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Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food., Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study., Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI., Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m 2 (0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up., Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited., Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population., Methods: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models., Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (β-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015)., Conclusion: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Arterial stiffness is linked with the development of cardiovascular and noncardiovascular diseases. In clinical practice, measurement of carotid-femoral pulse wave velocity (cf-PWV) has become a widely used study for the assessment of cardiovascular risk in elderly population. Our aim was to evaluate whether maintaining a healthy life, based on Mediterranean Diet (MedDiet) and regular practice of physical activity, are associated with arterial stiffness in an elderly, metabolically healthy with overweight or obesity (MHOe) population., Individuals and Methods: A transversal, analytical-descriptive study in MHOe population (aged ≥65 years) with a BMI at least 27 kg/ m 2 who had one or less of the following cardiometabolic disorders: fasting plasma glucose at least 100 mg/dl, blood pressure at least 135/85 mmHg (or the use of blood pressure-lowering agents), low high-density lipoprotein (HDL) cholesterol (≤ 40 mg/dl for men, ≤50 mg/dl for women) or triglycerides at least 150 mg/dl (or the use of lipid-lowering therapies) was conducted. Blood pressure, height, weight, BMI, waist to hip ratio (WHR), practice of physical activity, MedDiet adherence and food intake along with cf-PWV were analysed., Results: One hundred and fifty-eight MHOe individuals (age: 72.2 ± 5.0 years, BMI: 31.6 ± 3.8 kg/m 2 ) were recruited. One hundred and nine of them were younger than 75 years of age (young-old, age: 69.3 ± 2.8 years and BMI: 32.0 ± 3.9 kg/m 2 ) and 49 of them aged 75 years or older (old-old, age: 78.1 ± 2.9 years and BMI: 30.7 ± 3.6 kg/m 2 ). All population showed a strong adherence to the Med Diet due major consumption of homemade meal, olive oil and lean meats. In addition, they presented an important practice of all intensities of physical activity. Young-old individuals had a cf-PWV of 9.7 ± 2.2 m/s and old-old individuals had a cf-PWV of 11.1 ± 4.4 m/s. In all populations, a negative correlation between cf-PWV and BMI ( r  = -0.17, P  = 0.04) and a positive correlation with WHR in men ( r  = 0.18, P  = 0.03) was found. WHR shows a significantly positive correlation with the cf-PWV values in old-old women participants ( r  = 0.41, P  = 0.008). On the other side, only vigorous physical activity showed a negative correlation with cf-PWV in all population and in young-old individuals ( r  = -0.20; P  = 0.02 and r  = -0.22; P  = 0.03, respectively)., Conclusion: Healthy lifestyle habits based on MedDiet adherence and regular practice of physical activity are associated with lower arterial stiffness in a metabolically healthy population with overweight or obesity older than 65 years compared with data from other elderly populations previously reported in the literature., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Obesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain)., Subjetcs and Methods: Subjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C <40mg/dL in men and <50mg/dL women; and fasting blood glucose ≥100mg/dL. Selected subjects underwent a personalized intensive lifestyle modification. Anthropometric measurements, PA, MedDiet adherence, analytical parameters, and inflammatory biomarkers were analyzed after 12 months of intervention., Results: 166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p < 0.0001), aged 71.7±5.2 years old (65 to 87 years old) were included in the study. After 12 months of intervention, only the waist circumference was significantly reduced in all the population (-2.5 cm, p<0.0001), although weight and BMI were maintained. MedDiet adherence increased significantly (p<0.001), but all intensity levels of PA decreased significantly (p<0.001). Concerning inflammatory biomarkers, only TNFa serum increased their levels after the intervention (p<0.001). Regarding the adipokine profile, adiponectin concentrations experienced a significant increment (p<0.001); besides, resistin concentrations decreased significantly (p<0.001). In this sense, only TNFa, adiponectin, and resistin correlated with PA. Adiponectin also correlates with insulin, triglycerides and HDL-c in baseline conditions and after 12 months of intervention; CRP, IL-6, TNFa, adiponectin, and resistin concentrations correlated with anthropometric parameters and some intensities of PA. In addition, adiponectin levels correlates with insulin, triglycerides and HDL-c. In baseline conditions, resistin levels correlated positively with TNFa (p = 0.01) and CRP (p<0.0001) levels. TNFa and IL-6 correlated positively with CRP (p = 0.03 and p<0.0001, respectively). After 12 months of intervention, only IL-6 correlated positively with CRP (p = 0.006). In addition, adipokines levels correlated positively during the process of lifestyle modification. However, during this process, only IL-6 correlated positively with itself (p<0.0001) and with CRP (p = 0.03)., Conclusion: Healthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders., Competing Interests: The authors have declared that no competing interests exist.

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 ± 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D.

