Maternal fatty acid status in pregnancy and childhood atopic manifestations: KOALA Birth Cohort Study.

BACKGROUND: Prevalence of atopic disorders has increased rapidly, but aetiological factors responsible for this increase are still largely unknown. Prenatal exposure to a pro-inflammatory fatty acid status is hypothesized although little research has been carried out. OBJECTIVE: To investigate whether prenatal fatty acid exposures are associated with atopy in childhood. METHODS: In the KOALA Birth Cohort Study, maternal blood samples (n=1275) at 34-36 weeks of pregnancy were assayed for n-6 and n-3 long-chain polyunsaturated fatty acids (LCPs). The full spectrum of offspring atopic manifestations (wheeze, asthma, allergic rhinoconjunctivitis, eczema, atopic dermatitis, allergic sensitization, and high total IgE) until the age of 6-7 years was assessed by repeated parental questionnaires and measurements of total and specific IgE. Associations of maternal fatty acid status with child atopic outcomes were analysed using multivariable logistic regression and generalized estimating equations for repeated measurements. RESULTS: High ratio of maternal n-6 vs. n-3 LCPs was associated with a lower risk of eczema in the child (P for trend 0.012). More specifically, we found a decreased risk of eczema in the first 7 months of life with increasing arachidonic acid levels (P for trend 0.013). No associations were found between maternal fatty acids and offspring airway-related atopic manifestations, sensitization, or high total IgE. CONCLUSION AND CLINICAL RELEVANCE: The development of atopic disorders in early childhood is associated with prenatal exposure to n-6 vs. n-3 fatty acids, but with inconsistencies between different manifestations. Further exploration of associations with maternal diet and genetic variants in genes regulating fatty acid metabolism are required. This study shows that the influence of prenatal exposure to fatty acids on the risk of eczema in the child is limited to the first year of life.

Serum micronutrient concentrations and childhood asthma: the PIAMA birth cohort study.

BACKGROUND: Research suggests an influence of micronutrients on childhood asthma. So far, evidence mainly originates from cross-sectional studies using nutrient intake data, which is not an accurate measure of nutrient status. This study aimed to investigate the cross-sectional and prospective associations between serum concentrations of magnesium, vitamin D, selenium, and zinc and prevalence of (severe) asthma, atopy, and bronchial hyperresponsiveness (BHR) in childhood. METHODS: In the Prevention and Incidence of Asthma and Mite Allergy birth cohort study, serum nutrient concentrations were available for a 4-yr-old subgroup (n = 372) and for a different 8-yr-old subgroup (n = 328). Yearly questionnaires inquired about asthma prevalence until 8 yr of age. Allergic sensitization was measured at 4 and 8 yr of age; BHR was measured at 8 yr of age. Data were analyzed with logistic regression and generalized estimating equations models. RESULTS: There was a consistent (non-significant) inverse association between serum magnesium concentrations and asthma prevalence. Serum vitamin D concentrations measured at age 4 were inversely associated with asthma at ages 4-8 [e.g., cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma: odds ratio (OR): 0.49, 95% confidence interval (CI): 0.25-0.95], whereas vitamin D measured at age 8 was positively associated with asthma at age 8 (e.g., cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma: OR: 2.14, 95% CI: 0.67-6.82). CONCLUSIONS: Our study contributes to the evidence that children with higher serum magnesium concentrations are less likely to have asthma. The associations between serum vitamin D concentrations and asthma were age-dependent.

Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Vitamin E supplementation during the dry period in dairy cattle. Part I: adverse effect on incidence of mastitis postpartum in a double-blind randomized field trial.

