Reduced circulating adiponectin levels are associated with the metabolic syndrome independently of obesity, lipid indices and serum insulin levels: A cross-sectional study

Background: Given the increasing rate of overweight and the burden of metabolic syndrome (MetS) on cardiovascular disease development, better understanding of the syndrome is of great importance. Therefore, the objectives were to examine whether interleukin-6 (IL-6) and adiponectin are associated with MetS, and whether this association is mediated by components of the MetS. Methods: During 2011-2012, 284 individuals (159 men, 53 ± 9 years, 125 women 52 ± 9 years) without cardiovascular disease, type 1 diabetes mellitus, high-grade inflammatory disease, living in the greater Athens area, Greece, participated in clinical examination. Adiponectin and IL-6 were measured in fasting plasma samples. MetS was defined according to the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria. Results: MetS was present in 37 % (IDF) and 33 % (AHA/NHLBI) of the study population (P < 0.001). Adiponectin was inversely associated with MetS (odds ratio, 95 % confidence interval: 0.829, 0.762- 0.902 for MetS-IDF, and 0.840, 0.772- 0.914 for MetS-AHA/NHLBI). Body mass index (BMI), waist circumference, high density lipoprotein (HDL)-cholesterol, triglyceride and insulin concentration mediated the association between adiponectin and MetS-IDF (z-test, standard error, P-value: 2.898, 0.012, 0.004, for BMI; 2.732, 0.012, 0.006 for waist circumference; 2.388, 0.011, 0.017 for HDL-cholesterol; 2.163, 0.010, 0.031 for triglyceride; 2.539, 0.010, 0.011 for insulin). Similarly, BMI, waist circumference, HDL-cholesterol and insulin concentration mediated the association between adiponectin and MetS-AHA/NHLBI (z-test, standard error, P-value: 2.633, 0.011, 0.008 for BMI; 2.441, 0.011, 0.015 for waist circumference; 1.980, 0.010, 0.048 for HDL-cholesterol; 2.225, 0.009, 0.026 for insulin). However, adiponectin remained significantly associated with MetS. IL-6 was not significantly associated with MetS. Conclusion: MetS components, in particular obesity and lipid indices, as well as serum insulin levels, mediate the association between adiponectin and MetS as defined by both the IDF and AHA/NHLBI criteria. © 2016 The Author(s)

Effect of fortified milk on lyso-platelet-activating factor acetyltranferase and lipoprotein-associated phospholipase A2 in hypercholesterolemic adults

Hypercholesterolemia is associated with subclinical inflammation, characterised by elevated proinflammatory mediators. Lyso-platelet-activating factor acetyltransferase (lyso-PAF AT) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are two key metabolic enzymes of platelet-activating factor (PAF), a potent inflammatory lipid mediator. Little information is available concerning the efficacy of a dietary intervention on the metabolism of PAF. The objective of the study was to evaluate the effect of fortified milk on the activity of these enzymes. Forty-three adults (mean age 49.8±8.1 years) with body mass index <35kg/m2, and total cholesterol >200 but <310mg/dL were randomised to two groups; (i) intervention group received 500mL/day (two glasses) of a low-fat milk fortified with phytosterols, linoleic and alpha linolenic acids, vitamin C, vitamin E, vitamin A, vitamin B6, vitamin B12, folic acid, magnesium and selenium (n=22), and (ii) placebo group received 500mL/day of a conventional low-fat milk (n=21) for 3 months. Outcome measures were the activities of lyso-PAF AT from leukocytes and serum Lp-PLA2 determined with established methods. None of the activities changed significantly during the study in the intervention group, lyso-PAF AT (95% confidence interval: -1.7, 2.3nmol/min/mg; p=0.246), and Lp-PLA2 (-7.8, 5.8nmol/min/mL, p=0.591). No difference was observed between the two groups. In conclusion, daily intake of two glasses of phytosterols, antioxidants, linoleic and linolenic acids via fortified milk for three months had no effect on the activity of either lyso-PAF AT or Lp-PLA2. Practical applications: Platelet-activating factor (PAF) was the first intact phospholipid known to have messenger functions in which the signaling results from the molecule binding to specific receptors on the plasma membrane or other membranes of the cell. It has a number of pro-inflammatory properties, and affects several critical points of atherogenesis including thrombosis, inflammation, and oxidation. Fortification of milk with nutrients that possess anti-inflammatory properties and administration to adults with elevated blood cholesterol could provide a means to controlling inflammatory process through the synthesis and degradation of PAF in a population group at risk for cardiovascular morbidity and mortality. (A) Lyso-PAF AT (lyso-PAF acetyltransferase) activity in nmol/min/mg, at baseline, and at the end of the 1st and 3rd months of the intervention period for placebo (PG: red line) and intervention group (PhG: blue line) separately (pfor effect of time>0.05). (B) Lp-PLA2 (lipoprotein-associated phospholipase A2) activity in nmol/min/mL at baseline, and at the end of the 1st and 3rd months of the intervention period for placebo (PG: red line) and intervention group (PhG: blue line) separately (pfor effect of time>0.05). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Amino acid profile and metabolic syndrome in a male Mediterranean population: A cross-sectional study

