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The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in young populations. However, there are inadequate data regarding diagnosis of NAFLD. We aimed to validate three scoring systems against a previous standard of suprailiac skinfold thickness for diagnosing NAFLD in population-based adolescents. Seventeen-year-old adolescents (n = 899), participating in the Raine Study, attended a cross-sectional follow-up. NAFLD was diagnosed using liver ultrasound. Scores for Fatty liver index (FLI), Hepatic Steatosis Index (HSI) and Zhejiang University index (ZJU index) were calculated. Diagnostic accuracy of these diagnostic tests was evaluated through discrimination and calibration. NAFLD was diagnosed 9% in males and 15% in females. The three scoring systems demonstrated better discrimination performance for NAFLD in males (AUC was FLI:0.82, HSI: 0.83 and ZJU index: 0.83) compared to females (AUC was FLI: 0.67, HSI: 0.67 and ZJU index: 0.67). Suprailiac skinfold performed better than the scoring systems (overall AUC: 0.82; male AUC:0.88; female AUC:0.73). FLI had best calibration performance. Suprailiac skinfold thickness was a better predictor of ultrasound-diagnosed NAFLD than the three diagnostic scoring systems investigated. The higher performance characteristics of the algorithmic scoring systems in males compared with females may have implications for use in population assessments. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that increasing intakes of nitrate-rich vegetables may be an effective approach to reduce blood pressure. Objective: Our primary aim was to determine whether daily consumption of nitrate-rich vegetables over 4 wk would result in lower blood pressure. Design: Thirty participants with prehypertension or untreated grade 1 hypertension were recruited to a randomized controlled crossover trial with 4-wk treatment periods separated by 4-wk washout periods. Participants completed 3 treatments in random order: 1) increased intake (~200 g/d) of nitrate-rich vegetables [high-nitrate (HN); ~150 mg nitrate/d], 2) increased intake (~200 g/d) of nitrate-poor vegetables [low-nitrate (LN); ~22 mg nitrate/d], and 3) no increase in vegetables (control; ~6mg nitrate/d). Compliance was assessed with the use of food diaries and by measuring plasma nitrate and carotenoids. Nitrate metabolism was assessed with the use of plasma, salivary, and urinary nitrate and nitrite concentrations. The primary outcome was blood pressure assessed by using 24-h ambulatory, home, and clinic measurements. Secondary outcomes included measures of arterial stiffness. Results: Plasma nitrate and nitrite concentrations increased with the HN treatment in comparison to the LN and control treatments (P<0.001). Plasma carotenoids increased with the HN and LN treatments compared with the control (P < 0.01). HN treatment did not reduce systolic blood pressure [24-h ambulatory--HN: 127.4 ± 1.1 mm Hg; LN: 128.6 ± 1.1 mm Hg; control: 126.2 ± 1.1 mm Hg (P = 0.20); home--HN: 127.4 ± 0.7 mm Hg; LN: 128.7 ± 0.7 mm Hg; control: 128.3 ± 0.7 mmHg (P=0.36); clinic--HN: 128.4±1.3 mm Hg; LN: 130.3 ± 1.3 mm Hg; control: 129.8 ± 1.3 mm Hg (P = 0.49)] or diastolic blood pressure compared with LN and control treatments (P > 0.05) after adjustment for pretreatment values, treatment period, and treatment order. Similarly, no differences were observed between treatments for arterial stiffness measures (P > 0.05). Conclusion: Increased intake of nitrate-rich vegetables did not lower blood pressure in prehypertensive or untreated grade 1 hypertensive individuals when comparedwith increased intake of nitrate-poor vegetables and no increase in vegetables. This trial was registered at www.anzctr.org.au as ACTRN12615000194561. [ABSTRACT FROM AUTHOR]

Background: Growth patterns of breastfed and formula-fed infants may differ, with formula-fed infants growing more rapidly than breastfed infants into childhood and adulthood. Objectives: Our objectives were to identify growth patterns and investigate early nutritional programming potential on growth patterns at 6 y and on body composition at 20 y. Design: The West Australian Pregnancy Cohort (Raine) Study and 3 European cohort studies (European Childhood Obesity Trial, Norwegian Human Milk Study, and Prevention of Coeliac Disease) that collaborate in the European Union-funded Early Nutrition project combined, harmonized, and pooled data on full breastfeeding, anthropometry, and body composition. Latent growth mixture modeling was applied to identify growth patterns among the 6708 individual growth trajectories. The association of full breastfeeding for <3 mo compared with ≥3 mo with the identified trajectory classes was assessed by logistic regression. Differences in body composition at 20 y among the identified trajectory classes were tested by analysis of variance. Results: Three body mass index (BMI; in kg/m2) trajectory patterns were identified and labeled as follows-class 1: persistent, accelerating, rapid growth (5%); class 2: early, nonpersistent, rapid growth (40%); and class 3: normative growth (55%). A shorter duration of full breastfeeding for <3 mo was associated with being in rapid-growth class 1 (OR: 2.66; 95% CI: 1.48, 4.79) and class 2 (OR: 1.96; 95% CI: 1.51, 2.55) rather than the normative-growth class 3 after adjustment for covariates. Both rapid-growth classes showed significant associations with body composition at 20 y (P < 0.0001). Conclusions: Full breastfeeding for <3 mo compared with ≥3 mo may be associated with rapid growth in early childhood and body composition in young adulthood. Rapid-growth patterns in early childhood could be a mediating link between infant feeding and long-term obesity risk. [ABSTRACT FROM AUTHOR]

