.93, P =.004). In conclusion, this study examined the modification by PPARgamma genotype of the association between energy expenditure, P:S ratio, and fasting insulin level, a measure of insulin resistance. These data show that in Pro allele homozygotes the combined associations of P:S ratio and PAL are additive. In contrast, in Ala allele carriers, PAL modifies the association between P:S ratio and fasting insulin level in a multiplicative manner.     

Metabolic and anthropometric evaluation of insulin resistance in nondiabetic patients with nonalcoholic steatohepatitis

OBJECTIVES: Insulin resistance is nearly universal in patients with nonalcoholic steatohepatitis (NASH) when tested by glucose tolerance tests or clamp methods. However, the pattern of insulin resistance in these patients after a physiological challenge is unknown. We conducted a study to characterize the metabolic response to a mixed meal in nondiabetic patients with NASH (NDN) and to identify anthropometric determinants of insulin resistance in these patients. METHODS: Serum insulin, C-peptide, glucose, and free fatty acid (FFA) levels were measured at 0, 30, 60, 90, and 120 min after a 500-kcal standard meal in 18 NDN and 18 age-, gender-, and body mass index (BMI)-matched controls. Correlations were made between insulin resistance and various anthropometric, calorimetric, and serological variables. RESULTS: Compared with controls, NDN had significantly higher levels of insulin and C-peptide at baseline and after the mixed meal. However, glucose levels were not different either at baseline or after the meal. NDN had higher fasting levels of FFA than the controls (459 +/- 190 vs 339 +/- 144 micro mol/L, respectively, p = 0.03); however, meal-induced suppression in lipolysis was similar between the two groups (39 +/- 113% vs 46 +/- 60%, p = 0.8). Insulin resistance was significantly correlated with BMI (r = 0.39, p = 0.02) and visceral fat (r = 0.50, p = 0.004). Whereas BMI, percent total body fat, and subcutaneous abdominal fat were similar between the groups, the NASH group had significantly higher percent visceral fat compared with controls (28 +/- 10% vs 22 +/- 14%, p = 0.02). CONCLUSIONS: NDN are significantly hyperinsulinemic, both at fasting and after the mixed meal; however, their glucose homeostasis and suppression in lipolysis after a meal challenge are maintained. Insulin resistance in these patients is likely related to their higher visceral fat mass.     

Dietary fat type (virgin olive vs. sunflower oils) affects age-related changes in DNA double-strand-breaks, antioxidant capacity and blood lipids in rats

This study was designed to investigate the possible effect on DNA double-strand breaks, antioxidant capacity and blood lipids of feeding rats lifelong with two different dietary fat sources: virgin olive oil (rich in the monounsaturated oleic acid) or sunflower oil (rich in the polyunsaturated linoleic acid). No changes in mean or maximal lifespan were observed. Overall, aging led to increased levels of plasma cholesterol, triglycerides, phospholipids, total lipids, polyunsaturated fatty acids and DNA double-strand breaks. All these parameters were higher in animals fed on sunflower oil diet. Aging diminished total antioxidant capacity with both diets, but in a lower extension for virgin olive oil diet. A very good inverse correlation (r= -0.715; P < 0.01, for sunflower oil group and r= -0.535; P < 0.01 for virgin olive oil group) between DNA damage and total antioxidant capacity was found. These results allow to conclude that dietary fat type should be considered in studies on aging, since the intake of oils with different polyunsaturation levels directly modulates total antioxidant capacity of plasma, DNA damage to peripheral blood lymphocytes and lead to important changes at the lipid metabolism level. In the present study best results were found after intake of virgin olive oil, which suggest the possible use of that edible oil to provide a healthier aging.     

Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults

AIMS/HYPOTHESIS: Epidemiological research indicates that long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) improve insulin resistance. The aim of this study was to investigate the effects of seafood consumption on insulin resistance in overweight participants during energy restriction. METHODS: In this 8 week dietary intervention, 324 participants (20-40 years, BMI 27.5-32.5 kg/m(2), from Iceland, Spain and Ireland) were randomised by computer to one of four energy-restricted diets (-30E%) of identical macronutrient composition but different LC n-3 PUFA content: control (n = 80; no seafood; single-blinded); lean fish (n = 80; 150 g cod, three times/week); fatty fish (n = 84; 150 g salmon, three times/week); (4) fish oil (n = 80; daily docosahexaenoic/eicosapentaenoic acid capsules, no other seafood; single-blinded). Fasting glucose, insulin, adiponectin, plasma triacylglycerol and fatty acids in erythrocyte membrane were measured at baseline and endpoint. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Linear models with fixed effects and covariates were used to investigate the effects of seafood consumption on fasting insulin and HOMA-IR at endpoint in comparison with the control group. RESULTS: Of the participants, 278 (86%) completed the intervention. Fish oil intake was a significant predictor of fasting insulin and insulin resistance after 8 weeks, and this finding remained significant even after including weight loss, triacylglycerol reduction, increased LC n-3 PUFA in membranes or adiponectin changes as covariates in the statistical analysis. Weight loss was also a significant predictor of improvements. CONCLUSIONS/INTERPRETATION: LC n-3 PUFA consumption during energy reduction exerts positive effects on insulin resistance in young overweight individuals, independently from changes in body weight, triacylglycerol, erythrocyte membrane or adiponectin. Trial registration: ClinicalTrials.gov NCT00315770.     

Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function.

OBJECTIVES: The purpose of this study was to investigate the influence of dietary fatty acids on the anti-inflammatory properties of high-density lipoproteins (HDL) and vascular function. BACKGROUND: The effect of dietary fatty acids on atherogenesis remains uncertain. METHODS: Fourteen adults consumed an isocaloric meal containing either a polyunsaturated or a saturated fat on 2 occasions. The effects of post-prandial HDL on endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined. Flow-mediated dilation (FMD) and microvascular reactivity were assessed before and 3 and 6 h after the meal. RESULTS: Plasma triglycerides, insulin, and nonesterified fatty acids rose after the meals. The HDL collected 6 h after the saturated meal were less effective than HDL isolated from fasting plasma in terms of their ability to inhibit expression of ICAM-1 and VCAM-1, whereas HDL collected 6 h after the polyunsaturated meal had an inhibitory activity that was greater than that of HDL collected from fasting plasma (p < 0.004 and p = 0.01 for comparison of effect of meals on ICAM-1 and VCAM-1, respectively). Post-hyperemic microvascular flow significantly increased at 3 h after the polyunsaturated meal by 45 +/- 14% and by 21 +/- 11% after the saturated meal. The FMD decreased 3 h after the saturated meal by 2.2 +/- 0.9% (p< 0.05 compared with baseline) and by 0.9 +/- 1% after the polyunsaturated meal. CONCLUSIONS: Consumption of a saturated fat reduces the anti-inflammatory potential of HDL and impairs arterial endothelial function. In contrast, the anti-inflammatory activity of HDL improves after consumption of polyunsaturated fat. These findings highlight novel mechanisms by which different dietary fatty acids may influence key atherogenic processes.     

Liver fat in the metabolic syndrome

BACKGROUND: The liver, once fatty, overproduces components of the metabolic syndrome, such as glucose and lipids. The amount of liver fat in subjects with and without the metabolic syndrome has not been determined. It is unknown which clinically available markers best reflect liver fat content. MEASUREMENTS: Components of the metabolic syndrome as defined by the International Diabetes Federation and liver fat content by proton magnetic resonance spectroscopy were measured in 271 nondiabetic subjects (162 women, 109 men). In addition, other features of insulin resistance (serum insulin, C-peptide), intraabdominal and sc fat by magnetic resonance imaging, and liver enzymes (serum alanine aminotransferase and serum aspartate aminotransferase) were measured. RESULTS: Liver fat was 4-fold higher in subjects with [n = 116; median 8.2% (interquartile range 3.2-18.7%)] than without [n = 155; 2.0% (1.0-5.0%); P < 0.0001] the metabolic syndrome. This increase in liver fat remained significant after adjusting for age, gender, and body mass index. All components of the metabolic syndrome correlated with liver fat content. The best correlate was waist in both women (r = 0.59, P < 0.0001) and men (r = 0.56, P < 0.0001). Liver fat correlated significantly with serum alanine aminotransferase (r = 0.39, P < 0.0001 for women; r = 0.44, P < 0.0001 for men) and aspartate aminotransferase (r = 0.27, P = 0.0005 for women; r = 0.31, P = 0.0012 for men) concentrations. The best correlates of liver fat were fasting serum insulin (r = 0.61; P < 0.0001 for both women and men) and C-peptide (r = 0.62; P < 0.0001 for both women and men). CONCLUSIONS: Liver fat content is significantly increased in subjects with the metabolic syndrome as compared with those without the syndrome, independently of age, gender, and body mass index. Of other markers, serum C-peptide is the strongest correlate of liver fat.     