Background and aims The metabolic syndrome (MetS) refers to a cluster of clinically relevant factors that increases the risk of cardiovascular diseases and all-cause mortality. Circulating levels of several amino acids and metabolites related to one-carbon metabolism have been associated with cardiometabolic risk factors and MetS. We aimed to identify the amino acid profile that is significantly associated with MetS among an all male Mediterranean population. Methods and results One hundred middle-aged men (54.6 ± 8.9 years) participated in a cross-sectional study carried out during 2011–2012. The International Diabetes Federation (IDF) criteria were used to define MetS. Fasting plasma levels of 20 common amino acids and 15 metabolites related to amino acid and one-carbon metabolism were measured using gas chromatography (GC-MS/MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Principal components analysis was applied. Fifty-six participants fulfilled the IDF criteria for defining MetS. Five factors were extracted from the 35 measured metabolites. The branched-chain amino acids/aromatic amino acids (BCAA/AAA) related pattern and the glutamine/glycine/serine/asparagine (Gln/Gly/Ser/Asn) related pattern were significantly associated with MetS (odds ratio, 95% confidence interval; 6.41, 2.43–16.91, and 0.47, 0.23–0.96, respectively) after adjustment for age, current smoking status, physical activity level and medical treatment for hypertension, dyslipidaemia, type 2 diabetes mellitus. Further adjustment for liver function markers (i.e. glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and γ-glutamyltransferase), and plasma adiponectin levels did not significantly affect the associations. Conclusion The BCAA/AAA pattern was positively associated, while the Gln/Gly/Ser/Asn pattern was inversely associated with established cardiometabolic risk factors and MetS. Plasma adiponectin levels or markers of liver function did not significantly affect these associations. © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II Universit

N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion

Background N-acetylcysteine (NAC) is an antioxidant with direct and indirect antioxidant actions used in the clinical setting. Oxidative stress is known to play a pivotal role in the intestinal ischemia reperfusion (IIR). Therefore, we studied the effect of different pretreatment regimens with NAC on the IIR injury in rats. Materials and methods Thirty-five male Wistar rats were randomly assigned to five groups. In group sham, only laparotomy was performed. Group control underwent IIR without NAC. In the other groups, NAC was administered intraperitoneally with different regimens: 150 mg/kg before ischemia (NAC 150), 300 mg/kg before ischemia (NAC 300), and 150 mg/kg before ischemia plus 150 mg/kg 5 min before reperfusion (NAC 150 + 150). Measurements in tissues and blood were conducted at 4 h of reperfusion following exsanguination. Results Histological score of the liver was significantly improved in NAC 300 compared with control (1.7 ± 0.5 versus 2.9 ± 1.1, respectively, P = 0.05). In addition, NAC treatment significantly reduced liver transaminases in all groups of treatment, mostly in group NAC 300. Plasma malondialdehyde levels were lower with NAC treatment, although not statistically significant. Lung glutathione peroxidase was significantly increased in group NAC 300 (P = 0.04), while the other oxidation biomarkers showed no significant differences. Conclusions NAC exerts a significant protective role in liver injury following IIR, which seems to be independent of an intestinal protective effect. Additional administration of NAC before reperfusion was of no further benefit. The most effective regimen among the compared regimens was that of 300 mg/kg before ischemia. © 2016 Elsevier Inc

Adherence to Mediterranean diet and 10-year incidence (2002-2012) of diabetes: Correlations with inflammatory and oxidative stress biomarkers in the ATTICA cohort study