Background: Nitrate-rich vegetables lower blood pressure and improve endothelial function in humans. It is not known, however, whether increased consumption of nitrate-rich vegetables translates to a lower risk of atherosclerotic vascular disease (ASVD) mortality. Objective: The objective was to investigate the association of nitrate intake from vegetables with ASVD mortality. Design: A total of 1226 Australian women aged 70-85 y without prevalent ASVD and/or diabetes were recruited in 1998 and were studied for 15 y. We assessed demographic and ASVD risk factors at baseline (1998), and we used a validated food-frequency questionnaire to evaluate dietary intake. Nitrate intake from vegetables was calculated by use of a newly developed comprehensive database. The primary outcome was any death attributed to ASVD ascertained by using linked data that were provided via the Western Australian Data Linkage system. We used Cox proportional hazards modeling to examine the association between nitrate intake and ASVD mortality before and after adjustment for lifestyle and cardiovascular disease risk factors. Results: During a follow-up period of 15,947 person-years, 238 of 1226 (19.4%) women died of ASVD-related causes. The mean 6 SD vegetable nitrate intake was 67.0 6 29.2 mg/d. Each SD higher vegetable nitrate intake was associated with a lower risk of ASVD mortality in both unadjusted [HR: 0.80 (95% CI: 0.70, 0.92), P = 0.002] and multivariable-adjusted [HR: 0.79 (95% CI: 0.68, 0.93), P = 0.004] analyses. This relation was attenuated after further adjustment for diet quality [HR: 0.85 (95% CI: 0.72, 1.01), P = 0.072]. Higher vegetable nitrate intake (per SD) also was associated with a lower risk of all-cause mortality [multivariableadjusted HR: 0.87 (95% CI: 0.78, 0.97), P = 0.011]. Conclusions: Nitrate intake from vegetables was inversely associated with ASVD mortality independent of lifestyle and cardiovascular disease risk factors in this population of older adult women without prevalent ASVD or diabetes. These results support the concept that nitrate-rich vegetables may reduce the risk of age-related ASVD mortality. This trial was registered at www. anzctr.org.au as ACTRN12617000640303. [ABSTRACT FROM AUTHOR]

Summary Background and objective The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD. Methods In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q 10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatography–tandem mass spectrometry before and after intervention. Results Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased ( P < 0.0001 ) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the E- and D-series resolvins, respectively. RvD1 was significantly increased ( P = 0.036 ) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively. Conclusion SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD. [ABSTRACT FROM AUTHOR]

Abstract: All types of aerobic exercise are assumed to affect cardiovascular risk similarly. There are few studies of swimming, but complex responses to water-based exercise suggest its potential for differential effects. The aim of the study was to compare the effects of swimming and walking on fitness, body weight, lipids, glucose, and insulin in older women. Sedentary women aged 50 to 70 years (N = 116), randomly assigned to swimming or walking plus usual care or a behavioral intervention, completed 3 sessions per week of moderate-intensity exercise, supervised for 6 months then unsupervised for 6 months. After 6 months, 1.6-km walk time decreased in walkers and swimmers, with greater improvement in walkers (1.0 vs 0.6 minute, P = .001). In swimmers, but not walkers, distance swum in 12 minutes increased (78.1 vs −2.2 m, P = .021). Waist and hip circumferences (80.8 vs 83.1 cm and 101.8 vs 102.4 cm; P = .023 and P = .042, respectively) and insulin area under the curve (oral glucose tolerance test) (5128 vs 5623 μU/[L 120 min], P < .05) were lower with swimming. Lipids did not differ between groups. At 12 months, fitness was maintained. Relative to walking, swimming reduced body weight by (1.1 kg, P = .039) and resulted in lower total and low-density lipoprotein cholesterol (0.3 and 0.2 mmol/L; P = .040 and P = .049, respectively). The magnitude of the difference in the reduction of insulin area under the curve between swimming and walking was greater at 12 months; however, the significance was attenuated (4677 vs 5240 μU/[L 120 min], P = .052). Compared with walking, swimming improved body weight, body fat distribution, and insulin in the short term and, in the longer term, body weight and lipid measures. These findings suggest that the type of exercise can influence health benefits. [ABSTRACT FROM AUTHOR]

Red meat intake has been associated with increased risk of coronary heart disease and type 2 diabetes, but it remains uncertain whether these associations are causally related to unprocessed lean red meat. It has been proposed that iron derived from red meat may increase iron stores and initiate oxidative damage and inflammation. We aimed to determine whether an increase in unprocessed lean red meat intake, partially replacing carbohydrate-rich foods, adversely influences markers of oxidative stress and inflammation. Sixty participants completed an 8-wk parallel-designed study. They were randomized to maintain their usual diet (control) or to partially replace energy from carbohydrate-rich foods with approximately 200 g/d of lean red meat (red meat) in isoenergetic diets. Markers of oxidative stress and inflammation were measured at baseline and at the end of intervention. Results are presented as the mean between-group difference in change and [95% CI]. Red meat, relative to control, resulted in: higher protein [5.3 (3.7, 6.9) % of energy], lower carbohydrate [-5.3 (-7.9, -2.7)% of energy], and higher iron [3.2 (1.1, 5.4) mg/d] intakes; lower urinary F2-isoprostane excretion [-137 (-264, -9) pmol/mmol creatinine], lower leukocyte [-0.51 (-0.99, -0.02)x10(9)/L] counts, and a trend for lower serum C-reactive protein concentrations [-1.6 (-3.3, 0.0) mg/L, P=0.06]; and no differences in concentrations of plasma F2-isoprostanes [-12 (-122, 100) pmol/L], serum gamma-glytamyltransferase [-0.8 (-3.2, 1.5) U/L], serum amyloid A protein [-1.4 (-3.4, 0.5) mg/L], and plasma fibrinogen concentrations [-0.08 (-0.40. 0.24) g/L]. Our results suggest that partial replacement of dietary carbohydrate with protein from lean red meat does not elevate oxidative stress or inflammation. [ABSTRACT FROM AUTHOR]