A randomized, controlled field trial with dairy cows demonstrated an adverse effect of vitamin E supplementation during the dry period on mastitis incidence in early lactation. This study was conducted on farms with historically high rates of mastitis to investigate the benefit of vitamin E supplementation on udder health; however, the outcome showed an adverse effect. The aim of the study was to evaluate whether daily supplementation of 3,000 IU of vitamin E to dairy cows during the dry period could improve udder health in commercial herds with a high incidence of mastitis. On 5 dairy farms, dry cows were randomly divided into 2 experimental groups: a high and a low group. Both groups received a dry cow mineral mix providing 3,000 or 135 IU of vitamin E/cow per day, respectively, between dry-off and calving for a mean period of 8 wk. Providing 3,000 IU of vitamin E exceeds NRC standards, but this amount has been used in previous studies. The experiment, as well as the majority of the statistical analysis, were carried out blinded. Blood was sampled 3 times before calving and on calving day. Serum was analyzed for vitamin E and cholesterol. Vitamin E and the vitamin E:cholesterol ratio were analyzed as dependent variables in mixed models and Student's t-tests to study trends in time and differences between groups. Relative risk calculation and survival analysis were used to study the effect of supplementation on mastitis incidence in the first 3 mo of lactation. The results showed that vitamin E supplements increased both absolute vitamin E and the ratio of vitamin E to cholesterol in blood. In the high group, significantly more subclinical and clinical cases occurred, showing the same trend on all farms. In this study, an initial vitamin E level at dry off above 14.5 µmol/L was a risk factor for clinical mastitis, suggesting that the vitamin E status at the start of the dry period is important. It is recommended to work out exactly at what threshold vitamin E is harmful for udder health before new trials with high dosages of vitamin E are started. Additionally, further research is required to investigate the mechanism by which vitamin E affects udder health.

Vitamin E supplementation during the dry period in dairy cattle. Part II: oxidative stress following vitamin E supplementation may increase clinical mastitis incidence postpartum.

The aim of this study was to evaluate, retrospectively, which physiological states influenced the effect of vitamin E supplements during the dry period on the level of oxidative stress at 2 wk antepartum. Furthermore the effect of oxidative stress at 2 wk antepartum on the risk of clinical mastitis in early lactation was investigated. Cows experience oxidative stress around calving. Vitamin E is able to decrease oxidative stress by scavenging free radicals. Normally, vitamin E radicals formed when vitamin E reacts with free radicals are regenerated by a network of other antioxidants, termed the "vitamin E regeneration system" (VERS). In case of vitamin E supplementation, VERS should be sufficient to regenerate formed vitamin E radicals; if not, oxidative stress might increase instead of decrease. Additionally, the level of oxidative stress and vitamin E might be important physiological states to evaluate before supplementation. In a clinical trial, 296 cows on 5 farms were randomly divided into 2 groups, supplemented with a mineral mix between dry off and calving that supplied 3,000 or 135 IU/d, respectively. Blood samples collected at dry off and 2 wk antepartum were analyzed for vitamin E, reactive oxygen metabolites, ferric-reducing ability of plasma, glutathione peroxidase, and malondialdehyde. Cows were allocated retrospectively into 8 subgroups based on the level of oxidative stress, vitamin E, and VERS status at dry off. To evaluate whether differences in physiological states at dry off influenced the effect of vitamin E supplementation on the level of oxidative stress, group effects (supplemented vs. control) were studied with Student's t-test for all 8 subgroup at 2 wk antepartum. Differences in physiological states at dry off influenced the effect of vitamin E supplements. In 2 insufficient VERS subgroups, the supplemented group had higher levels of free radicals at 2 wk antepartum compared with the control group. Relative risk calculation was used to study the effect of oxidative stress at 2 wk antepartum on the incidence of mastitis in the first 100 d of lactation. Higher levels of oxidative stress at 2 wk antepartum were related to higher risk of clinical mastitis. In conclusion, not every dry cow responded well to high vitamin E supplementation. This subgroup analysis provides a possible explanation for the unexpected adverse effects observed in the clinical trial.

Effects of vitamin E supplementation on and the association of body condition score with changes in peroxidative biomarkers and antioxidants around calving in dairy heifers.

The objective of this study was to investigate the effect of vitamin E supplementation on oxidative status in blood, liver, milk, and ovarian follicular fluid in periparturient heifers. Vitamin E supplementation started 8 wk before calving and continued until 8 wk postpartum. Grass silage was the main forage fed during the experiment. In addition, supplemented heifers (n=9) received 3,000I U of vitamin E daily on a carrier food; control heifers (n=9) consumed only the carrier food. Blood samples and liver biopsies were taken frequently throughout the study and ovarian follicular fluid was sampled at 8 wk postpartum. Body condition score was scored weekly and milk yield was measured daily. A marker of oxidative damage, determinable reactive oxygen metabolites (d-ROM), and a set of antioxidants were measured in blood, liver, milk, and ovarian follicular fluid. Control heifers had a low vitamin E status, and selenium status was marginal in control and supplemented heifers. Vitamin E supplementation increased vitamin E concentrations in blood, liver, and ovarian follicular fluid and increased triacylglycerol in liver. Serum d-ROM were not reduced by vitamin E supplementation. Superoxide dismutase and glutathione peroxidase activity in red blood cells and liver and glutathione peroxidase activity in ovarian follicular fluid were not affected by vitamin E supplementation and they were not increased around calving. Protein thiol groups and ratio of reduced glutathione to oxidized glutathione were also not increased around calving. These results suggest that heifers around calving experience a low level of oxidative processes. This might be caused by lower than expected milk production attributed to a low forage intake. Serum d-ROM were negatively correlated with protein thiol groups and positively correlated with the activity of glutathione peroxidase in red blood cells, oxidized glutathione, and the ratio of reduced glutathione and oxidized glutathione in serum. The lack of treatment effects allowed estimation of the effects of body condition 4 wk before calving and the loss of body condition on markers of lipid peroxidation and antioxidants. A trend that a body condition of >or=3 might result in more oxidative damage measured by serum d-ROM was observed, but fatter heifers had a significantly higher ratio of reduced glutathione to oxidized glutathione.

Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study.

BACKGROUND: Low-grade inflammation has been hypothesized to underlie the coronary artery disease (CAD) risk associated with the metabolic syndrome, but the evidence is not conclusive. For peripheral arterial disease (PAD; as measured by the ankle-arm index), this association has not been studied before. The aim was to study whether the association between the metabolic syndrome and CAD or the severity of PAD can be explained by low-grade inflammation. METHODS: The Cohort study Diabetes and Atherosclerosis Maastricht population includes 574 subjects, with an increased risk of type 2 diabetes, of whom 560 were included in the analyses (343 males; age: 59.5 +/- 7.0 years). The inflammation markers that were measured were C-reactive protein, interleukin 6, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and serum amyloid A. All analyses were adjusted for age, sex and smoking. RESULTS: Logistic regression showed that the metabolic syndrome was significantly associated with CAD [odds ratio (OR) = 1.86, 95% CI: 1.21; 2.84, P = 0.004]. Further adjustment for inflammatory status, as captured in a combination of the inflammation markers (using an averaged Z-score), resulted in significant associations of both the metabolic syndrome and inflammatory status with CAD [OR(metabolic syndrome) (95% CI) = 1.58 (1.01; 2.46), P = 0.044; OR(inflammation) (95% CI) = 1.59 (1.14; 2.21), P = 0.007]. Linear regression analysis showed similar results for the ankle-arm index. CONCLUSIONS: The association between the metabolic syndrome, on the one hand, and prevalence of CAD or the severity of PAD, on the other, can be partly but not completely, 26% and 29% respectively, explained by low-grade inflammation.

Changes in transferrin are related to changes in insulin resistance: the SLIM study.

AIMS: To determine the effect of a lifestyle intervention on serum transferrin and ferritin levels and the relationship between changes in transferrin and ferritin and changes in glucose tolerance and insulin resistance. METHODS: Randomized controlled lifestyle intervention directed at a healthy diet and increased physical activity in subjects with impaired glucose tolerance. RESULTS: After 1 year, the change in ferritin levels in the intervention group as compared with the control group did not reach statistical significance (P = 0.06). Transferrin change was independently related to the change in homeostasis model assessment of insulin resistance and ferritin change was related to the change in 2-h free fatty acids. CONCLUSIONS: Changes in insulin sensitivity and postprandial lipid metabolism are related to changes in iron metabolism.

Short-term beta-adrenergic regulation of leptin, adiponectin and interleukin-6 secretion in vivo in lean and obese subjects.

AIM: Adipose tissue and skeletal muscle are endocrine organs, secreting substances that have been implicated in obesity-related disorders. This study examined short-term beta-adrenergic regulation of circulating leptin, adiponectin and interleukin-6 (IL-6) concentrations and secretion from abdominal subcutaneous adipose tissue and muscle (IL-6) in vivo in lean and obese subjects. METHODS: Systemic concentrations and net fluxes of leptin, adiponectin and IL-6 across abdominal subcutaneous adipose tissue and forearm skeletal muscle (IL-6) were assessed before and during beta-adrenergic stimulation (intravenous isoprenaline infusion) in 13 lean and 10 obese men. RESULTS: Basal circulating leptin concentrations were higher in the obese (p < 0.001), while circulating adiponectin (p = 0.45) and IL-6 concentrations (p = 0.41) were not different between groups. beta-Adrenergic stimulation decreased leptin concentrations in both groups (p < 0.01), but did not reduce net abdominal subcutaneous adipose tissue leptin release. Increased leptin clearance and/or decreased leptin secretion from other fat depots may explain the reduction in leptin concentrations. Adiponectin concentrations remained unchanged during beta-adrenergic stimulation in both groups. beta-Adrenergic stimulation increased IL-6 concentration, which was more pronounced in the obese (p = 0.01 vs. lean). This cannot be explained by increased IL-6 release per unit abdominal subcutaneous adipose tissue and muscle but might be because of the increased fat mass and fat-free mass at whole-body level. CONCLUSIONS: Short-term beta-adrenergic stimulation decreases leptin concentrations, which cannot be explained by reduced net leptin release from abdominal subcutaneous adipose tissue, while it elevates IL-6 concentration partly by increased release from this fat depot and muscle. Finally, beta-adrenergic stimulation has no short-term regulatory role in adiponectin secretion.