Background: The purpose of this work was to investigate the links between oxidative stress, inflammation and coagulation and their effect on Mediterranean diet-diabetes relationship. Methods: In 2001-2002, a random sample of 1514 men (18-87 years old) and 1528 women (18-89 years old) was selected to participate in the ATTICA study, where Athens is the major metropolis. A validated questionnaire was used to assess lifestyle and dietary factors. Adherence to Mediterranean diet was recorded using MedDietScore. Among others, oxidative stress and inflammatory biomarkers were recorded. During 2011-2012, the 10-year follow-up was performed. Diabetes incidence was defined according to the American Diabetes Association criteria. Results: A total of 191 incident cases of diabetes were documented, yielding an incidence of 12.9% (13.4% in men and 12.4% in women). Medium and high adherence was found to decrease diabetes risk by 49% (95% CI: 0.30, 0.88) and 62% (95% CI: 0.16, 0.88), respectively, compared with low adherence. A logarithmic trend between Mediterranean diet and diabetes incidence was also revealed (p for trend=0.042). Individuals with abnormal waist circumference (>94 for men, >80 for women) were benefited the most. Wholegrain cereals, fruits and legumes had the greatest predictive ability. The anti-diabetic effect of Mediterranean diet correlated with measurements of tumour necrosis factor-α, homocysteine and total antioxidant capacity. Conclusions: The reported results support the role of Mediterranean diet as a promising dietary tool for the primary prevention of diabetes, by attenuating inflammation and fostering total antioxidant capacity. This dietary pattern may have therapeutic potential for many cardiometabolic disorders associated with inflammation and/or oxidative stress. © 2016 John Wiley & Sons, Ltd

Metabolic syndrome and 10-year cardiovascular disease incidence: The ATTICA study

Aims: To evaluate the influence of metabolic syndrome (MetS) as well as inflammatory and renal markers on cardiovascular disease (CVD) incidence. Methods and results: During 2001-2002, 1514 men and 1528 women (>18y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, Greece, were enrolled. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. MetS was defined using three definitions, provided by the National Cholesterol Education Program Adult Treatment panel III (revised NCEP ATP III), the International Diabetes Federation (IDF) or the Harmonized definition. Furthermore, the contributory predictive role of C-reactive protein (CRP), inteleukin-6, uric acid and estimated glomerular filtration rate in the aforementioned models was evaluated. History of MetS-NCEP was positively associated with CVD, adjusting for potential confounding factors (OR:1.83, 95%CI:1.24-2.72). Not statistically significant associations with CVD incidence were observed when using the IDF or the Harmonized definition. Additionally, none of the added inflammatory and renal function markers mediated the influence of MetS on CVD incidence (all p's from Sobel test >0.40). C-statistic values for the MetS definitions used exceeded 0.789 (CI:0.751-0.827), indicating fair-to-good predictive probability of the models. Conclusion: Results of the present work revealed the negative impact of MetS-NCEP, but not of the other MetS definitions, on CVD incidence, a key-point that may help in better understanding the role of IDF and Harmonized MetS definitions on CVD. © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

Exploring the path of Mediterranean diet on 10-year incidence ofcardiovascular disease: The ATTICA study (2002-2012)

Background and aims: A Mediterranean diet has been associated with lower all-cause and cardiovascular disease (CVD) morbidity and mortality, but the clinical and behavioral pathway has not been well understood and appreciated. The aim of this work was to explore the path between adherence to a Mediterranean-type diet, lifestyle behaviors, clinical status, and a 10-year incidence of CVD. Methods and results: The ATTICA study was carried out in the Athens area during 2001-2002 and included 3042 participants free of CVD at baseline (49.8% men, aged 18-89). Adherence to a Mediterranean diet was assessed using the MedDietScore (range 0-55). During 2011-2012, 2583 out of the 3042 participants were found during the 10-year follow-up (15% lost to follow-up). Adherence to a Mediterranean diet decreased CVD risk (relative Risk (RR) per 1/55 unit = 0.96, 95% confidence interval (CI): 0.93, 1.00), independently of various sociodemographic, lifestyle, and clinical factors. Subgroup analyses revealed that participants with an unhealthy lifestyle (i.e., smokers, and obese and sedentary persons) remained protected from CVD through a greater adherence to a Mediterranean diet (RR for smokers = 0.92, 95%CI: 0.88, 0.97; RR for obese participants = 0.90, 95%CI: 0.82, 0.979; and RR for sedentary participants = 0.95, 95%CI: 0.90, 0.99). Path analysis revealed that adherence to a Mediterranean diet not only decreases the levels of C-reactive protein and interleukin-6 but also has an independent protective role against CVD risk per se (total effect of the MedDietScore on CVD = -0.003, 95%CI: -0.005 to 0.000). Conclusion: Adherence to a Mediterranean diet confers a considerable reduction on CVD risk, independent of various factors. Therefore, even subjects with unhealthy lifestyle behaviors may benefit from adherence to this diet, suggesting another dimension to prevention strategies. © 2014 Elsevier B.V

Dietary patterns and 10-year (2002-2012) incidence of type 2 diabetes: Results from the ATTICA cohort study