Impairment of the arteries is a product of sustained exposure to various deleterious factors and progresses with time; a phenomenon inherent to vascular aging. Oxidative stress, inflammation, the accumulation of harmful agents in high cardiovascular risk conditions, changes to the extracellular matrix, and/or alterations of the epigenetic modification of molecules, are all vital pathophysiological processes proven to contribute to vascular aging, and also lead to changes in levels of associated circulating molecules. Many of these molecules are consequently recognized as markers of vascular impairment and accelerated vascular aging in clinical and research settings, however, for these molecules to be classified as biomarkers of vascular aging, further criteria must be met. In this paper, we conducted a scoping literature review identifying thirty of the most important, and eight less important, biomarkers of vascular aging. Herein, we overview a selection of the most important molecules connected with the above-mentioned pathological conditions and study their usefulness as circulating biomarkers of vascular aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gopcevic, Gkaliagkousi, Nemcsik, Acet, Bernal-Lopez, Bruno, Climie, Fountoulakis, Fraenkel, Lazaridis, Navickas, Rochfort, Šatrauskienė, Zupkauskienė and Terentes-Printzios.)

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of death worldwide. High levels of total cholesterol-and of low-density lipoprotein cholesterol in particular-are one of the main risk factors associated with ASCVD. Statins are first-line treatment for hypercholesterolemia and have been proven to reduce major vascular events in adults with and without underlying ASCVD. Findings in the literature show that statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged people, but their benefits in older adults are not as well-established, especially in primary prevention. Furthermore, many particularities must be considered regarding their use in old subjects, such as age-related changes in pharmacokinetics and pharmacodynamics, comorbidities, polypharmacy, and frailty, which decrease the safety and efficacy of statins in this population. Myopathy and a possible higher risk of falling along with cognitive decline are classic concerns for physicians when considering statin use in the very old. Additionally, some studies suggest that the relative risk for coronary events and cardiovascular mortality associated with high levels of cholesterol decreases after age 70, making the role of statins unclear. On the other hand, ASCVD are one of the most important causes of disability in old subjects, so cardiovascular prevention is of particular interest in this population in order to preserve functional status. This review aims to gather the current available evidence on the efficacy and safety of statin use in very old patients in both primary and secondary prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cobos-Palacios, Sanz-Cánovas, Muñoz-Ubeda, Lopez-Carmona, Perez-Belmonte, Lopez-Sampalo, Gomez-Huelgas and Bernal-Lopez.)

The SARS-CoV-2 pandemic led to lockdowns, which affected the elderly, a high-risk group. Lockdown may lead to weight gain due to increased food intake and reduced physical activity (PA). Our study aimed to analyze the impact of a 12-month lifestyle intervention on a metabolically healthy overweight/obese elderly (MHOe) population and how the lockdown by COVID-19 affected this program. Methods: MHOe participants (65-87 years) were recruited to participate in a lifestyle modification intervention based on the Mediterranean diet (MedDiet) and regular PA. Participants were classified into two groups: young-old (<75 years) or old-old (≥75 years). Anthropometric and clinical characteristics, energy intake, and energy expenditure were analyzed at baseline and after 12 months of intervention. Results: The final sample included 158 MHOe participants of both sexes (age: 72.21 ± 5.04 years, BMI: 31.56 ± 3.82 kg/m 2 ): 109 young-old (age: 69.26 ± 2.83 years, BMI: 32.0 ± 3.85 kg/m 2 ) and 49 old-old (age: 78.06 ± 2.88 years, BMI: 30.67 ± 3.64 kg/m 2 ). After 12 months of intervention and despite lockdown, the young-old group increased MedDiet adherence (+1 point), but both groups drastically decreased daily PA, especially old-old participants. Fat mass significantly declined in the total population and the young-old. Depression significantly increased (26.9% vs. 21.0%, p < 0.0001), especially in the old-old (36.7% vs. 22.0%, p < 0.0001). No significant changes were found in the glycemic or lipid profile. Conclusions: This study indicates that ongoing MedDiet intake and regular PA can be considered preventative treatment for metabolic diseases in MHOe subjects. However, mental health worsened during the study and should be addressed in elderly individuals.