Red meat intake has been associated with increased risk of coronary heart disease and type 2 diabetes, but it remains uncertain whether these associations are causally related to unprocessed lean red meat. It has been proposed that iron derived from red meat may increase iron stores and initiate oxidative damage and inflammation. We aimed to determine whether an increase in unprocessed lean red meat intake, partially replacing carbohydrate-rich foods, adversely influences markers of oxidative stress and inflammation. Sixty participants completed an 8-wk parallel-designed study. They were randomized to maintain their usual diet (control) or to partially replace energy from carbohydrate-rich foods with -200 g/d of lean red meat (red meat) in isoenergetic diets. Markers of oxidative stress and inflammation were measured at baseline and at the end of intervention. Results are presented as the mean between-group difference in change and [95% CI]. Red meat, relative to control, resulted in: higher protein 15.3 (3.7, 6.9) % of energy], lower carbohydrate 1-5.3 1-7.9, -2.7) % of energy], and higher iron 13.2 11.1, 5.41 mg/dl intakes; lower urinary F2-isoprostane excretion 1-137 (-264, -9) pmol/mmol creatinine], lower leukocyte (-0.51 (-0.99, -0.021 × 109/L) counts, and a trend for lower serum C-reactive protein concentrations [-1.6 (-3.3, 0.0) mg/L, P = 0.061; and no differences in concentrations of plasma F2-isoprostanes 1-12 1-122, 100) pmol/L], serum γ-glytamyltransferase 1-0.8 (-3.2, 1.5) U/L], serum amyloid A protein 1-1.4 (-3.4, 0.5) mg/L], and plasma fibrinogen concentrations [-0.08 1-0.40. 0.24) g/L]. Our results suggest that partial replacement of dietary carbohydrate with protein from lean red meat does not elevate oxidative stress or inflammation. [ABSTRACT FROM AUTHOR]

Background: Compared with carbohydrate intake, dietary intake of plant protein can lower blood pressure in humans, but the effects of animal protein intake on blood pressure have yet to be investigated. Objective: We aimed to determine whether partial substitution of carbohydrate intake with animal protein intake from lean red meat changes blood pressure and other markers of cardiovascular disease risk in hypertensive persons. Design: Hypertensive persons (n=60) were recruited to an 8-wk parallel-design study. The participants were randomly assigned either to maintain their usual diet (control group) or to partially replace energy intake from carbohydrate-rich foods with protein from lean red meat (protein group). Measurements were performed at baseline and at the end of the intervention. Results: Compared with the control group, the protein group had a significantly higher protein intake [x (95% CI) percent of energy: 5.3% (3.7%, 6.9%), P < 0.001] and a corresponding lower carbohydrate intake [-5.3% of energy (-7.9%, -2.7%), P < 0.001]. Body weight and intakes of fat, alcohol, and fiber were not significantly different between the groups. Compared with the control group, the clinic, 24-h, awake, and asleep systolic blood pressures were lower [-5.2 (-10.3, -0.1), -4.0 (-7.4, -0.6), -4.7 (-8.9, -0.5), and-4.7 (-10.3,-0.1)mmHg, respectively, P<0.05] and fasting plasma glucose concentrations were higher [0.33 mmol/L (0.09, 0.58 mmol/L), P = 0.008] in the protein group. These differences were independent of age, sex, and changes in weight, alcohol intake, or urinary sodium and potassium excretion. Diastolic blood pressure and heart rate, arterial compliance, blood lipids, and serum insulin were not significantly different between the groups. Conclusion: Within the context of other studies, these results suggest that modest substitution of carbohydrate-rich foods with protein-rich foods may lower blood pressure in hypertensive persons. [ABSTRACT FROM AUTHOR]

Background: Overweight and inactivity are associated with impaired glucose tolerance, reduced insulin sensitivity, and diabetes. Few controlled trials have assessed the independent and combined effects of energy restriction and exercise on the prevention of these conditions. Objective: The objective was to evaluate the independent and additive effects of 16 wk of energy restriction and exercise on glucose and insulin concentrations. Design: Sixty nonsmoking, overweight, sedentary men aged 20-50 y were randomly assigned to either maintain or restrict their energy intake (4186-6279 kJ/d). Within each of these arms, the subjects were further randomly assigned to either a light-intensity (control) or a vigorous-intensity exercise program for 30 min 3 times/wk. Results: Fifty-one subjects completed the study. Maximal oxygen uptake increased (≈24%; P < 0.001) with vigorous but not with light exercise. Significant weight loss was observed with energy restriction (x: 10.12 kg; 95% CI: 8.02, 12.22 kg; P < 0.001) but not with exercise. Vigorous exercise reduced fasting glucose and glucose and insulin areas under the curve (AUCs) by 13% (P = 0.01) and20%(P = 0.02), respectively. Exercise effects were independent of weight change. Energy restriction resulted in a 40% reduction in the insulin AUC (P = 0.01). Vigorous exercise and energy restriction were additive in reducing the insulin AUC. Conclusions: Energy restriction and vigorous exercise independently and additively reduce glucose and insulin concentrations in response to an oral-glucose-tolerance test. Both of these lifestyle interventions provide a potent strategy that should be an integral part of any program to reduce the risk of impaired glucose tolerance, insulin resistance, and diabetes in overweight and sedentary persons. [ABSTRACT FROM AUTHOR]

