Inflammation and weight change related to neurocognitive and functional impairment in diabetes and psychiatric disorders.

INTRODUCTION: Obesity is a global pandemic associated with various cardio-metabolic and psychiatric disorders. Neurocognitive and functional deficits have been associated with several somatic and psychiatric disorders. Adiposity-related inflammation has recently emerged as a key risk factor for neurocognitive and functional impairments. This prospective transdiagnostic study aimed to investigate the role of adiposity-related inflammatory markers in neurocognitive and functional outcomes associated with weight changes. METHODS: Peripheral blood inflammatory and oxidative stress biomarkers and neurocognitive and functional performance were assessed twice over 1 year in 165 individuals, including 30 with schizophrenia, 42 with bipolar disorder, 35 with major depressive disorder, 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls. Participants were stratified by body mass index into categories of type 2 obesity (T2OB; n=30), type 1 obesity (T1OB; n=42), overweight (OW; n=53), and average weight (NW; n=40). Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. RESULTS: Compared with NW, T2OB and T1OB were significantly associated with impaired neurocognitive and functional performance (p<0.01; η2p=0.06-0.12) and higher levels of C-reactive protein and platelets (PLT) (p<0.01; η2p=0.08-0.16), with small-to-moderate effect sizes. IL-6, IL-10, and PLT were key factors for detecting significant weight changes in T1OB and T2OB over time. Regression models revealed that inflammatory and oxidative stress biomarkers and cellular adhesion molecules were significantly associated with neurocognitive and functional performance (p<0.05). DISCUSSION: Obesity is characterized by neurocognitive and functional impairments alongside low-grade systemic inflammation. Adiposity-related inflammatory biomarkers may contribute to neurocognitive and functional decline in individuals with T2DM and psychiatric disorders. Our data suggest that these biomarkers facilitate the identification of specific subgroups of individuals at higher risk of developing obesity.

Inflammation and lipid metabolism as potential biomarkers of memory impairment across type 2 diabetes mellitus and severe mental disorders.

INTRODUCTION: Neurocognitive impairment is a transdiagnostic feature across several psychiatric and cardiometabolic conditions. The relationship between inflammatory and lipid metabolism biomarkers and memory performance is not fully understood. This study aimed to identify peripheral biomarkers suitable to signal memory decline from a transdiagnostic and longitudinal perspective. METHODS: Peripheral blood biomarkers of inflammation, oxidative stress and lipid metabolism were assessed twice over a 1-year period in 165 individuals, including 30 with schizophrenia (SZ), 42 with bipolar disorder (BD), 35 with major depressive disorder (MDD), 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls (HCs). Participants were stratified by memory performance quartiles, taking as a reference their global memory score (GMS) at baseline, into categories of high memory (H; n = 40), medium to high memory (MH; n = 43), medium to low memory (ML; n = 38) and low memory (L; n = 44). Exploratory and confirmatory factorial analysis, mixed one-way analysis of covariance and discriminatory analyses were performed. RESULTS: L group was significantly associated with higher levels of tumor necrosis factor-alpha (TNF-α) and lower levels of apolipoprotein A1 (Apo-A1) compared to those from the MH and H groups (p < 0.05; η2p = 0.06-0.09), with small to moderate effect sizes. Moreover, the combination of interleukin-6 (IL-6), TNF-α, c-reactive protein (CRP), Apo-A1 and Apo-B compounded the transdiagnostic model that best discriminated between groups with different degrees of memory impairment (χ2 = 11.9-49.3, p < 0.05-0.0001). CONCLUSIONS: Inflammation and lipid metabolism seem to be associated with memory across T2DM and severe mental illnesses (SMI). A panel of biomarkers may be a useful approach to identify individuals at greater risk of neurocognitive impairment. These findings may have a potential translational utility for early intervention and advance precision medicine in these disorders.

Immune-Inflammatory Biomarkers Predict Cognition and Social Functioning in Patients With Type 2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A 1-Year Follow-Up Study.