Scope: Plasma fatty acids (FAs) are associated with the development of cardiovascular diseases and metabolic syndrome. The aim of our study is to assess the relationship between fruit and vegetable (F&V) consumption and plasma FAs and their subtypes., Methods and Results: Plasma FAs are assessed in a cross-sectional analysis of a subsample of 240 subjects from the PREDIMED-Plus study. Participants are categorized into four groups of fruit, vegetable, and fat intake according to the food frequency questionnaire. Plasma FA analysis is performed using gas chromatography. Associations between FAs and F&V consumption are adjusted for age, sex, physical activity, body mass index (BMI), total energy intake, and alcohol consumption. Plasma saturated FAs are lower in groups with high F&V consumption (-1.20 mg cL -1 [95% CI: [-2.22, -0.18], p-value = 0.021), especially when fat intake is high (-1.74 mg cL -1 [95% CI: [-3.41, -0.06], p-value = 0.042). Total FAs and n-6 polyunsaturated FAs tend to be lower in high consumers of F&V only in the high-fat intake groups., Conclusions: F&V consumption is associated with lower plasma saturated FAs when fat intake is high. These findings suggest that F&V consumption may have different associations with plasma FAs depending on their subtype and on the extent of fat intake., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Purpose: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS)., Methods: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment., Results: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A)., Conclusions: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS., Trial Registration: ISRCTN89898870. Registration date: July 24, 2014., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aim of this study was to analyze effects of a 12-month lifestyle modification that involved a Mediterranean diet (MedDiet) and physical activity (PA) program in a population of metabolically healthy obese children (MHOCh)., Methods: We included a population of MHOCh with ≤1 of the following criteria: waist circumference and blood pressure ≥90 percentile, triglycerides >150 mg/dL, high-density lipoprotein-cholesterol (HDL-c) <40 mg/dL, or impaired fasting glucose. After 12 months of intensive lifestyle modification, anthropometric measurements, glycemic and lipid profiles, adherence to the MedDiet, energy intake, PA, body composition, and carotid intima-media thickness (cIMT) were analyzed., Results: One hundred thirty-one MHOCh (70 boys and 61 girls; P = 0.65, age: 7.9 ± 1.3 years, body mass index [BMI]: 24.7 ± 3.5 kg/m2) were included. After 12 months of intervention, a significant decrease in standard deviation (SD) units of body weight (-0.5 ± 0.1; P < 0.001) and BMI (-0.5 ± 0.1; P < 0.001) were observed in the total population. A significant improvement in adherence to the MedDiet (+2 points) and a significant reduction in protein, fatty acids, total fat, and cholesterol intake in the entire population were observed. All participants did more moderate-vigorous PA, which led to a significant increase in lean and total mass and decrease in total fat. Significant improvements in the glycemic profile (insulin levels [-6.6 μIU/mL, P < 0.001] and HOMA index [-1.2, P < 0.001]) were observed. Participants with pathological cIMT values reduced this cardiovascular predictor to normal values., Conclusions: A 12-month lifestyle modification intervention involving weight loss with MedDiet and PA in MHOCh yielded improvements in MedDiet adherence, lipid intake, moderate-vigorous PA, body composition, insulin resistance, and cIMT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aim: Arteriosclerotic cardiovascular disease, one of the world's leading causes of death, first manifests itself at an early age. The identification of children who may have increased cardiovascular risk in the future could be an important prevention strategy. Our aim was to assess the clinical, analytical, and dietary variables associated with arterial stiffness (AS), measured by carotid-femoral pulse wave velocity (cfPWV) in a prepubescent population with metabolically healthy obesity (MHO)., Subjects and Methods: A cross-sectional study in prepubescent subjects with obesity who had ≤1 metabolic syndrome criteria (abdominal perimeter and blood pressure ≥90th percentile, triglycerides >150 mg/dL, HDL-cholesterol <40 mg/dL, fasting plasma glucose ≥100 mg/dL) was conducted. Adherence to Mediterranean Diet, blood pressure, BMI, waist/height ratio (WHtR), glycemic status, lipid profile, and cfPWV were analyzed. 75 MHO children (boys: 43; girls: 32; p = 0.20) (age = 10.05 ± 1.29 years; BMI = 25.29 ± 3.5 kg/m2) were included., Results: We found a positive correlation between cfPWV and weight (r = 0.51; p < 0.0001), BMI (r = 0.44; p < 0.0001), WHtR (r = 0.26; p = 0.02), fasting insulin levels (r = 0.28; p = 0.02), and insulin resistance (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index) (r = 0.25; p = 0.04). Multiple linear regression analysis identified BMI and HOMA-IR as independent parameters associated with cfPWV., Conclusions: Prepubescent children with obesity who were shown to be metabolically healthy presented with arterial stiffness, which is closely related to BMI and the state of insulin resistance.

Background: Metabolically healthy obesity (MHO) is a considerably controversial concept as it is considered a transitory condition towards the development of different pathologies (type 2 diabetes, insulin resistance, or cardiovascular disease). MHO is closely related to lifestyle and environmental factors. Epigenetics has become an essential biological tool to analyze the link between obesity and metabolic status. The aim of this study was to determine whether MHO status is conditioned by the DNA methylation (DNAm) of several genes related to lipid metabolism (lipoprotein lipase, retinoid X receptor alpha, liver X receptor, stearoyl-CoA desaturase, sterol regulatory element binding factor 1), and inflammation (LEP) in peripheral blood mononuclear cells (PBMCs) from 131 prepubertal subjects with MHO phenotype after lifestyle modifications with personalized Mediterranean diet (MedDiet) combined with a physical activity (PA) program., Results: The DNAm of all studied genes were significantly modified in the population after 12 months of lifestyle modifications (MedDiet and PA). In addition, associations were found between the DNAm studies and BMI, homeostatic model assessment of insulin resistance, monounsaturated fatty acid and polyunsaturated fatty acid, moderate-vigorous PA, fat mass, and adherence to MedDiet., Conclusions: It was found that DNAm of genes related to lipid metabolism and inflammation are also present in childhood and that this methylation profile can be modified by interventions based on MedDiet and PA.