AIM: To identify dietary patterns among apparently healthy individuals and to determine their long-term effect on diabetes incidence. METHODS: During 2001-2002, a random sample of 3,042 men and women (18-89 years old), living in greater Athens, was randomly selected to participate in the study. During 2011-2012, the 10-year follow-up was performed in 2,583 participants (15% drop-out rate). After excluding participants with diabetes at baseline and those for whom no information on diabetes status was available at follow- up, the working sample consisted of 1,485 participants. Dietary habits were assessed by means of a validated semiquantitative, food frequency questionnaire. Factor analysis was performed to extract dietary patterns from 18 food groups. RESULTS: Diabetes diagnosis at follow-up was made in 191 participants, yielding an incidence rate of 12.9%. Six factors (i.e. dietary patterns) were identified that explained 54% of the variation in consumption. After adjusting for major confounders, and stratification by age-group, logistic regression revealed that the most healthful pattern consisted of the consumption of fruits, vegetables, legumes, bread, rusk, and pasta which reduced the 10-year diabetes risk by 40%, among participants aged 45-55 years. The association reached marginal statistical significance (95% CI: 0.34, 1.07), while no significant association was observed for the other age-groups. When the analysis was additionally adjusted for carbohydrate percentage, statistical significance was lost completely, suggesting a possibly mediating effect of this macronutrient. CONCLUSIONS: The results confirm the potentially protective effect of a plant-based dietary pattern in the primary prevention of diabetes, in particular among middle-aged people. Carbohydrate content may be a specific factor in this relationship; other micronutrients found in plant-based food groups may also play a role. © by Lab & Life Press/SBDR

Effects of alcohol consumption and the metabolic syndrome on 10-year incidence of diabetes: The ATTICA study

Aim: The purpose of this prospective study was to investigate the effect of alcohol consumption on the 10-year diabetes incidence. Methods: In 2001-2002, a random sample of 1514 men (18-89 years old) and 1528 women (18-87 years old) was selected to participate in the ATTICA study (Athens metropolitan area, Greece). Among various other characteristics, average daily alcohol intakes (abstention, low, moderate, high) and type of alcoholic drink were evaluated. Diabetes was defined according to American Diabetes Association criteria. During 2011-2012, the 10-year follow-up was performed. Results: The 10-year incidence of diabetes was 13.4% in men and 12.4% in women. After making various adjustments, those who consumed up to 1 glass/day of alcohol had a 53% lower diabetes risk (RR = 0.47; 95% CI: 0.26, 0.83) compared with abstainers, while trend analysis revealed a significant U-shaped relationship between quantity of alcohol drunk and diabetes incidence (P< 0.001 for trend). Specific types of drinks were not associated with diabetes incidence; however, a one-unit increase in ratio of wine/beer/vodka vs. other spirits was associated with an 89% lower risk of diabetes (RR = 0.11; 95% CI: 0.02, 0.67). The protective effect of low alcohol consumption on diabetes incidence was more prominent among individuals with stricter adherence to the Mediterranean diet (RR = 0.08; 95% CI: 0.011, 0.70) and without the metabolic syndrome (RR = 0.34; 95% CI: 0.16, 0.70). Conclusion: This work revealed the protective effect of modest alcohol consumption of particularly wine and beer against the long-term incidence of diabetes, possibly due to their pleiotropic health effects. © 2014 Elsevier Masson SAS

Metabolic syndrome, adherence to the Mediterranean diet and 10-year cardiovascular disease incidence: The ATTICA study

Background and aims: To better understand the metabolic syndrome (MS) spectrum through principal components analysis and further evaluate the role of the Mediterranean diet on MS presence. Methods: During 2001-2002, 1514 men and 1528 women (>18y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, Greece, were enrolled. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. MS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised NCEP ATP III) definition. Adherence to the Mediterranean diet was assessed using the MedDietScore (range 0-55). Results: Five principal components were derived, explaining 73.8% of the total variation, characterized by the: a) body weight and lipid profile, b) blood pressure, c) lipid profile, d) glucose profile, e) inflammatory factors. All components were associated with higher likelihood of CVD incidence. After adjusting for various potential confounding factors, adherence to the Mediterranean dietary pattern for each 10% increase in the MedDietScore, was associated with 15% lower odds of CVD incidence (95%CI: 0.71-1.06). For the participants with low adherence to the Mediterranean diet all five components were significantly associated with increased likelihood of CVD incidence. However, for the ones following closely the Mediterranean pattern positive, yet not significant associations were observed. Conclusion: Results of the present work propose a wider MS definition, while highlighting the beneficial role of the Mediterranean dietary pattern. © 2015 Elsevier Ireland Ltd