Background: Systemic, low-grade immune-inflammatory activity, together with social and neurocognitive performance deficits are a transdiagnostic trait of people suffering from type 2 diabetes mellitus (T2DM) and severe mental illnesses (SMIs), such as schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to determine if immune-inflammatory mediators were significantly altered in people with SMIs or T2DM compared with healthy controls (HC) and whether these biomarkers could help predict their cognition and social functioning 1 year after assessment. Methods: We performed a prospective, 1-year follow-up cohort study with 165 participants at baseline (TB), including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 HC; and 125 at 1-year follow-up (TY), and determined executive domain (ED), global social functioning score (GSFS), and peripheral blood immune-inflammatory and oxidative stress biomarkers. Results: Participants with SMIs and T2DM showed increased peripheral levels of inflammatory markers, such as interleukin-10 (p < 0.01; η2 p = 0.07) and tumor necrosis factor-α (p < 0.05; η2 p = 0.08); and oxidative stress biomarkers, such as reactive oxygen species (ROS) (p < 0.05; η2 p = 0.07) and mitochondrial ROS (p < 0.01; η2 p = 0.08). The different combinations of the exposed biomarkers anticipated 46-57.3% of the total ED and 23.8-35.7% of GSFS for the participants with SMIs. Limitations: Participants' treatment, as usual, was continued without no specific interventions; thus, it was difficult to anticipate substantial changes related to the psychopharmacological pattern. Conclusion: People with SMIs show significantly increased levels of peripheral immune-inflammatory biomarkers, which may contribute to the neurocognitive and social deficits observed in SMIs, T2DM, and other diseases with systemic immune-inflammatory activation of chronic development. These parameters could help identify the subset of patients who could benefit from immune-inflammatory modulator strategies to ameliorate their functional outcomes.

Psychometric properties of a questionnaire to measure adherence to treatment in patients with type 1 diabetes mellitus.

AIM: To validate the psychometric properties of a questionnaire to measure adherence to treatment among people with type 1 diabetes mellitus and to evaluate its relationship with metabolic control. DESIGN: A cross-sectional study of 167 adult people with type 1 diabetes mellitus recruited from the Endocrinology Service of University Hospital Doctor Peset (Spain). METHODS: The validity of the content, construct and reliability of the instrument were evaluated and the results correlated with levels of glycosylated haemoglobin. RESULTS: The questionnaire was composed of 25 items and 5 dimensions, with a score of 25-150 points and an internal consistency of 0.92, according to Cronbach's coefficient α. The content of validity ratio and the construct (exploratory functional analysis, Kaiser-Meyer-Olkin index and Barlett's spherical test) were adequate. We observed a significant correlation between glycosylated haemoglobin levels and treatment adherence. CONCLUSION: The questionnaire to measure adherence to treatment in type 1 diabetes mellitus is consistent, reliable and valid, showing an excellent association with degree of metabolic control.

Specific metabolic syndrome components predict cognition and social functioning in people with type 2 diabetes mellitus and severe mental disorders.

OBJECTIVE: Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS components might be associated with neurocognitive and functional impairments in these individuals. The predictive and discriminatory validity of MetS and its components regarding those outcomes were assessed from prospective and transdiagnostic perspectives. METHODS: Metabolic syndrome components and neurocognitive and social functioning were assessed in 165 subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HCs). A posteriori, individuals were classified into two groups. The MetS group consisted of those who met at least three of the following criteria: abdominal obesity (AO), elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL), elevated blood pressure (BP), and elevated fasting glucose (FPG); the remaining participants comprised the No-MetS group. Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. RESULTS: Cognitive impairment was significantly greater in the MetS group (n = 82) than in the No-MetS group (n = 83), with small effect sizes (p < 0.05; η²p = 0.02 - 0.03). In both groups, the most robust associations between MetS components and neurocognitive and social functioning were observed with TG and FPG (p < 0.05). There was also evidence for a significant relationship between cognition and BP in the MetS group (p < 0.05). The combination of TG, FPG, elevated systolic BP and HDL best classified individuals with greater cognitive impairment (p < 0.001), and TG was the most accurate (p < 0.0001). CONCLUSIONS: Specific MetS components are significantly associated with cognitive impairment across somatic and psychiatric disorders. Our findings provide further evidence on the summative effect of MetS components to predict cognition and social functioning and allow the identification of individuals with worse outcomes. Transdiagnostic, lifestyle-based therapeutic interventions targeted at that group hold the potential to improve health outcomes.

Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study.