Purpose: To assess the association between the consumption of non-soy legumes and different subtypes of non-soy legumes and serum uric acid (SUA) or hyperuricemia in elderly individuals with overweight or obesity and metabolic syndrome., Methods: A cross-sectional analysis was conducted in the framework of the PREDIMED-Plus study. We included 6329 participants with information on non-soy legume consumption and SUA levels. Non-soy legume consumption was estimated using a semi-quantitative food frequency questionnaire. Linear regression models and Cox regression models were used to assess the associations between tertiles of non-soy legume consumption, different subtypes of non-soy legume consumption and SUA levels or hyperuricemia prevalence, respectively., Results: Individuals in the highest tertile (T3) of total non-soy legume, lentil and pea consumption, had 0.14 mg/dL, 0.19 mg/dL and 0.12 mg/dL lower SUA levels, respectively, compared to those in the lowest tertile (T1), which was considered the reference one. Chickpea and dry bean consumption showed no association. In multivariable models, participants located in the top tertile of total non-soy legumes [prevalence ratio (PR): 0.89; 95% CI 0.82-0.97; p trend = 0.01, lentils (PR: 0.89; 95% CI 0.82-0.97; p trend = 0.01), dry beans (PR: 0.91; 95% C: 0.84-0.99; p trend = 0.03) and peas (PR: 0.89; 95% CI 0.82-0.97; p trend = 0.01)] presented a lower prevalence of hyperuricemia (vs. the bottom tertile). Chickpea consumption was not associated with hyperuricemia prevalence., Conclusions: In this study of elderly subjects with metabolic syndrome, we observed that despite being a purine-rich food, non-soy legumes were inversely associated with SUA levels and hyperuricemia prevalence., Trial Registration: ISRCTN89898870. Registration date: 24 July 2014.

Background & Aims: The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity., Methods: A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: <10% (low weight loss group, LWL) and >10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated., Results: Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG., Conclusions: Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: For the metabolically healthy obese (MHO) subjects, it is unclear whether weight loss provides cardiometabolic benefits. Our objective was to evaluate whether changes in adipokine and inflammatory biomarker levels were related to lifestyle modification (with Mediterranean diet and physical exercise program)., Methods: 115 women (35-55 years) with BMI of 30-40 kg/m 2 and ≤1 metabolic syndrome criteria were included. After a 2-year intervention, participants were classified by percent weight loss: Group 1, <5%; Group 2, ≥5%-<10%; and Group 3, ≥10%. Anthropometric data, inflammatory biomarker (IL-6, TNFa, and hsCRP) and adipokine levels (adiponectin and resistin), and lifestyle program adherence at baseline and 2 years were analyzed., Results: The final sample comprised 67 women. 23 (38.3%) lost <5%, 22 (36.7%) lost ≥5%-<10%, and 22 (36.7%) lost ≥10% of baseline weight. After 2 years, in Group 1, adiponectin, hsCRP, IL-6, and TNFa decreased (-1.2 ng/ml, p = 0.003; -2.1 mg/l, p = 0.003; -2.4 pg/ml, p < 0.001; and -2.4 pg/ml, p = 0.001, respectively) and resistin increased (+2.4 ng/ml, p < 0.001). In Group 2, hsCRP and IL-6 decreased (-2.0 mg/l, p = 0.009 and -2.6 pg/ml, p = 0.001) but TNFa increased (+0.2 pg/ml, p = 0.02). In Group 3, resistin increased (+3.5 ng/ml, p < 0.001) but hsCRP, IL-6, and TNFa decreased (-2.0 mg/l, p = 0.009; -2.5 pg/ml, p < 0.001; and -4.1 pg/ml, p < 0.001). Adiponectin, hsCRP, and physical exercise correlated significantly to subjects' dietary adherence., Conclusion: Weight loss reduces inflammatory biomarkers in the MHO but induces a deterioration in the adipokine profile, which does not improve with diet and exercise intervention. These findings allow us to clarify mechanisms behind inflammation and metabolic disorder genesis so as to prevent development of obesity-associated comorbidities.

Objective: Polyamines are naturally occurring cationic molecules present in all living cells. Dysregulation of circulating polyamines has been reported in several conditions, but little is known about the levels of serum polyamines in chronic metabolic disorders such as type 2 diabetes (T2D). Therefore, the aim of this study was to evaluate the polyamine-related metabolome in a cohort of metabolic syndrome individuals with and without T2D. Design and methods: This was a nested case⁻control study within the PREDIMED-Plus trial that included 44 patients with T2D and 70 patients without T2D. We measured serum levels of arginine, ornithine, polyamines, and acetyl polyamines with an ultra-high performance liquid chromatography tandem mass spectrometry platform. Results: Our results showed that serum putrescine, directly generated from ornithine by the catalytic action of the biosynthetic enzyme ornithine decarboxylase, was significantly elevated in patients with T2D compared to those without T2D, and that it significantly correlated with the levels of glycosylated hemoglobin (HbA1c). Correlation analysis revealed a significantly positive association between fasting insulin levels and spermine. Multiple logistic regression analysis (adjusted for age, gender and body weight index) revealed that serum putrescine and spermine levels were associated with a higher risk of T2D. Conclusions: Our study suggests that polyamine metabolism is dysregulated in T2D, and that serum levels of putrescine and spermine are associated with glycemic control and circulating insulin levels, respectively.