Tea is rich in polyphenols, which have activities consistent with blood pressure-lowering potential. The effects of long-term regular ingestion of tea on blood pressure remain uncertain. We investigated the relationships of tea intake and a biomarker of exposure to tea-derived polyphenols (4-O-methylgallic acid) with blood pressure in a cross-sectional study of 218 women > 70 y old. Clinic blood pressures were measured and tea intake was assessed using a 24-h dietary recall; 4-O-methylgallic acid was measured for the same period in a 24-h urine sample. Mean (95% CI) daily tea intake was 525 (475, 600) mL. Mean systolic and diastolic blood pressures were 138.1 (135.6, 140.6) and 73.5 (72.1, 74.9) mm Hg. Higher tea intake and higher 4-O-methylgallic acid excretion were associated with significantly lower systolic (P = 0.002 and P = 0.040, respectively) and diastolic (P = 0.027 and P < 0.001, respectively) blood pressures. A 250 mL/d (1 cup) increase in tea intake was associated with a 2.2 (0.8, 3.6) mm Hg lower systolic blood pressure and a 0.9 (0.1, 1.7) mm Hg lower diastolic blood pressure. The observed associations for both tea intake and 4-O-methylgallic acid are consistent with the hypothesis that long-term regular ingestion of tea may have a favorable effect on blood pressure in older women. [ABSTRACT FROM AUTHOR]

Background: Polyphenols can act as acceptors of methyl groups during the metabolism of methionine to homocysteine. This may result in elevations in plasma total homocysteine (tHcy) concentrations after ingestion of polyphenol-rich beverages such as tea. Objectives: Our major objective was to determine whether regular, moderate-to-high intakes of black tea alter tHcy concentrations. We also assessed the relation between the degree of O-methylation of tea-derived polyphenols and the change in tHcy with regular ingestion of tea. Design: Twenty-two subjects completed a randomized, controlled crossover study. Subjects consumed 1250 mL black tea/d (5 cups each containing 2 g tea leaves in 250 mL boiled water) and 1250 mL hot water/d for 4 wk each. Fasting tHcy concentrations and 24-h urinary excretion of 4-O-methylgallic acid (4OMGA, the major O-methylated metabolite of gallic acid) were measured at the end of each period. 4OMGA was used as a marker of overall O-methylation of tea-derived polyphenols. Results: Black tea did not significantly alter mean (± SEM) tHcy concentrations (9.9 ± 0.5 and 10.0 ± 0.5 μmol/L for the hot water and black tea periods, respectively). However, the increased excretion of 4OMGA as a consequence of black tea consumption was positively associated with the change in tHcy from the hot water period to the black tea period (r = 0.55, P = 0.008). Subjects in the bottom quartile of increase in 4OMGA excretion had a significant decrease in tHcy (-0.28 ± 0.10 μmol/L; P = 0.046), and those in the top quartile had a significant increase in tHcy (0.78 ± 0.16 μmol/L; P = 0.005). Conclusions: Overall, regular ingestion of black tea did not alter mean tHcy concentrations. However, individual differences in Omethylation of polyphenolic compounds may influence the ultimate effects of black tea on tHcy. [ABSTRACT FROM AUTHOR]

Background: Lipid abnormalities may contribute to the increased risk of atherosclerosis and coronary disease in visceral obesity. Fish oils lower plasma triacylglycerols, but the underlying mechanisms are not fully understood. Objective: We studied the effect of fish oils on the metabolism of apolipoprotein B-100 (apo B) and chylomicron remnants in obese men. Design: Twenty-four dyslipidemic, viscerally obese men were randomly assigned to receive either fish oil capsules (4 g/d, consisting of 45% eicosapentaenoic acid and 39% docosahexaenoic acid as ethyl esters) or matching placebo (corn oil, 4 g/d) for 6 wk. VLDL, intermediate-density lipoprotein (IDL), and LDL apo B kinetics were assessed by following apo B isotopic enrichment with the use of gas chromatography-mass spectrometry after an intravenous bolus injection of trideuterated leucine. Chylomicron remnant catabolism was measured with the use of an intravenous injection of a chylomicron remnant-like emulsion containing cholesteryl [13C]oleate, and isotopic enrichment of 13CO2 in breath was measured with isotope ratio mass spectrometry. Kinetic values were derived with multicompartmental models. Results: Fish oil supplementation significantly (P < 0.05) lowered plasma concentrations of triacylglycerols (-18%) and VLDL apo B (-20%) and the hepatic secretion of VLDL apo B (-29%) compared with placebo. The percentage of conversions of VLDL apo B to IDL apo B, VLDL apo B to LDL apo B, and IDL apo B to LDL apo B also increased significantly (P < 0.05): 71%, 93%, and 11%, respectively. Fish oils did not significantly alter the fractional catabolic rates of apo B in VLDL, IDL, or LDL or alter the catabolism of the chylomicron remnant-like emulsion. Conclusion: Fish oils effectively lower the plasma concentration of triacylglycerols, chiefly by decreasing VLDL apo B production but not by altering the catabolism of apo B-containing lipoprotein or chylomicron remnants. [ABSTRACT FROM AUTHOR]

Prospective studies suggest that tea may protect against cardiovascular disease. A potential mechanism for such an effect involves inhibition of lipid peroxidation by polyphenolic antioxidants derived from tea. Our objective was to determine whether regular ingestion of tea could inhibit in vivo lipid peroxidation. Two controlled intervention studies assessed the effects of regular ingestion of tea on lipid peroxidation determined by measurement of urinary F(2)-isoprostane excretion. Study 1: The effects of 1000 mL/d of green tea and black tea were compared with hot water containing caffeine in 13 subjects with elevated blood pressure using a randomized 3-period (7 d each) crossover design. Study 2: The effects of 1250 mL/d of black tea were compared with hot water in 22 subjects with mildly raised serum total cholesterol concentrations using a randomized 2-period (4 wk each) crossover design. F(2)-isoprostane excretion was not altered after regular ingestion of green tea (273 +/- 48 pmol/mmol creatinine) or black tea (274 +/- 39 pmol/mmol creatinine) in comparison with hot water (263 +/- 47 pmol/mmol creatinine; Study 1), or by regular ingestion of black tea (334 +/- 71 pmol/mmol creatinine) in comparison with hot water (355 +/- 75 pmol/mmol creatinine; Study 2). These results do not support the suggestion that polyphenolic antioxidants derived from tea inhibit in vivo lipid peroxidation. [ABSTRACT FROM AUTHOR]