Effects of rosuvastatin on postprandial leukocytes in mildly hyperlipidemic patients with premature coronary sclerosis.

We investigated whether pro-inflammatory aspects of the postprandial phase can be modulated by rosuvastatin in premature coronary artery disease (CAD) patients. Herefore standardized 8 h oral fat loading tests were performed off-treatment and after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was studied using flowcytometry. Migration of isolated neutrophils towards chemoattractants was determined in a fluorescence-based assay. Rosuvastatin did not affect baseline leukocyte counts nor the postprandial neutrophil increment (maximum mean increase +10% pre- and +14% post-treatment, P < 0.01 for each). Rosuvastatin reduced baseline platelets (from 266 +/- 78 to 225 +/- 74 x 10(9) cells/L, P < 0.001) and blunted the postprandial platelet count change (maximum mean increase +6%, P = 0.01, and 0%, respectively). The baseline expression of CD11a, CD11b and CD62L increased on most types of leukocytes by rosuvastatin, whereas the postprandial responses were unaffected. Pretreatment, postprandial neutrophil migration increased dose-dependently, but there were no postprandial changes after rosuvastatin. The latter effect was unrelated to changes in lipoprotein concentrations. In conclusion, in CAD patients postprandial pro-inflammatory and pro-coagulant changes can be modified by rosuvastatin. These apparently lipid-lowering independent effects may render protection against atherosclerosis.

Polymorphism Ncol in tumor necrosis factor B is associated with fasting glycemia and lipid parameters in healthy non-obese caucasian subjects.

BACKGROUND: The study was designed to investigate the associations among polymorphisms TNF-B Ncol and TNF-alpha -308G/A, plasma TNF-alpha levels and metabolic and anthropometric parameters related to insulin sensitivity in a set of 113 Caucasian subjects undergoing oral glucose tolerance test (oGTT). METHODS: Genotypes were detected by PCR; BMI, WHR, glycemia during oGTT, fasting immunoreactive insulin, fasting C-peptide, HbA(1c), total cholesterol, triglycerides, HDL, LDL and plasma TNF-alpha levels were measured in each subject. RESULTS: Type 2 diabetes was diagnosed in 10 subjects, impaired glucose tolerance (IGT) in 41, normal glucose tolerance (NGT) in 62. Significant differences among genotypes of the TNF-B Ncol were observed for FPG (P=0.0063), LDL (P=0.0179) and marginally for total cholesterol (P=0.0763) in NGT group. After the classification of NGT subjects into obese and non-obese according to BMI, associations of TNF-B Ncol with FPG, LDL and cholesterol were proved in non-obese subgroup only. TNF-alpha -308G/A polymorphism was not associated with any of the parameters studied. TNF-alpha levels did not revealed difference among NGT, IGT and DM groups or genotype-dependent differences. CONCLUSIONS: Our results indicate significant association of the TNF-B Ncol polymorphism with FPG, LDL and total cholesterol in normoglycemic non-obese Caucasian subjects. This polymorphism could be involved in genetic modulation of glucose and lipid homeostasis and regulation of insulin sensitivity already in healthy state. Disturbances of this regulation could be component of pathogenesis of type 2 diabetes mellitus.

Relations among serum ferritin, C282Y and H63D mutations in the HFE gene and type 2 diabetes mellitus in the Czech population.