Little is known regarding metabolic benefits of weight loss (WL) on the metabolically healthy obese (MHO) patients. We aimed to examine the impact of a lifestyle weight loss (LWL) treatment on the plasma metabolomic profile in MHO individuals. Plasma samples from 57 MHO women allocated to an intensive LWL treatment group (TG, hypocaloric Mediterranean diet and regular physical activity, n = 30) or to a control group (CG, general recommendations of a healthy diet and physical activity, n = 27) were analyzed using an untargeted 1 H NMR metabolomics approach at baseline, after 3 months (intervention), and 12 months (follow-up). The impact of the LWL intervention on plasma metabolome was statistically significant at 3 months but not at follow-up and included higher levels of formate and phosphocreatine and lower levels of LDL/VLDL (signals) and trimethylamine in the TG. These metabolites were also correlated with WL. Higher myo-inositol, methylguanidine, and 3-hydroxybutyrate, and lower proline, were also found in the TG; higher levels of hippurate and asparagine, and lower levels of 2-hydroxybutyrate and creatine, were associated with WL. The current findings suggest that an intensive LWL treatment, and the consequent WL, leads to an improved plasma metabolic profile in MHO women through its impact on energy, amino acid, lipoprotein, and microbial metabolism.

Objective: There is a lack of consensus when it comes to establishing the biochemical parameters that define metabolically healthy obese (MHO) subjects. Indeed, most studies do not include subjects' lipid profiles. Our objective was to characterize lipoprotein size, particle and subclass concentration using 1 H NMR in MHO women after two years of weight loss with a hypocaloric Mediterranean diet and physical exercise., Methods: 115 non-diabetic women (aged 35-55 years) with a body mass index (BMI) of 30-40 kg/m 2 and ≤1 of the following criteria: blood pressure ≥135/85 mmHg, fasting plasma glucose ≥100 mg/dL, HDL cholesterol ≤50 mg/dL and triglycerides ≥150 mg/dL were included. After two years of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5%-<10% and ≥10%. Lipoprotein size, particle and subclass concentrations were measured using 1 H NMR., Results: The final population, after dropouts, were 67 women (age: 44.5 ± 3.7 years, BMI: 36.3 ± 4.7 kg/m 2 ), of whom 23 (38.3%) lost <5%, and 22 (36.7%), lost ≥5% to <10% and ≥10% of baseline body weight, respectively. The lipid profile showed no significant changes after intervention, especially in small LDL particles or in production of HDL. The diameter of LDL and HDL particles did not change after two years of a Mediterranean diet and physical exercise., Conclusion: These results indicate that intensive lifestyle modification does not produce significant changes in the lipid profile of MHO women. Levels of more atherogenic or atheroprotective particles did not change after two years, despite the intervention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rationale: CD36 is a scavenger receptor located on monocytes which is involved in foam cell transformation., Aim: To evaluate CD36 expression under different glycemic states in both healthy subjects and in atherosclerotic patients., Subjects and Methods: In order to evaluate the possible effects of hyperglycemia on CD36 expression in healthy subjects, an in vitro experiment was carried out using monocyte in three different conditions: extreme hyperglycemia (HG), euglycemia (EG) and in the absence of glucose. On the other hand, three groups of atherosclerotic patients were evaluated according to their glycemic conditions: normoglycemic (NG), prediabetic (preDM) and diabetic (DM) patients. CD36 expression (mRNA, non-glycated and glycated protein) was analyzed in monocytes., Results: CD36 mRNA expression in the in vitro experiment peaked at 4 and 24 h under HG conditions. No differences in mRNA levels were found in the EG and control group. The level of non-glycated proteins was higher in HG and EG conditions compared with control group. Glycated protein expression was inhibited by glucose in a sustained manner. In atherosclerotic patients, a significant association was observed when comparing glycated CD36 protein expression in DM with NG patients (p = 0.03). No significant differences were found in mRNA and non-glycated CD36 expression in these patients. Moreover, BMI, insulin, weight and treatment were shown to be related to CD36 expression (mRNA, non-glycated and glycated protein levels, depending of the case) in atherosclerotic patients., Conclusions: Hyperglycemia is an important modulator of CD36 mRNA and non-glycated protein expression in vitro, increasing de novo synthesis in healthy subjects. In atherosclerotic patients, there are progressive increases in CD36 receptors, which may be due to a post-translational stimulus.

Obesity is associated with an atherogenic lipid profile. No data exists on lipoprotein particle profiles in metabolically healthy obese (MHO) individuals. Our aim is to characterize lipoprotein size, particle, and subclass concentrations in MHO women after 3 months of weight loss through dietary restriction and physical exercise.A total of 115 nondiabetic women (aged 35-55 years) with a body mass index (BMI) of 30 to 40 kg/m and ≤1 of the following criteria: blood pressure ≤135/85 mm Hg, fasting plasma glucose ≤100 mg/dL, HDL-cholesterol ≤50 mg/dL, and triglycerides ≤150 mg/dL were included. After 3 months of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5% to <10%, and ≥10%. Lipoprotein size, particle, and subclass concentrations were measured using H NMR.The final sample, after dropouts, comprised 104 women (age: 44.4 ± 3.7 years, BMI: 36.3 ± 4.7 kg/m), of whom 47 (45.2%), 27 (26%), and 30 (28.8%) lost <5%, ≥5% to <10%, and ≥10% of baseline body weight, respectively. All participants experienced significant weight loss and decreases in BMI. The lipid profiles showed an increase in small, medium, and large very low density lipoprotein (VLDL) particles in all groups of study with the exception of small VLDL particles in women with ≥10% of weight loss, in which it decreased. The number of VLDL particles decreased in women who had ≥10% weight loss. On the other hand, we detected a decrease in all low density lipoprotein (cLDL) and high density lipoprotein (cHDL) concentrations.These results indicate that intensive lifestyle modification alters lipid profiles. In particular, it decreases small LDL and HDL particle numbers and does not increase medium or large HDL particles numbers.