Isoflavonoids are a class of flavonoids that are derived in the human diet mainly from soybean-based foods. The major dietary isoflavonoids, genistein and daidzein, have estrogen-like activity and are classed as phytoestrogens. Because estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the objective of this study was to determine if isoflavonoids could improve serum lipids in healthy subjects. Forty-six men and 13 postmenopausal women not receiving hormone replacement therapy completed a randomized, double-blind, placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one placebo tablet was taken daily with the evening meal. Subjects maintained their usual diet and physical activity, which were unchanged throughout the intervention. Measurement of isoflavonoids and their metabolites in 24-h urine samples provided an assessment of compliance and of isoflavonoid metabolism. Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein (a) were assessed at baseline and during the last week of intervention. After adjustment for baseline values, no significant differences in postintervention serum lipid and lipoprotein (a) concentrations between groups were identified. Further adjustment for age, gender and weight change did not alter the results. In addition, changes in urinary isoflavonoids were not significantly correlated with changes in serum lipids and lipoprotein (a). Therefore, this study does not support the hypothesis that isoflavonoid phytoestrogens can improve the serum lipids, at least in subjects with average serum cholesterol concentrations. [ABSTRACT FROM AUTHOR]

Although much of the attention on diet and hypertension has centered around the rule of specific nutrients such as sodium, potassium, and alcohol, it has become evident that certain complex dietary patterns have a blood pressure-lowering effect and may help protect against the development of hypertension. It remains to be seen whether these effects on blood pressure require complex but specific combinations of nutrients or, alternatively, are due to hitherto unrecognized single nutrients with antihypertensive properties. The issues are difficult to resolve because people eat foods, not single nutrients, and there is a high degree of association between different nutrients in foods and patterns of food intake, as well as potentially confounding effects of other factors associated with eating habits such as age, body fat distribution, physical activity, alcohol consumption, tobacco use, and psychosocial stress. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effects of incorporating fish with 40%- or 30%-fat diets and the differences in response to fish or fish oil ω3 fats. Men with high-normal blood pressure and elevated serum cholesterol were randomly allocated to one of seven diets for 12 wk. Fish or fish oil with a 40%-fat diet increased total cholesterol, HDL cholesterol, HDL2 cholesterol, and LDL cholesterol, and reduced triglycerides. The 30%-fat diet alone reduced cholesterol, LDL cholesterol, and HDL cholesterol, with triglycerides unchanged. Fish with the 30%-fat diet reduced cholesterol, LDL cholesterol, and triglycerides and increased HDL2 cholesterol. This study has shown that plasma lipids are affected similarly by fish or fish oil in men consuming a 40%-fat diet. Adverse effects of ω3 fats on total and LDL cholesterol are reversed by a 30%-fat diet, whereas one daily fish meal substantially lowers triglycerides and reverses the fall in HDL cholesterol that is usual with a low-fat diet. [ABSTRACT FROM AUTHOR]

Evidence that nutrients other than the major cations may influence blood pressure levels stems from studies of acculturated vegetarians and from randomized controlled dietary trials. Earlier studies of vegetarians focused on religious groups and on vegans, making it difficult to know whether their lower blood pressures were due to diet per se or to other aspects of lifestyle. Seventh-day Adventist vegetarians showed significantly less hypertension and lower blood pressures compared with Mormon omnivores, effects which were independent of differences in obesity and not due to altered sodium intake. Subsequently, controlled dietary intervention studies in healthy normotensive omnivores provided more direct evidence for a blood pressure-lowering effect of a lactoovovegetarian diet with reversible changes of 5-6 mm Hg systolic and 2-3 mm Hg diastolic occurring over 6-wk periods. Similar dietary effects in mild hypertensive subjects provides impetus for identifying the responsible nutrients. [ABSTRACT FROM AUTHOR]

Recently, a relatively small reduction in systolic blood pressure (~5 mm Hg) was estimated to substantially reduce the numbers of major coronary events. The blood pressure reduction is about the same as the difference seen between typical ovolactovegetarians and omnivores. This paper reviews the evidence for the blood pressure-lowering effects of a vegetarian diet on those with elevated blood pressure. It also reviews whether the effect on blood pressure of a vegetarian diet can be attributed either to elevation of the dietary P:S ratio or to fiber intake alone. [ABSTRACT FROM AUTHOR]

Relationships between blood pressure and dietary factors were investigated in 884 9-y-old Australian children. Data on usual diet were obtained from a food frequency questionnaire completed by parents The data were used to estimate daily energy intake and intakes of 14 nutrients considered to have some potential for influencing blood pressure. Systolic and diastolic blood pressure were tested for relationships with absolute intakes and calorie-adjusted intakes of each nutrient after adjustment for potential confounders. Diastolic pressure in boys was negatively related to energy intake and to calorie-adjusted fiber intake. Mean adjusted diastolic pressure in boys in the top fiber-intake quartile was 2.5 mm Hg lower than that in the bottom fiber-intake quartile. Systolic pressure in girls was negatively related to calorie-adjusted intakes of protein and cholesterol. There were no detectable relationships between blood pressure and calorie-adjusted intakes of fats, carbohydrates, sodium, potassium, calcium, or magnesium. [ABSTRACT FROM AUTHOR]