BACKGROUND: Neurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach. METHODS: A total of 165 participants, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning. RESULTS: Common neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01, η²p=0.08-0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; η²p=0.29-0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; η²p=0.13-0.43) and could accurately differentiate individuals with somatic and psychiatric disorders (χ² = 48.0, p < 0.0001). LIMITATIONS: The initial sample size was small, and high experimental mortality was observed after follow-up for one year. CONCLUSIONS: This longitudinal study provides evidence of some possible overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings open promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases.

Physicochemical Properties of Lipoproteins Assessed by Nuclear Magnetic Resonance as a Predictor of Premature Cardiovascular Disease. PRESARV-SEA Study.

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

Erratum: Bosch-Sierra, N., et al. Effect of Fibre-Enriched Orange Juice on Postprandial Glycaemic Response and Satiety in Healthy Individuals: An Acute, Randomised, Placebo-Controlled, Double-Blind, Crossover Study. Nutrients 2019, 11, 3014.

The authors have requested that the following changes be made to their paper [...].

Triglicéridos, colesterol HDL y dislipidemia aterogénica en la guía europea para el control de las dislipidemias 2019 / Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias

En general, las guías de práctica clínica tanto europeas con americanas han abordado el control de la dislipidemia aterogénica de forma poco convincente e incluso superficial, en gran medida por las limitaciones terapéuticas disponibles. En consecuencia, esta dislipidemia está infradiagnosticada, infratratada e infracontrolada. Dada la reciente aparición de la guía 2019 de la European Atherosclerosis Society y de la European Society of Cardiology sobre el control de las dislipidemias, parece oportuno examinar su posicionamiento con respecto a la dislipidemia aterogénica y/o sus principales componentes, el aumento en las lipoproteínas ricas en triglicéridos y la disminución del colesterol de las lipoproteínas de alta densidad

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol

Dislipidemia aterogénica 2019. Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis / Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society

No disponible

Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias. / Triglicéridos, colesterol HDL y dislipidemia aterogénica en la guía europea para el control de las dislipidemias 2019.

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol.

Malnutrition impairs mitochondrial function and leukocyte activation.

BACKGROUND: The aim of this study was to evaluate markers of inflammation, oxidative stress and endothelial function in a disease-related malnutrition (DRM) outpatient population. METHODS: For this cross-sectional study, a total of 83 subjects were included and clustered in 3 groups: 34 with normonutrition (NN), 21 with DRM without inflammation (DRM-I) and 28 with DRM and inflammation (DRM + I). Nutritional diagnosis was conducted for all subjects according to ASPEN. Biochemical parameters, proinflammatory cytokines, reactive oxygen species production, glutathione, mitochondrial membrane potential, oxygen consumption, adhesion molecules and leukocyte-endothelium interactions were evaluated. RESULTS: DRM + I patients showed lower albumin, prealbumin, transferrin, and retinol-binding protein levels with respect to the NN group (p < 0.05), differences that were less noticeable in the DRM-I group. DRM + I was associated with a significant increase in hsCRP and IL6 vs the NN and DRM-I groups, and TNFα was increased in both DRM vs NN. DRM was characterised by increased oxidative stress, which was marked by a significant increase in ROS levels and a decrease in mitochondrial membrane potential in the DRM + I group. An evident reduction in mitochondrial oxygen consumption and glutathione concentration was observed in both DRM groups, and was accompanied by increased leukocyte adhesion and adhesion molecules and decreased rolling velocity in the DRM + I group. Furthermore, percentage of weight loss was negatively correlated with albumin, prealbumin, transferrin, O2 consumption, glutathione and leukocyte rolling velocity, and positively correlated with hsCRP, IL6, TNFα, ROS, leukocyte adhesion, and VCAM-1. CONCLUSIONS: Our results show that DRM is associated with oxidative stress and an inflammatory state, with a deterioration of endothelial dysfunction in the DRM + I population.

Effect of Fibre-Enriched Orange Juice on Postprandial Glycaemic Response and Satiety in Healthy Individuals: An Acute, Randomised, Placebo-Controlled, Double-Blind, Crossover Study.

