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.

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.

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.

The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic ß Cells Exposed to Hyperglycaemia.

BACKGROUND/AIMS: Mitochondria-targeted antioxidants such as mitoquinone (MitoQ) have demonstrated protective effects against oxidative damage in several diseases. The increase in reactive oxygen species (ROS) production during glucose metabolism in ß cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to ß cell function impairment. In the present work, we aimed to evaluate the effect of MitoQ on insulin secretion, oxidative stress, endoplasmic reticulum (ER) stress and nuclear factor kappa B (NFκB) signalling in a pancreatic ß cell line under normoglycaemic (NG, 11.1 mM glucose), hyperglycaemic (HG, 25 mM glucose) and lipidic (palmitic acid (PA), 0.5mM) conditions. METHODS: We incubated the pancreatic ß cell line INS-1E with or without MitoQ (0.5µM) under NG, HG and PA conditions. We then assessed the following parameters: glucose-induced insulin secretion, O2 consumption (with a Clark-type electrode); mitochondrial function, oxidative stress parameters and calcium levels (by fluorescence microscopy); ER stress markers and NFκB-p65 protein levels (by western blotting). RESULTS: MitoQ increased insulin secretion and prevented the enhancement of ROS production and O2 consumption and decrease in GSH levels that are characteristic under HG conditions. MitoQ also reduced protein levels of ER stress markers (GRP78 and P-eIF2α) and the proinflammatory nuclear transcription factor NFκB-p65, both of which increased under HG. MitoQ did not significantly alter ER stress markers under lipidic conditions. CONCLUSION: Our findings suggest that treatment with MitoQ modulates mitochondrial function, which in turn ameliorates endoplasmic reticulum stress and NFκB activation, thereby representing potential benefits for pancreatic ß cell function.

Dietary therapy and non-surgical periodontal treatment in obese patients with chronic periodontitis.

AIM: The effect of dietary weight loss intervention on periodontal therapy is unknown. Therefore, we aimed to evaluate whether weight loss improves the response of obese subjects to non-surgical periodontal treatment. MATERIALS AND METHODS: This interventional study in obese patients was conducted at the University Hospital Dr. Peset (Valencia, Spain). Patients were divided into two groups with and without dietary therapy. All participants received non-surgical periodontal treatment. Periodontal, anthropometric and biochemical parameters were assessed at baseline and 12 weeks. RESULTS: A total of 78 patients were re-evaluated after intervention. All periodontal parameters improved in both groups after periodontal treatment, but the reductions in mean probing depth (PD) (0.23 mm vs. 0.12 mm) and in percentage of sites with PD 4-5 mm (10.4% vs. 5.89%) were significantly higher in the dietary group. Additionally, complement component 3 (C3) and tumour necrosis factor alpha (TNFα) decreased in the dietary group after intervention. Percentage of change in mean PD correlated with change in C3 (r = 0.233, p = 0.043), and percentage of change in sites with PD 4-5 mm correlated with change in TNFα (r = 0.414, p = 0.012). CONCLUSIONS: This study suggests that dietary weight loss intervention causes a greater reduction in systemic inflammation, which may enhance the response to periodontal treatment.

[Validation of nutritional screening Malnutrition Screening Tool compared to other screening tools and the nutritional assessment in different social and health areas]. / Validación del cribado nutricional Malnutrition Screening Tool comparado con la valoración nutricional completa y otros cribados en distintos ámbitos sociosanitarios.

INTRODUCTION: nutritional screenings are used to detect nutritional risk, allow early intervention and influence the prognosis. The Malnutrition Screening Tool (MST) is only validated in hospitalized patients and oncology outpatients. OBJECTIVES: to analyze the nutritional screening MST, Malnutrition Universal Screening Tool (MUST) and Mini Nutritional Assessment-Short Form (MNA-sf) compared to the nutritional assessment gold standard according to socio-sanitary areas and age groups; and to assess the utility of the MST in those areas where it has not been validated. MATERIAL AND METHODS: a total of 815 outpatient, hospitalized and institutionalized subjects were included in this study. MUST and MST screenings, and nutritional assessment were performed in all subjects. MNA-sf was also performed in subjects ≥ 65 years of age. Nutritional diagnosis was performed according to the SENPE-SEDOM consensus. RESULTS: in the outpatient cohort, three screenings have a validity (AUC ROC) greater than 0.8 compared to nutritional assessment. In the institutionalized, the MNA-sf generates false positives and the MUST is more valid than MST (AUC ROC = 0.815 and 0.763, respectively). In hospitalized patients, there are excellent results with MUST and MST. In all socio-sanitary areas the MST obtains a better positive predictive value. By age groups, MUST and MST are valid tools. CONCLUSIONS: in our study, the MST correctly diagnoses more than 80% of the patients (S = 69.4%, E = 94.2%), and has a good reliability and validity with respect to nutritional assessment not only in hospitalized patients and oncology outpatients, where it has already been validated. In our population, the MST was found to be valid in outpatient, institutionalized and hospitalized subjects.

Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome.

PURPOSE: In this work, a non-targeted approach was used to unravel changes in the plasma lipidome of PCOS patients. The aim is to offer new insights in PCOS patients strictly selected in order to avoid confounding factors such as dyslipemia, obesity, altered glucose/insulin metabolism, cardiovascular disease, or cancer. RESULTS: Multivariate statistics revealed a specific lipidomic signature for PCOS patients without associated pathologies. This signature implies changes, mainly by down-regulation, in glycerolipid, glycerophospholipid and sphingolipid metabolism suggesting an altered biosynthetic pathway of glycerophospholipids and cell signaling as second messengers in women with PCOS. CONCLUSIONS: Our study confirms that a lipidomic approach discriminates a specific phenotype from PCOS women without associated pathologies from healthy controls. METHODS: In a cross-sectional pilot study, data were obtained from 34 subjects, allocated to one of two groups: a) lean, healthy controls (n = 20), b) PCOS patients (n = 14) with diagnosis based on hyperandrogenaemia, oligo-anovulation and abnormal ovaries with small follicular cysts. A detailed biochemical characterization was made and lipidomic profiling was performed via an untargeted approach using LC-ESI-QTOF MS/MS.

Pinitol alleviates systemic inflammatory cytokines in human obesity by a mechanism involving unfolded protein response and sirtuin 1.

BACKGROUND & AIMS: It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). METHODS: In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo study, a biopsy of VAT and SAT was removed from thirty-four obese patients and incubated with D-pinitol for 48 h. RESULTS: The consumption of a PEB reduced circulating levels of IL6 and TNFα and increased SIRT1 protein expression in PBMCs. Ex vivo experiments showed a decline in gene expression and protein levels of IL6 and TNFα in SAT and a reduction in ER stress parameters (ATF6 and CHOP), while VAT markers remained unaltered. Differential gene expression profiles revealed an up-regulation of SIRT1 and insulin-signaling pathways in SAT with respect to VAT. CONCLUSIONS: Our results suggests that pinitol down-regulates the inflammatory pathway which may lead to novel treatment options for obesity and its metabolic disorders.

Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions. MATERIAL AND METHODS: This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endothelium interactions, adhesion molecules (VCAM-1, ICAM-1, E-Selectin), TNF-α and IL-6 were determined. RESULTS: Total ROS, inflammatory parameters and adhesion molecules were enhanced in the presence of MetS (p<0.05), and the PCOS+MetS group showed higher levels of IL-6 and ICAM-1 than controls (p<0.05). Increased adhesion and leukocyte rolling flux were observed in PCOS and PCOS+MetS groups vs their respective controls (p<0.05). GRP78 protein expression was higher in the PCOS groups (p<0.05 vs controls) and sXBP1 was associated with the presence of MetS (p<0.05 vs controls without MetS). Furthermore, PCOS+MetS patients exhibited higher GRP78 and ATF6 levels than controls and PCOS patients without MetS (p<0.05). In PCOS women, HOMA-IR was positively correlated with ICAM-1 (r=0.501; p<0.01), ROS (r=0.604; p<0.01), rolling flux (r=0.455;p<0.05) and GRP78 (r=0.574; p<0.001). CONCLUSION: Our findings support the hypothesis of an association between altered metabolic status, increased ROS production, ER stress and leukocyte-endothelium interactions in PCOS, all of which are related to vascular complications.

Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications.

Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF). PARKIN and (PTEN)-induced putative kinase 1 (PINK1) participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1), dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico.

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (I). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular.

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease.

The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients.

It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA-IR, HbA1c, triglycerides, hs-CRP and lower HDL-c with respect to controls. Mitochondrial ROS production was enhanced in T2D patients and decreased by MitoQ. The antioxidant also increased GPX-1 levels and PMN rolling velocity and decreased PMN rolling flux and PMN adhesion in T2D patients. NFκB-p65 and TNFα were augmented in T2D and were both reduced by MitoQ treatment. Our findings support that the antioxidant MitoQ has an anti-inflammatory and antioxidant action in the leukocytes of T2D patients by decreasing ROS production, leukocyte-endothelium interactions and TNFα through the action of NFκB. These data suggest that mitochondria-targeted antioxidants such as MitoQ should be investigated as a novel means of preventing cardiovascular events in T2D patients.

Short- and Long-Term Effects of Weight Loss on the Complement Component C3 After Laparoscopic Gastric Bypass in Obese Patients.