The effect of intervention with a lacto-ovo vegetarian diet on serum concentrations of cholesterol, triglyceride, total high-density lipoprotein cholesterol (HDL-C), HDL2C, HDL3-C, low-density lipoprotein cholesterol, apoprotein-B, apoprotein-HDL, and Lp(a) was studied in 19 men and 17 women. Most weekday meals were obtained from a single source and dietary records were completed to assess the changes in nutrient intakes. Blood was collected in the 6th wk of each dietary period. Because of strong correlations between many of the changes in nutrient intakes, principal component (factor) analysis was used followed by stepwise multiple regression analysis to identify associations between changes in diet and changes in lipid, lipoprotein or apoprotein levels. Three principal components accounted for 92.0% of the variation in lipid levels: factor 1 represented an increase in saturated fat, total fat, monounsaturated fat, cholesterol, and energy intake: factor 2 represented an increase in fiber and polyunsaturated fat, and decrease in protein intake; factor 3 an increase in total carbohydrate, complex carbohydrate, and energy intake. Where a change in a variable was significantly associated with change in diet, one factor appeared primarily responsible for the change; total cholesterol (factor 2, p = 0.034); triglyceride (factor 3, p = 0.005); apo-HDL (factor 1, p = 0.0 14); HDL2C (factor 2, p = 0.023), HDL3-C (factor 3, p = 0.0 15). A borderline significant association was seen for total HDL-C(factor 2, p = 0.055). [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) significantly increases the risk of coronary heart disease. Most individuals are unaware they have the condition. In the Western Australian Pregnancy Cohort (Raine) Study, 1 in 267 adolescents were found to have FH. Universal cholesterol screening in childhood may offer the best strategy for diagnosing FH. [ABSTRACT FROM AUTHOR]

Background Activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with higher levels of cardiovascular (CVD) risk factors in adults. This study aimed to assess the relation between measures of HPA axis activity under resting conditions and CVD risk factors in a general population of adolescents at 17 years. Methods A total of 1134 adolescents from the Western Australian Pregnancy Cohort (Raine) Study had phenotypic and socio-demographic data. The associations between HPA axis measures (plasma ACTH, total cortisol, calculated free cortisol, corticosteroid binding globulin (CBG), and salivary cortisol) and a range of cardiovascular risk factors were examined using multivariable linear regression models, with adjustment for gender, adiposity, birth weight, gestational age, and socio-behavioural factors. Results Plasma total cortisol was positively associated with systolic blood pressure (SBP) ( p = 0.011), total cholesterol, HDL-cholesterol, and triglycerides (all p < 0.001), and hs-CRP ( p = 0.047). Salivary cortisol was associated positively with HDL-C ( p = 0.033) and negatively with LDL-cholesterol ( p = 0.016); plasma calculated free cortisol was positively associated with triglycerides ( p = 0.006); plasma CBG was positively associated with total cholesterol and HDL-cholesterol (both p < 0.001), LDL-cholesterol ( p = 0.022), and hs-CRP ( p = 0.001). After correction for multiple comparisons, significant associations remained for total cortisol with total cholesterol, HDL-C, and triglycerides; for calculated free cortisol with triglycerides; and for CBG with HDL-C, total cholesterol, and hs-CRP. Plasma ACTH was not associated with any cardiovascular risk factor. There was no association between BMI and any measure of HPA axis activity. Conclusion In an adolescent population, HPA axis measures under resting conditions are associated with a range of CVD risk factors. Clarification of the mechanisms underlying these associations in adolescence would be an important step in understanding the evolution of adult CVD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. Methods: To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52±16years from Italy, U.S.A., Japan, and Australia, included in the ‘ABP-International’ registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. Results: During a median follow-up of 5.0years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and =0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04–1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05–1.25) or subjects who had an event within 5years after enrollment (hazard ratio, 1.23; 95% CI, 1.05–1.45) were excluded from analysis. Conclusions: At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR. [Copyright &y& Elsevier]

Background Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . Objective This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. Design In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Results Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 ( P <  0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive from DHA (all P <  0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone ( P  = 0.013) but not when given in combination with CoQ. Conclusion n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. [ABSTRACT FROM AUTHOR]

Abstract: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that regulates vascular function and sodium homeostasis. Studies showing an association between 20-HETE excretion, raised BMI, and oxidative stress suggest that 20-HETE may be important in the development of cardiovascular disease in the metabolic syndrome (MetS). We investigated whether 20-HETE and F2-isoprostanes (markers of oxidative stress) were altered in the MetS before and after weight reduction. A case-controlled comparison of 30 participants with the MetS and matched controls showed that plasma and urinary 20-HETE and F2-isoprostanes were significantly elevated in the MetS group. There was a significant gender×group interaction such that women with the MetS had higher urinary 20-HETE and F2-isoprostanes compared to controls (p <0.0001). In a randomized controlled trial, 42 participants with the MetS were assigned to 16 weeks of weight maintenance or a 12-week weight-loss program followed by 4 weeks weight stabilization. Relative to the weight-maintenance group, a 4-kg loss in weight resulted in a 2-mm Hg fall in blood pressure (BP) but did not alter urinary or plasma 20-HETE or F2-isoprostanes. 20-HETE and oxidative stress may be important mediators of cardiovascular disease risk in the MetS. Although a 4% reduction in body weight reduced BP, there were no changes in plasma or urinary 20-HETE or F2-isoprostanes. [Copyright &y& Elsevier]