Aim: Cilostazol is a drug widely used to treat peripheral arterial disease (PAD) in patients with advanced atherosclerosis. It is an inhibitor of platelet aggregation and causes arterial vasodilatation. It has been speculated that cilostazol might act to improve oxidative stress in these patients., Methods: We analyzed 25 patients with demonstrated lower limb peripheral arterial disease to determine whether lipid peroxidation (LPO) or total antioxidant capacity (TAC) were modified after 6 months of cilostazol treatment (postintervention phase) with respect to the basal phase., Results: Analysis of plasma samples determined that LPO levels decreased significantly over the postintervention phase (26±15 vs. 11±7 pM, P=0.0003). However, when TAC levels were analyzed, no significant differences were observed (0.80±0.21 vs. 0.85±0.17 mM, P=0.42). Under basal conditions, LPO showed a positive correlation to treatment as judged by the ankle-brachial index (r=0.800, P=0.002) as well as uric acid (r=0.508, P=0.03) and CRP (r=0.481, P=0.05) levels. In contrast, TAC negatively correlated with triglycerides (r=-0.879, P<0.0001) and microalbuminuria (r=-0.868, P<0.0001). In the postintervention phase, TAC negatively correlated with HbA1c (r=-0.570, P=0.02) and triglycerides (r=-0.864, P<0.0001)., Conclusions: Our data indicate that cilostazol treatment does not improve oxidative stress in PAD patients after 6 months of treatment. However, lipid peroxidation and total antioxidant capacity were affected by cilostrazol treatment, which could be related to altered reactive oxygen species production. Further research may be needed to determine the critical dose of cilostazol to clarify the protective role of this drug in PAD., (© 2014 John Wiley & Sons Ltd.)

Background: The existence of seasonal variability in patients with acute pulmonary embolism (PE) has been debated for years, with contradictory results. The aim of this study was to identify the trend and possible existence of a seasonal pattern in hospitalizations for PE in Spain., Methods: We analyzed the hospital discharge database of the Spanish National Health System from 2001 to 2010. Patients aged > 14 years diagnosed with PE were selected and a time series was constructed considering mean daily admissions for PE by month. The trend and seasonality factor of the series were determined using time-series analysis, and time-series modeling was used for analysis. Exponential smoothing models and the autoregressive integrated moving average test were used to generate a predictive model., Results: From 2001 to 2010, there were 162,032 diagnoses of PE (5.07 per 1000 hospitalizations). In 105,168 cases, PE was the reason for admission. The PE diagnosis rate ranged from 4.14 per 1000 in 2001 to 6.56 per 1000 in 2010; and hospital admissions due to PE ranged from 2.67 to 4.28 per 1000 hospital discharges. Time-series analysis showed a linear increase in the incidence and a significant seasonal pattern with 17% more admissions in February and 12% fewer in June-July with respect to the central tendency (difference from February to June, 29%)., Conclusions: The incidence of hospitalizations for PE showed a linear increase and a seasonal pattern, with the highest number of admissions in winter and the lowest number in summer., (© 2014 International Society on Thrombosis and Haemostasis.)

We report the first case of late presentation of familial aortic coarctation, a rare cause of hypertension. Diagnosis of familial aortic coarctation in the elderly is exceptional, given that in the absence of endovascular or surgical repair patients do not usually survive beyond 50 years of age. Our case concerns a 72-year-old woman with hypertension of long evolution, control of which improved markedly after endovascular repair of the coarctation. Her son had undergone surgery for repair of aortic coarctation at the age of 23 years.

Corticosteroid-induced hyperglycemia is a common medical problem that can lead to frequent emergency room visits, hospital admissions and prolonged hospital stay, in addition to the well known morbidity associated with hyperglycemia. However, the diagnosis and treatment of corticosteroid-induced hyperglycemia is surprisingly undervalued by most professionals, probably because of the lack of quality studies to determine specific strategies of action. In the present review, we discuss the pathophysiology of corticosteroid-induced hyperglycemia, focusing on diverse patterns of hyperglycemia induced by the different formulations, and provide clues for diagnosis based on the duration of treatment and the administration schedule of corticosteroids. We propose a treatment strategy based on both the pathophysiology of the process and the mechanism of action of different corticosteroids, and take into account dosing and administration timing to predict the duration of therapy. Finally, we propose treatment goals that differ slightly between the transient and continuous use of corticosteroids based on evidence from clinical practice guidelines of diabetes care both in ambulatory and hospital settings., (© 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