Aims of the study were: (i) to determine the prevalence of mutations C282Y and H63D in the HFE gene causing hereditary hemochromatosis in patients with type 2 diabetes mellitus and non-diabetics, (ii) to investigate the relationship among HFE genotypes, serum ferritin and glucose intolerance and (iii) to assess possible association of HFE mutations with the susceptibility to develop late diabetic complications in the Czech population. Two approaches were employed - the case-control study comprising diabetics and non-diabetic controls (n = 326) and the cross-sectional study comprising subjects with a previously unknown defect of glucose tolerance (n = 113, oral glucose tolerance test performed in each subject). Allele frequencies of C282Y and H63D did not differ between diabetic and control groups nor among subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes. Ferritin levels significantly differed between diabetic and non-diabetic women (P<1.10 (-3)) and among subjects with NGT, IGT and diabetes (P<0.05). Differences in ferritin levels related to particular genotypes of C282Y and H63D were not detected. Prevalence of diabetes in the first and second quartiles of ferritin distribution differed highly significantly from the prevalence in the third and fourth quartiles in women (P = 0.000037), OR = 3.50 (95% CI, 1.89-6.48). The extent of diabetic late complications did not correlate with ferritin plasma levels.

Long-term stability of parameters of antioxidant status in human serum.

The antioxidant status of serum or plasma can be determined using several commercially available assays. Here, four different assays, total antioxidant status (TAS), its second-generation assay (TAS2), biological antioxidant potential (BAP), and enzymatic assay using horseradish peroxidase (EAOC), were applied on human serum samples to test the temperature stability of antioxidants, upon storage of serum for 12 months. The two or three most commonly used temperatures for storage, that is, - 20, - 70 (or - 80), and - 196°C, were selected. The general conclusion is that all assays were stable at the temperatures tested. In addition, there were almost no statistically significant differences between the samples stored at different temperatures. Only the rank order of the EAOC assay was not very good in samples stored at - 20°C. Also three components contributing to the total antioxidant capacity, uric acid, creatinine and bilirubin, showed no statistically significant differences between the temperatures. Therefore, storage at - 20°C is sufficient to maintain a proper assay outcome of most of the total antioxidant assays, although storage at - 70/80°C is to be preferred for longer storage times.

Reproductive and lifestyle determinants of anti-Müllerian hormone in a large population-based study.

CONTEXT: Anti-müllerian hormone (AMH) is an ovarian reserve marker that is increasingly applied in clinical practice as a prognostic and diagnostic tool. Despite increased use of AMH in clinical practice, large-scale studies addressing the influence of possible determinants on AMH levels are scarce. OBJECTIVE: We aimed to address the role of reproductive and lifestyle determinants of AMH in a large population-based cohort of women. DESIGN: In this cross-sectional study, age-specific AMH percentiles were calculated using general linear modeling with CG-LMS (Cole and Green, Lambda, Mu, and Sigma model, an established method to calculate growth curves for children). SETTING: Women from the general community participating in the Doetinchem Cohort study were assessed. PARTICIPANTS: Two thousand three hundred twenty premenopausal women were included. MAIN OUTCOME MEASURE: The effect of female reproductive and lifestyle factors on shifts in age-specific AMH percentiles was studied. RESULTS: In comparison to women with a regular menstrual cycle, current oral contraceptive (OC) users, women with menstrual cycle irregularity, and pregnant women had significantly lower age-specific AMH percentiles (for OC use, 11 percentiles lower; for cycle irregularity, 11 percentiles lower; and for pregnancy, 17 percentiles lower [P value for all <.0001]). Age at menarche and age at first childbirth were not associated with the age-specific AMH percentile. Higher parity was associated with 2 percentiles higher age-specific AMH (P = .02). Of the lifestyle factors investigated, current smoking was associated with 4 percentiles lower age-specific AMH percentiles (P = .02), irrespective of the smoking dose. Body mass index, waist circumference, alcohol consumption, physical exercise, and socioeconomic status were not significantly associated with age-specific AMH percentiles. CONCLUSIONS: This study demonstrates that several reproductive and lifestyle factors are associated with age-specific AMH levels. The lower AMH levels associated with OC use and smoking seem reversible, as effects were confined to current use of OC or cigarettes. It is important to give careful consideration to the effect of such determinants when interpreting AMH in a clinical setting and basing patient management on AMH.

Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: a randomized, double-blind placebo-controlled study.