Background: Consumption of fibre-enriched orange juice may be an appropriate way to supplement daily fibre intake and achieve beneficial effects on metabolic health. The present study aimed to assess the short-term effects of fibre-enriched orange juice on postprandial metabolism and satiety in a healthy adult population. Methods: In this double-blind, randomised, placebo-controlled, crossover study 10 healthy subjects underwent two one-day trials in which they consumed an orange juice beverage containing 1.4 g/100 mL of citrus fibre (29.3% soluble and 41.9% insoluble) or a placebo (regular orange juice without added fibre). Postprandial glucose, insulin, gut hormones (GLP1, GIP and ghrelin), leptin and qualitative appetite/satiety assessment were measured every 15 or 30 min over the 120 min test period. Results: The fibre-enriched orange juice decreased postprandial serum glucose and circulating insulin levels at 15 min compared with the placebo. In addition, after intake of the fibre-enriched juice, a significant effect on qualitative feelings of satiety and fullness was observed at 15 and 120 min, and was accompanied by a significant decrease in GLP1 response at 15 min. No significant changes were observed in leptin, GIP and ghrelin after juice intake. Conclusions: In healthy individuals, a single acute consumption of fibre-enriched orange juice has short-term beneficial effects on postprandial glycaemia, circulating insulin levels and satiety through GLP1 secretion.

Non-HDL cholesterol as a therapeutic goal. / Colesterol-no HDL como objetivo terapéutico.

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30mg/dL to the c-LDL targets.

Colesterol-no HDL como objetivo terapéutico / Non-HDL cholesterol as a therapeutic goal

Aunque el colesterol unido a las lipoproteínas de baja densidad (c-LDL) está bien establecido como un factor de riesgo de las enfermedades cardiovasculares; existe frecuentemente un patrón dislipidémico más complejo que contribuye a la formación de la placa arteriosclerótica. El colesterol no HDL (c-NO-HDL) se utiliza para la estimación de la cantidad total de lipoproteínas aterogénicas en plasma, algunas de las cuales no son determinadas habitualmente en la práctica clínica diaria. El c-NO-HDL se calcula fácilmente a partir de la sustracción de la cifra de colesterol total plasmático el contenido de colesterol vehiculizado por las lipoproteínas de alta densidad. El c-NO-HDL presenta una superioridad predictora sobre el c-LDL para estimar el riesgo de eventos cardiovasculares mayores en los estudios epidemiológicos. Los estudios genéticos mediante análisis del genoma completo, junto a los basados en la aleatorización mendeliana, apuntan al carácter etiológico del c-NO-HDL sobre la cardiopatía isquémica (CI). Los estudios de intervención, y los metaanálisis de ellos derivados, cierran el círculo causal entre c-NO-HDL y CI al demostrar que cualquier intervención que haga disminuir las concentraciones del primero aminora la incidencia de la cardiopatía arteriosclerótica. La guía europea ESC/EAS 2016 para el manejo de las dislipidemias contempla al c-NO-HDL como una diana terapéutica con una recomendación clase iia (debería realizarse), nivel B (datos de un único RCT o de varios no RCT), y fija su objetivo en menor de 100 o 130 mg/dl para aquellos pacientes con muy alto riesgo o alto riesgo, respectivamente. Estos valores a lograr de c-NO-HDL se calculan fácilmente añadiendo 30 mg/dl a los objetivos c-LDL

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30 mg/dL to the c-LDL targets

The SGLT2 Inhibitor Empagliflozin Ameliorates the Inflammatory Profile in Type 2 Diabetic Patients and Promotes an Antioxidant Response in Leukocytes.

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to a considerable reduction in cardiovascular risk in patients with type 2 diabetes (T2D), but the precise molecular mechanisms are still elusive. We aimed to evaluate the effects of the iSGLT2 empagliflozin on systemic inflammation and its potential antioxidant properties. This is an observational, prospective follow-up study of a cohort of fifteen patients with T2D who received 10 mg/day of empagliflozin according to standard clinical care. Measures at baseline, 12 and 24 weeks were taken. Metabolic and anthropometric parameters were evaluated. Production of mitochondrial superoxide, glutathione content, and glutathione s-reductase and catalase mRNA levels were measured in leukocytes. Serum levels of myeloperoxidase, hs-CRP and IL-10 were determined. In addition to decreased body weight and reduced glucose and HbA1c levels, we observed a reduction in superoxide production in leukocytes of diabetic patients and increased glutathione content, prominently after 24 weeks of empagliflozin treatment. Leukocyte expression of glutathione s-reductase and catalase, and serum levels of IL-10 were enhanced at 24 weeks of empagliflozin treatment. Concomitantly, reduced hs-CRP and myeloperoxidase levels were seen. This study provides evidence of the antioxidant and anti-inflammatory properties of empagliflozin treatment in humans, which may contribute to its beneficial cardiovascular effects.

Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women.

Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin's effects on lipid metabolism, a crucial process in PCOS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with PCOS following metformin treatment. The aim is to offer new insights about the effect of metformin in PCOS patients. Plasma samples were obtained from 27 subjects prior to and following 12 weeks of metformin treatment. A detailed biochemical characterization and lipidomic profile was performed. Metformin reduces BMI, HOMA-IR, FSH and androstenedione and increases DHEA-S but no changes were found in glucose levels after treatment. Multivariate statistics revealed a specific lipidomic signature due to the effect of 12 weeks of metformin treatment in PCOS patients. This signature includes changes in sphingolipid metabolism suggesting a crosstalk between these lipid species and the androgenic metabolism and a decrease in oxidized lipids reinforcing that metformin treatment improves oxidative stress status. Our study confirms the specific effect of metformin in lipid metabolism on women with PCOS after 12 weeks of treatment.

Role of Endoplasmic Reticulum and Oxidative Stress Parameters in the Pathophysiology of Disease-Related Malnutrition in Leukocytes of an Outpatient Population.

Cellular pathways such as inflammation or oxidative stress are the cause and triggers of disease-related malnutrition (DRM), but the influence of these markers on endoplasmic reticulum (ER) stress is unknown. The objective of this study was to analyze the relationship between mitochondrial function and ER stress parameters in a DRM population. The study population was composed of 82 outpatient subjects, of whom 45 were diagnosed with DRM and 37 were confirmed to be normonourished according to the American Society for Parenteral and Enteral Nutrition ASPEN criteria. We evaluated anthropometrical and biochemical parameters, pro-inflammatory cytokines in serum. Oxidative and ER stress markers were analyzed in leukocytes. DRM patients showed significant reductions in albumin and transferrin concerning the normonourished group, and also displayed higher levels of hsCRP, IL6, and TNFα, and the soluble adhesion molecules VCAM-1 and ICAM-1. Besides, oxygen consumption and mitochondrial membrane potential were reduced and Radical Oxygen Species ROS production was enhanced in DRM patients. In the case of ER markers, protein and mRNA expression revealed that CHOP, ATF6, and the P-eIF2α signal were enhanced in malnourished patients compared to control subjects. Correlation studies supported a relationship between weight loss and increased inflammation, mitochondrial dysfunction, and compromised function of the ER. Our results demonstrate that ER stress signaling pathways are influenced by inflammation and mitochondrial function in the leukocytes of a DRM population.

Riesgo cardiovascular residual de origen lipídico. Componentes y aspectos fisiopatológicos / Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects

Es indudable la relación del cLDL y el riesgo cardiovascular, así como de los beneficios del tratamiento con estatinas. Una vez conseguido el objetivo de cLDL, son notables las evidencias que demuestran la persistencia de un elevado riesgo cardiovascular, concepto denominado riesgo residual. El riesgo residual de origen lipídico se fundamenta en la dislipidemia aterogénica, caracterizada por un aumento de triglicéridos y de las lipoproteínas ricas en triglicéridos, un descenso del cHDL y alteraciones cualitativas de las partículas LDL. Las medidas más utilizadas para identificar esta dislipidemia se basan en la determinación de colesterol total, triglicéridos, HDL, colesterol no HDL y colesterol remanente, además de las apolipoproteínas B100 y la lipoproteína(a) en determinados casos. El tratamiento de la dislipidemia aterogénica se basa en la pérdida de peso y ejercicio físico. En cuanto al tratamiento farmacológico, no tenemos evidencia del beneficio cardiovascular con los fármacos dirigidos al descenso de triglicéridos y cHDL; el fenofibrato parece tener eficacia en situaciones de dislipidemia aterogénica

There is no doubt about the relationship between LDL-c and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-c has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterized by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-c and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining cholesterol, as well as apolipoprotein B100 and lipoprotein (a) in certain cases. The treatment of atherogenic dyslipidemia is based on weight loss and physical exercise. Regarding pharmacological treatment, we have no evidence of cardiovascular benefit with drugs aimed at lowering triglycerides and HDL-c, fenofibrate seems to be effective in situations of atherogenic dyslipidemia