In hospitalized diabetic patients, the recommended insulin therapy is basal bolus plus correction-dose regimen instead of sliding-scale insulin. The purpose of this study was to evaluate the effect of the implementation of a new protocol based on basal bolus therapy on managing diabetes in a university hospital setting. We performed a cross-sectional study before and 12 months after a 4-month intervention period to implement a basal bolus regimen in hospitalized patients. Non-critical patients admitted into the hospital for at least 72 h were included. Changes in prescribing habits, glucose control and incidence of hypoglycemia were evaluated. An increase in the use of the new protocol and a decrease in sliding scale were observed after the intervention. In the pre-intervention group, a total of 59.2% glucose readings were between 70 and 180 mg/dL versus 57.1% after the intervention, without observing statistical differences. Significant reductions in hypoglycemia between pre- and post-intervention (13.04 vs. 4.08%, p = 0.0215) were observed. The percentage of hospitalized diabetic patients who had HbA1c was 10.43 and 4.08% in pre- and post-intervention phases, respectively. The protocol showed beneficial outcomes in terms of fewer hypoglycemia episodes and reflected a change in prescription habits, but it did not improve glycemic control. Furthermore, the percentage of patients who had an HbA1c test during their hospitalization remained very low after the intervention. This fact may seriously limit the correct management of hyperglycemia after the hospital discharge.

Aims: To analyze the seasonal variations in A1c levels among a southern European diabetic population., Methods: We examined all monthly-grouped A1c determinations from diabetic patients during the period 2006-2011, in a region of southern Spain., Results: There were 61,329 records available. The mean A1c value was 56mmol/mol (7.2%±1.7%) (95% CI, 55-56mmol/mol (7.2%-7.3%), with a range of 0.2%. The highest value was in February and the lowest in July (56mmol/mol (7.3%) and 54mmol/mol (7.1%), respectively) (P<0.01). However, spectral analysis and correlation coefficients did not reach significance, and the series presented no seasonal pattern., Conclusions: In our area, although the A1C levels have some monthly fluctuation they show no significant seasonal pattern. Thus, the seasonal fluctuation of HbA1c is not a limitation for decision making in clinical practice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To study the prevalence and correlates of body size phenotypes in an adult Spanish population., Methods: We undertook a cross-sectional analysis in a random sample of 2,270 individuals. We defined six body size phenotypes based on body mass index category (normal-weight, 18.5 to 24.9 kg/m2; overweight, 25 to 29.9 kg/m2; obese, ≥30.0 kg/m2) and the presence of ≤1 (metabolically healthy) or ≥2 (metabolically abnormal) cardiometabolic abnormalities: metabolically healthy normal-weight (MHNW), metabolically abnormal normal-weight (MANW), metabolically healthy overweight (MHOW), metabolically abnormal overweight (MAOW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). We considered four cardiometabolic abnormalities: systolic and/or diastolic blood pressure ≥130/85 mm Hg, triglycerides ≥150 mg/dL, high-density-lipoprotein cholesterol levels <40/<50 mg/dL in men/women, and elevated glucose (fasting plasma glucose ≥100 mg/dL or previous diabetes)., Results: The prevalence of the MHO, MHOW, and MANW phenotypes was 2.2, 13.9, and 7.9%, respectively. Whereas 9.6% of obese and 32.6% of overweight individuals were metabolically healthy, 21.3% of the normal-weight subjects were metabolically abnormal. A multivariate regression model (adjusted for age, sex, and waist circumference) showed that age >40 years, male sex, and higher waist circumference were independently associated with the metabolically abnormal phenotype MANW, whereas younger age, female sex, and lower waist circumference were independently associated with the metabolically healthy phenotypes., Conclusion: The prevalence of MHO in our population is low and is more common in women and younger people. In contrast, a high proportion of normal-weight individuals (mainly over 40 years of age) in our population show cardiometabolic abnormalities.

The mechanisms involved in the progression to overt diabetes in pre-obese subjects remain unclear. Therefore, a nontargeted evaluation of differences in the protein abundance of visceral adipose tissue (VAT) obtained from pre-obese diabetic subjects and pre-obese subjects showing normal glucose tolerance may provide novel insights on the molecular processes involved in the progression to overt diabetes in pre-obesity. Diabetic patients showed increased VAT abundance of glutathione S-transferase Mu 2, peroxiredoxin-2, antithrombin-III, apolipoprotein A-IV, Ig κ chain C region, mitochondrial aldehyde dehydrogenase and actin, and decreased abundance of annexin-A1, retinaldehyde dehydrogenase-1, and vinculin, compared with their non-diabetic counterparts. These proteins are involved in cytoskeleton function and structure, oxidative stress, inflammation and retinoid metabolism. The presence of diabetes influences the VAT abundance of several proteins. Hence, the proteins identified here could be considered candidate molecules in future studies addressing the role that VAT dysfunction plays in the development of type 2 diabetes., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Inflammatory markers are elevated in type 2 diabetic patients (DP) and may predict the development of type 2 diabetes. Our aims were to analyze differences in the expression of inflammatory and immunological molecules between DP and healthy subjects and to investigate whether glycemic control might prevent the overexpression of inflammatory markers in DP. Twenty-two DP with advanced atherosclerosis and eight healthy blood donors were included. DP were classified as well (HbA1c ≤ 6.5) or poorly controlled (HbA1c > 6.5). In "in vitro" studies, monocytes were exposed to low (5.5 mM) or high glucose (26 mM) concentrations in the absence or presence of insulin. Expression profiling of 14 inflammatory genes was analyzed using TLDA analysis. "In vivo" results show that monocytes from DP had increased levels of monocyte chemoattractant protein (MCP-1) and interleukin 6 (IL6) and lower levels of Toll-like receptor 2 (TLR2) mRNA than healthy subjects. Well-controlled DP had lower levels of IL-6 than poorly controlled DP, suggesting that glycemic control may prevent IL6 mRNA alterations associated with diabetes. "In vitro" results demonstrate that glucose directly and significantly induced MCP-1 and IL6 and reduced TLR2 mRNA expression. Insulin at high dose (100 IU/ml) dramatically enhanced the upregulatory effects of glucose on MCP-1 and IL-6 and reduced per se TLR2 mRNA expression. MCP-1, IL-6 and TLR2 are key inflammatory players altered in monocytes from type 2 DP. Both hyperinsulinemia and hyperglycemia contribute to alter the expression of these genes. The glycemic control only significantly prevented IL6 overexpression in this group of patients.