The influence of dietary fat on insulin resistance

Dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Although, in practice, obesity may complicate the relationship between fat intake and insulin resistance, clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. In addition, it appears that different types of fat have different effects on insulin action. Saturated and certain monounsaturated fats have been implicated in causing insulin resistance, whereas polyunsaturated and omega-3 fatty acids largely do not appear to have adverse effects on insulin action. Given the importance of insulin resistance in the development of diabetes and heart disease, establishing appropriate levels of fat in the diet is an important clinical goal.     

Ethnic differences in C-peptide/insulin/glucose dynamics in young pregnant women

There are ethnic differences in insulin secretion and resistance in healthy nondiabetic adults, children, and adolescents. It is not known whether these ethnic differences are also detectable during normal pregnancy. The objective of this study was to examine whether ethnic differences in glucose homeostasis (C-peptide/insulin/glucose dynamics) are present in nondiabetic pregnant women. Fasting serum C-peptide, insulin, and plasma glucose were measured in the second and third trimesters in 773 pregnant women (343 African-Americans, 312 Hispanics, and 118 Caucasians), and a 50-g oral glucose challenge test was performed in the third trimester. Significantly reduced C-peptide levels and C-peptide to insulin ratio and elevated fasting insulin to glucose ratios were observed in African-American women compared with Caucasians and/or Hispanics. Similar results were found after a 50-g glucose load. In addition, African-Americans had greater insulin and lower glucose levels at glucose challenge test. There were ethnic differences in insulin production and resistance in both fasting and glucose-stimulated conditions in normal young nondiabetic pregnant women.     

High-fat meal impairs vascular compliance in a subgroup of young healthy subjects

Postprandial hypertriglyceridemia impairs endothelial function and may possibly worsen vascular compliance by increasing oxidative stress. Large (C1) and small (C2) artery compliance, glucose, insulin, and triglycerides (TGs) were measured hourly for 6 hours in 18 young healthy volunteers after a low-fat meal and a high-fat meal, with and without antioxidant vitamins. C1 and C2 declined significantly for 6 hours after fat ingestion in 8 subjects ("fat reactors") and increased in 10 ("nonreactors"). Fat reactors had higher fasting and peak serum TGs after fat loading and increased baseline glucose and insulin levels and homeostasis model assessment of insulin resistance (HOMA(IR)). Fasting insulin correlated with C1 and C2 only in fat reactors. After fat intake, plasma nitric oxide metabolites decreased more in fat reactors than in nonreactors (17.0% +/- 5.1% vs 4.8% +/- 2.1%; P < .05). In fat reactors, pretreatment with antioxidant vitamins before the high-fat meal blunted the fall in C1 but not in C2. Compliance was unchanged after the low-fat meal. Normal weight young subjects with an insulin resistance phenotype show significantly decreased vascular compliance, increased postprandial TG peaks, and markedly reduced plasma nitric oxide metabolites after a high-fat meal.     

Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids in acquired total lipodystrophy: effects on hyperlipoproteinemia and endogenous insulin resistance

Previous studies have suggested that reduction of dietary fat intake, with or without caloric restriction, may lead to improvement in certain of the characteristic abnormalities that accompany total lipodystrophy (TLD). We have studied the effects of eucaloric medium chain triglyceride (MCT) substitution for dietary long chain fatty acids in a patient with acquired total lipodystrophy and unusual somatic and visceral anomalies. The patient exhibited insulin resistance, carbohydrate intolerance, striking fasting- and glucose-stimulated hyperinsulinemia, hyperglucagonemia, type V hyperlipoproteinemia, and lipoprotein lipase deficiency on a normal diet. Improvement in chylomicronemia, hypertriglyceridemia, and xanthomatosis occurred during eucaloric MCT substitution. Carbohydrate intolerance decreased and fasting immunoreactive glucagon and insulin concentrations fell 37% and 83%, respectively. Plasma triglyceride polyunsaturated fatty acid concentrations decreased to very low levels. With long term MCT feeding supplemented by polyunsaturated fatty acids, hepatomegaly has gradually decreased, while body weight has remained stable. The patient has not yet required insulin therapy. These observations suggest that the abnormalities in carbohydrate metabolism are closely linked to, and perhaps dependent on, the abnormalities in lipoprotein transport in TLD. Long chain triglyceride restriction and MCT supplementation should be attempted in additional patients with the features of TLD to determine whether this is a generally effective therapeutic approach.