Abstract: There is considerable evidence that chronic moderate-to-high alcohol consumption increases blood pressure. The mechanisms by which this occurs are not clear. Alcohol consumption can induce oxidative stress and cytochrome P450 (CYP450) isoforms that are associated with oxidative stress and may influence vascular tone. To study the role of such mechanisms we examined whether reducing alcohol intake in moderate-to-heavy drinkers (40–110 g/day) resulted in changes in urinary excretion of 20-HETE, a CYP450 metabolite of arachidonic acid, and plasma and urinary F2-isoprostanes as markers of lipid peroxidation. After a 4-week run-in period during which healthy men maintained their usual drinking pattern they were randomized to a two-way crossover intervention study. In each of the 4-week treatment periods subjects either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake. Plasma and urinary F2-isoprostanes and urinary 20-HETE were measured by gas chromatography mass spectrometry, and serum γ-glutamyl transpeptidase (γ-GT) was measured as a biomarker of alcohol consumption, at the end of each study period. Sixteen healthy men age 51.0±2.7 years and with a BMI of 26.4±0.61 kg/m2 completed the study. The reductions in alcohol intake (72.4±5.0 vs 7.9±1.6 g/day, p <0.001) and serum γ-GT (geometric mean 24.4 U/L (95% CI 19.7, 30.2) vs 18.6 U/L (95% CI 15.5, 22.2, p <0.01) were accompanied by a significant fall in blood pressure as well as urinary 20-HETE excretion (158±23 vs 109±19 pmol/mmol creatinine, p <0.001) and plasma F2-isoprostanes (3438±158 vs 2929±145 pmol/L, p =0.01). A substantial reduction in alcohol consumption in healthy men lowered plasma F2-isoprostanes and urinary 20-HETE. Increased oxidative stress and 20-HETE production may be linked, at least in part, to the pathogenesis of alcohol-related hypertension. [Copyright &y& Elsevier]

Abstract: Hypertension is often associated with insulin resistance or hyperinsulinemia. Metabolism of arachidonic acid by cytochrome P450 to the vasoconstrictor 20-HETE is thought to be involved in the pathogenesis of hypertension, but the relationship of 20-HETE with insulin resistance is not clearly understood. Obesity is a major determinant of insulin resistance, and we have previously demonstrated a positive relationship between BMI and 20-HETE in untreated hypertensive and normotensive individuals. The present analysis sought to determine if this relationship was related to insulin levels or insulin resistance (HOMA). We analysed 24h urinary excretion of 20-HETE, serum insulin levels and insulin resistance in 66 lean to overweight untreated hypertensive and normotensive individuals. There was a significant positive association between 20-HETE and BMI (p <0.001), and serum insulin and BMI (p =0.003). There were no associations between 20-HETE excretion and either serum insulin or insulin resistance, before or after adjustment for age, gender, BMI and BP, or when hypertensive and normotensive individuals were considered separately. The results of the present study suggest that the observed positive association between urinary 20-HETE excretion and BMI may not be related to circulating insulin levels or insulin resistance. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the effect of consuming a variety of foods enriched in long-chain n-3 fatty acids in low fish eaters. Design: Evaluation of reported dietary intakes in a 6-month, double-blind, randomized, controlled parallel design trial. Subjects/setting: Eighty-five men and women with overweight and mildly elevated triglyceride levels who have a low habitual intake of fish. Intervention: Subjects were randomized to consume foods either enriched in long-chain n-3 fats or control foods (not enriched). Subjects were asked to consume eight portions per day (equivalent to approximately 1 g/day long-chain n-3 fatty acid if randomized to the intervention). Main Outcome Measure: Reported energy, macronutrient, and fatty acid intakes were measured by diet history, 3-day food records, and body weight. Statistical Analyses: Repeated measures analysis of variance, Kruskall-Wallis test, Pearson’s correlation coefficient, and Bland-Altman plots were conducted. Results: The two groups did not differ in mean dietary intake of long-chain n-3 fatty acid intake at baseline (258 mg and 313 mg for the intervention and control groups, respectively). At 6 months the intervention group members increased their intake of long-chain n-3 fats 4.5-fold compared with baseline and with the control group (P<.001). The data from the diet histories correlated well with the food records for all reported macronutrient and fatty acid values. Food pattern analysis showed that milk (13.8%), cereal (12.1%), and bread (11.3%) contributed the most to the overall long-chain n-3 fatty acid intake in the intervention group. Conclusions: This long-term study in free-living subjects indicates that population intakes of long-chain n-3 fatty acids could be substantially increased through the availability of a variety of n-3 fatty acid–enriched processed foods. [Copyright &y& Elsevier]

Abstract: Oxidative stress has been implicated in the pathogenesis of hypertension. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 product of arachidonic acid metabolism, thought to be involved in the regulation of blood pressure (BP). The metabolism of arachidonic acid by cytochrome P450 enzymes may be a significant source of oxidative stress. F2-isoprostanes are reliable markers of in vivo oxidative damage. γ-Glutamyl transpeptidase (γ-GT) has traditionally been associated with alcohol intake or liver dysfunction and may be an early marker of oxidative stress. The objective of the present study was to investigate relationships between 20-HETE excretion and markers of oxidative stress (F2-isoprostanes and γ-GT). Sixty-nine treated hypertensive subjects underwent measurement of 24-h ambulatory BP, serum γ-GT, and urinary F2-isoprostane and 20-HETE excretion. 20-HETE excretion was positively associated with 24-h diastolic BP (p = 0.005), alcohol intake (p = 0.008), γ-GT (p = 0.007), and F2-isoprostanes (p = 0.005). F2-isoprostanes were positively associated with alcohol intake (p = 0.018) and γ-GT (p = 0.01). In a multivariate regression, γ-GT remained an independent predictor of 20-HETE excretion, after adjustment for age, gender, BMI, and alcohol intake. In conclusion, the study highlights the positive association observed between 20-HETE excretion and markers of oxidative damage. The study also provides evidence that γ-GT may be a useful marker of oxidative stress. [Copyright &y& Elsevier]