Background: Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD)., Methods: A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine samples., Results: Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes. Overall, a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors. The patients with known diabetes had a 2-fold higher odds of CKD or CVD. However, when both parameters were introduced in the same model, the HbA1c concentration was only significantly associated with clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of one percentage point was associated with a 30% to 40% increase in the rate of CKD or CVD. This relationship was apparent in persons with and without known diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population., Conclusion: HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population.

We present the first case of Raoultella planticola bacteria in human infections with a direct relationship between fish intake and enteric infection. The patient was treated with antibiotherapy (cefotaxime). It is important to consider this organism in the differential diagnosis of enteric fever and even more with previous ingestion of fish., (© 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Objective: Oxidized lipoproteins and antioxidized LDL antibodies (antioxLDL abs) have been detected in human plasma and atherosclerotic lesions. The principle aim of this study was to analyze the possible relationship between IgG and IgM antioxLDL abs and factors involved in different metabolic pathways (inflammation, lipid metabolism, apoptosis, and cell cycle arrest profile) in the occluded popliteal artery (OPA) compared with the femoral vein (FV)., Research Design and Methods: Fifteen patients with advanced atherosclerosis and type 2 diabetes undergoing lower limb amputation participated in this study. Each patient had OPA and FV biopsy specimens and peripheral arterial occlusive disease. By real-time PCR, gene expression was analyzed from the OPA and FV specimens, and antioxLDL ab levels were measured by specific enzyme-linked immunosorbent assay., Results: The OPA and FV showed a positive correlation between only IgM antioxLDL ab levels and the expression of genes involved in different metabolic pathways, including inflammation (TFPI), apoptosis (BAX, caspase 3, AKT1), plaque disruption (MMP2 and MMP10), lipid metabolism (SCARB1, PPARg), and cell turnover (CDKN1A), and genes for transcription and growth factors (NFkB and VEGFA, respectively)., Conclusions: The results show that gene expression in the metabolic pathways (apoptosis, lipid metabolism, and inflammation) in the OPA and FV are directly related to the levels of IgM antioxLDL abs.

Introduction: Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a rare, benign, autoimmune condition characterized by lymphadenopathy, fever and neutropenia. It is a self-limited condition of unknown etiology., Case Presentation: We report the case of a 45-year-old Caucasian man with the first known case of Kikuchi disease associated with dramatic weight loss after bariatric surgery., Conclusion: Although the association between Kikuchi disease and bariatric surgery may be entirely coincidental, we speculate whether the immune dysfunction associated with weight loss may have played an etiologic role in this process.

Aims: Vascular risk equations are tools used to help prevent cardiovascular events. Our aim was to compare the REGICOR and SCORE equations in a general population and in persons with the metabolic syndrome (MS) according to the criteria of the International Diabetes Federation., Methods and Results: We calculated the cardiovascular risk with both equations in a random sample of 838 non-diabetic persons aged 40-65years without a history of cardiovascular disease, of whom 251 had the MS. Of the 838 persons, 3.6% had a high risk according to SCORE and 1.5% according to REGICOR, and of these, 53.3% and 61.5%, respectively, had the MS. The mean risk was greater in the persons with the MS than those without (REGICOR 4.6% vs. 2.6% and SCORE 1.7% vs. 1%; p<0.01 for each). In comparison with the group without the MS, the percentage of persons with the MS who had a high risk was greater with both scales: REGICOR (3.2% vs. 0.8%, p=0.027) and SCORE (6.4% vs. 2.4%, p=0.004). The agreement (kappa index) classifying the subjects with a high risk, was 0.453 in the overall sample and 0.391 in the subgroup with the MS., Conclusions: The percentage of persons classified as having a high cardiovascular risk differed between REGICOR and SCORE. Using these scales only a small percentage of non-diabetic persons with the MS have a high risk. The presence of the MS multiplies the percentage of non-diabetic persons with a high vascular risk two-fold with SCORE and four-fold with REGICOR., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.