BACKGROUND: The C3 complement component (C3c) is increasingly recognized as a cardiometabolic risk factor, but how it is affected after weight loss through gastric bypass is a question yet to be answered. METHODS: A total of 66 obese patients underwent laparoscopic gastric bypass. Anthropometric parameters, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), glucose, insulin, HOMA-IR, liver enzymes, high-sensitivity C-reactive protein (hsCRP), and C3c levels were evaluated at baseline and at 1 and 5 years post-surgery. RESULTS: All anthropometric and biochemical parameters improved significantly after surgery, although a deterioration was detected with respect to the percentage of excess of weight loss, insulin, TC, LDLc, and lactate dehydrogenase 5 years post-surgery. Despite this, a remission rate of 84 % was observed in the presence of metabolic syndrome after 5 years follow-up. hsCRP and C3c were reduced significantly after surgery and maintained throughout the experimental period. In addition, C3c was correlated with BMI and insulin at all time points. The multivariate regression model, in which C3c was a dependent variable, revealed that aspartate aminotransferase and BMI were independent variables at baseline, alkaline phosphatase and insulin were independent at 1 year post-surgery, and insulin, BMI, and TC were independent at 5 years post-surgery. CONCLUSIONS: C3c may be a marker of the chronic inflammatory process underlying insulin resistance. Its association with BMI and liver enzymes supports a major role in metabolic activity, although future research is needed to clarify the nature of the molecular mechanisms involved and the physiological significance of these findings.

Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase.

Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial.

BACKGROUND & AIMS: Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. METHODS: A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23 g of inositols in 250 ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. RESULTS: Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24 h after consumption of the IEB. CONCLUSIONS: Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance.

OBJECTIVE: Oxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα). DESIGN AND METHODS: Our study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (n=41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O2 consumption (using a Clark-type O2 electrode), membrane potential, mitochondrial mass, and levels of reactive oxygen species (ROS) and glutathione (GSH) (by means of fluorescence microscopy) were assessed in poymorphonuclear cells. H2O2 was evaluated with the Amplex Red(R) H2O2/Peroxidase Assay kit. IL6 and TNFα were measured using the Luminex 200 flow analyser system. RESULTS: Metformin had beneficial effects on patients by increasing mitochondrial O2 consumption, membrane potential, mitochondrial mass and glutathione levels, and by decreasing levels of reactive oxygen species and H2O2. In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFα levels and increased dehydroepiandrosterone sulfate levels. HOMA-IR and mitochondrial function biomarkers positively correlated with ROS production (r=0.486, P=0.025), GSH content (r=0.710, P=0.049) and H2O2 (r=0.837, P=0.010), and negatively correlated with membrane potential (r=-0.829, P=0.011) at baseline. These differences disappeared after metformin treatment. CONCLUSIONS: Our results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.

Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients.

OBJECTIVE: We aim to assess the effect of metformin treatment on metabolic parameters, endothelial function and inflammatory markers in polycystic ovary syndrome (PCOS) subjects. METHODS: The study population consisted of 40 reproductive-age women with PCOS, who underwent treatment with metformin during a 12-week period, and their corresponding matched controls (n = 44). We evaluated endocrinological parameters, adhesion molecules (vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1) and E-selectin) and proinflammatory cytokines (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα)) in serum. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear (PMN) cells were assessed by flow chamber microscopy. In addition, a group of type 2 diabetes patients who underwent treatment with metformin during a 12-week period was incorporated into the study. RESULTS: Metformin produced beneficial effects on PCOS patients by decreasing polymorphonuclear (PMN) rolling flux and adhesion. It also decreased levels of ICAM-1, E-selectin, IL-6 and ΤΝFα. In addition, metformin induced an improvement of endocrine and anthropometric parameters in PCOS subjects by reducing glucose, follicle-stimulating hormone (FSH) and androstendione, and by increasing dehydroepiandrosterone-sulfate (DHEA-S). Metformin also had beneficial effects in type 2 diabetic subjects by reducing body weight, waist circumference and PMN adhesion, and by increasing PMN rolling velocity. CONCLUSION: Our results highlight the modulating effect of metformin on leukocyte/endothelium interactions. These findings may explain the potential beneficial effect of metformin in reducing the risk of vascular events in PCOS patients and in insulin resistance conditions.

Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.

BACKGROUND: Anorexia nervosa is a common psychiatric disorder in adolescence and is related to cardiovascular complications. Our aim was to study the effect of anorexia nervosa on metabolic parameters, leucocyte-endothelium interactions, adhesion molecules and proinflammatory cytokines. MATERIALS AND METHODS: This multicentre, cross-sectional, case-control study employed a population of 24 anorexic female patients and 36 controls. We evaluated anthropometric and metabolic parameters, interactions between leucocytes polymorphonuclear neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC), proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and soluble cellular adhesion molecules (CAMs) including E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Anorexia nervosa was related to a decrease in weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin and HOMA-IR, and an increase in HDL cholesterol. These effects disappeared after adjusting for BMI. Anorexia nervosa induced a decrease in PMN rolling velocity and an increase in PMN rolling flux and PMN adhesion. Increases in IL-6 and TNF-α and adhesion molecule VCAM-1 were also observed. CONCLUSIONS: This study supports the hypothesis of an association between anorexia nervosa, inflammation and the induction of leucocyte-endothelium interactions. These findings may explain, in part at least, the increased risk of vascular disease among patients with anorexia nervosa.