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension. Our aim was to measure markers of oxidative stress in hypertensive subjects, and assess the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, lifestyle, and nutrition. Markers of oxidative stress, including plasma and 24 h urinary F2-isoprostanes, were measured in 70 untreated (men = 43, women = 27) and 85 treated (men = 43, women = 42) hypertensive subjects and 40 normotensive controls (men = 20, women = 20). Overall, F2-isoprostanes were not elevated in hypertensive subjects compared with controls. However, urinary and plasma F2-isoprostanes were significantly lower in treated compared with untreated hypertensive men, but not women. In hypertensive men, the number of antihypertensive drugs taken was inversely associated with both urinary and plasma F2-isoprostanes (p < .05). Self-reported alcohol intake and biomarkers of alcohol consumption (γ-glutamyl transpeptidase and high-density lipoprotein cholesterol) were positively associated with plasma but not urinary, F2-isoprostanes in men. Several nutrients were independently associated with plasma and urinary F2-isoprostanes in women. The results do not support the hypothesis that treated or untreated hypertensive subjects are under increased oxidative stress compared with normotensive controls. [Copyright &y& Elsevier]

n-3 Fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms. Despite this, there has been concern that these fatty acids may increase lipid peroxidation. The data in vivo are inconclusive, due in part to limitations in the methodologies. In this regard, the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress. This study aimed to assess the effects of supplementation with purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), the two major n-3 fatty acids, on urinary F2-isoprostanes and markers of inflammation, in type 2 diabetic patients. In a double-blind, placebo controlled trial of parallel design, 59 nonsmoking, treated-hypertensive, type 2 diabetic subjects, were randomized to 4 g daily of purified EPA, DHA, or olive oil for 6 weeks, while maintaining their usual diet. F2-isoprostanes, measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were measured before and after intervention. Thirty-nine men and 12 women aged 61.2 ± 1.2 years, with body mass index (BMI), 29.5 ± 0.5 kg/m2; 24 h blood pressure, 138/73 mmHg; HbA1c, 7.3 ± 0.1% and fasting glucose, 7.9 ± 0.2 mmol/l completed the intervention. Baseline urinary F2-isoprostanes were positively associated with HbA1c (p = .011) and fasting glucose (p = .032). Relative to the olive oil group, postintervention urinary F2-isoprostanes were decreased 19% by EPA (p = .017) and 20% by DHA (p = .014). There were no significant changes in CRP, IL-6, and TNF-α following EPA or DHA supplementation. In regression analysis, Δ F2-isoprostanes were positively associated with Δ HbA1c (p = .007) independent of treatment group; and with Δ TNF-α (p = .034) independent of age, gender, BMI, and treatment group. There were no associations with Δ CRP or Δ IL-6. This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation, in treated hypertensive, type 2 diabetic subjects. [Copyright &y& Elsevier]

Background: Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis. We assessed whether purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil have differential effects on platelet, fibrinolytic and vascular function in patients with both conditions. Methods: In a double-blind placebo-controlled trial of parallel design, 59 treated-hypertensive Type 2 diabetic men and postmenopausal women, were randomised to 4 g/day of EPA, DHA or olive oil (placebo) for 6 weeks. Collagen and PAF-stimulated platelet aggregation, collagen-stimulated thromboxane release (TXB2), plasma tPA and PAI-1 antigens, von Willebrand factor, p-selectin, and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery, were examined before and at the end of intervention. Results: Thirty-nine men and 12 women aged 61.2±1.2 year completed the study. Relative to placebo, DHA but not EPA supplementation significantly reduced collagen aggregation (16.9%, P=0.05) and TXB2 (18.8%, P=0.03). There were no significant changes in either PAF-stimulated platelet aggregation, fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo. Conclusion: Highly purified DHA may be a more effective anti-thrombotic agent than EPA. However, longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension. [Copyright &y& Elsevier]

Background: Traditional cardiovascular risk factors may only partially explain abnormal vascular function in Type 2 diabetic patients. This study examined the associations between vascular function and markers of inflammation in Type 2 diabetic subjects with treated hypertension. Methods: Flow-mediated dilatation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) of the brachial artery were used to assess endothelium-dependent and -independent function, respectively, in 29 hypertensive Type 2 diabetic subjects (HbA1c <9%), and 17 healthy control subjects. Plasma C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leukocyte count were used as markers of inflammation. Soluble L-selectin, P-selectin, and von Willebrand factor (vWf) were measured to assess leukocyte, platelet and endothelial cell activation, respectively. Results: Compared with controls, diabetic subjects had impaired FMD (3.9±3.0 vs. 5.5±2.4%, P=0.07) and GTNMD (11.4±4.8% vs. 15.4±7.1%, P=0.04). They also had higher levels of CRP (2.7±2.6 vs. 1.4±1.1 mg/l, P=0.03), fibrinogen (3.4±0.7 vs. 2.7±0.3 g/l, P<0.001) and TNF-α (20.9±13.4 vs. 2.5±1.7 pg/l, P<0.001). In diabetic subjects, after adjustment for age and gender, leukocyte count was an independent predictor of FMD (P=0.02), accounting for 17% of total variance. Similarly, leukocyte count (P<0.001) accounted for 23% and IL-6 (P=0.03) for 12% of the variance in GTNMD. vWf was correlated with leukocyte count (r=0.38, P=0.04), FMD (r=−0.35, P=0.06) and GTNMD (r=−0.47, P=0.009), whilst P-selectin correlated with fibrinogen (r=0.58, P=0.001). Conclusion: These cross-sectional observations are consistent with the hypothesis that reduced FMD and GTNMD in Type 2 diabetes is at least in part secondary to increased inflammation, with associated endothelial and platelet activation. [Copyright &y& Elsevier]