BACKGROUND: Depression is common in individuals with diabetes. The present study is the first randomized controlled trial to test the efficacy of omega-3 ethyl-eicosapentaenoic acid (E-EPA) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus. METHODS: In the VU University Medical Center, we conducted a 12-week, placebo-controlled, double-blind, parallel-group intervention study of E-EPA (1g/day) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder, who were already using antidepressant medication. The primary outcome was severity of depressive symptoms, assessed by the Montgomery Asberg Depression Rating Scale (MADRS) at baseline and 12-week follow-up at two-weekly intervals. Blood samples were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes. Data were analyzed with ANOVA for repeated measures. RESULTS: Thirteen participants were randomly assigned to E-EPA; 12 participants were given placebo. At 12-week follow-up, erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA, while no changes were noted in participants receiving placebo. In both groups, depressive symptoms significantly decreased over time (F=21.14, p<0.001), yet no significant differences were found between those treated with E-EPA versus placebo (F=1.63, p=0.17). LIMITATIONS: Although having sufficient study power, this study had a relatively small sample size. Small effects could not be detected, and dose-dependent effects could not be studied. CONCLUSIONS: No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression.

Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: the SLIM study.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether lifestyle intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes. MATERIALS AND METHODS: In the Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM), 97 men and women with IGT were randomised to a combined diet and exercise programme (47 intervention) or a control group (50 control subjects). At baseline and after 1 year the following assessments were made: an OGTT, an exercise test to determine maximal aerobic capacity, anthropometry, and analysis of the serum fatty acid profile of cholesteryl esters. RESULTS: The lifestyle programme was effective in reducing the intake of total and saturated fat, increasing physical activity, reducing obesity and improving insulin sensitivity and glucose tolerance. Regression analysis of the total population showed that an increase in the C20:4 n-6/C20:3 n-6 ratio (estimated Delta5-desaturase activity) and reductions in the C18:3 n-6/C18:2 n-6 ratio (estimated Delta6-desaturase activity) and the C16:1 n-7/C16:0 ratio (estimated Delta9-desaturase activity or stearoyl-CoA desaturase-1) were significantly associated with a decrease in homeostasis model assessment for insulin resistance. After adjustment for lifestyle changes (change in percentage body fat, aerobic capacity and saturated fat intake), these associations were partly reduced, but remained statistically significant. CONCLUSIONS/INTERPRETATION: Lifestyle-induced changes in fatty acid profile of cholesteryl esters and desaturase activities were independently related to changes in insulin sensitivity in subjects at risk of type 2 diabetes.

Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin D, C-reactive protein and fructosamine in two Dutch cohorts.

Biomarkers are widely used in epidemiology, yet there are few reliability studies to assess the appropriateness of using these biomarkers for the assessment of exposure-disease relationships. The aim of the study was to assess the reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht and Bilthoven) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total iron, total iron-binding capacity, transferrin saturation, transferrin, C-reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid, creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma, protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were analysed from the blood samples at the two points of time. For all biomarkers, except C-reactive protein, there were no substantial changes in the mean levels over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels consistently showed the highest reliability for men and women (intra-class correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and protein thiol oxidation had poor reliability; and among men iron-related biomarkers (except serum ferritin) had poor reliability. With the exception of a few gender-specific differences, most of the 20 biomarkers performed well and can be considered to have sufficient reliability to be used in future cohort studies.

Postprandial recruitment of neutrophils may contribute to endothelial dysfunction.

Atherosclerosis is a low-grade inflammatory disease involving leukocytes, lipids, and glucose leading to endothelial dysfunction. Since activation of neutrophils by triglycerides and glucose has been described in vitro, we hypothesized that the postprandial phase is an inflammatory state affecting leukocytes, possibly contributing to endothelial dysfunction. We measured postprandial blood leukocyte counts, cytokines, hydroperoxides (HPOs), and flow-mediated vasodilation (FMD) in eight healthy males (age 23 +/- 2 years) after a FAT (50 g/m2) and GLUCOSE challenge (37.5 g/m2), a combination of both (MIXED test), and after WATER. All tests, except WATER, resulted in significantly impaired FMD (10% reduction) between t = 1 h and t = 3 h, accompanied by a significant increase of neutrophils (59% after FAT and 28% after GLUCOSE and MIXED), total plasma HPOs (15 to 31% increase), and plasma interleukin-8 (IL-8) (50-130% increase). WATER did not affect FMD, neutrophils, HPOs, or IL-8. Lymphocytes increased gradually in all tests (40-70% increase at t = 10 h compared with t = 0; P < 0.005), paralleling a gradual 3- to 5-fold interleukin-6 increase. Monocyte and erythrocyte counts did not change in any test. In conclusion, the neutrophil increment during postprandial lipemia and glycemia with concomitant IL-8 and HPO increases may contribute to endothelial dysfunction. Lymphocyte increment is a nonspecific diurnal process. Postprandial intravascular inflammatory changes may be relevant for the pathogenesis of atherosclerosis.