Nutritional factors and metabolic biomarkers: impact in risk and survival of women with breast cancer / Fatores nutricionais e biomarcadores metabólicos: impacto no risco e sobrevida de mulheres com câncer de mama

Breast cancer (BC) is the most common cause of cancer and the leading cause of death in women. BC is a complex disease and distributes in distinct molecular subtypes regarding the expression of estrogen receptor (ER), progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (HER2), and Ki67 protein status. Although BC is multifactorial evidence indicates that nutritional factors are relevant during steps of carcinogenesis, recurrence, and survival. We aim to assess the role of nutrition status and metabolic biomarkers in women with BC. This is a case-control study between May 2011 and August 2012. In the case group, there was a follow-up until April 2019, characterizing a cohort study. From these groups, different manuscripts were structured with different study designs according to each hypothesis. Manuscript 1 - cohort based on the follow-up of the BC group, Manuscript 2 - a cross-sectional study with women with Luminal A BC (ER positive, PR positive/negative, HER2 negative, Ki67 low) and Manuscript 3 - a cross-sectional case-control study. Data were obtained by medical records, interviews and anthropometric parameters with electrical impedance. Blood samples were collected after 12-hour fasting to analyze serum glucose, glycated hemoglobin, insulin growth factor 1 (IGF-1), insulin growth factor binding protein (IGFBP-3), insulin and adipokines, thiobarbituric acid reactive substances (TBARS), non-esterified fatty acids (NEFA), DNA oxidative damage (8-OH-dG) and lipoproteins (total cholesterol - TC, Low-density lipoprotein cholesterol - LDL-c, high-density lipoprotein cholesterol - HDL-c and triacylglycerols) and fatty acid profile of erythrocyte membrane. All statistical tests were performed using Statistical Package for Social Sciences® (SPSS), version 21.0. Statistical significance was set at p < 0.050. The main results of the study showed that premenopausal women with BC and clinical staging (CS) between II and III had a more atherogenic lipid profile characterized by the decrease in HDL-c, increase in LDL-c, non-HDL-C and apolipoprotein B (Apo B). We highlight that women with BC and high LDL-c and non-HDL-c had increase odd of having larger tumor size whereas HDL-c was associated with a decreased risk. Premenopausal women with BC had an increased level of TBARS and NEFA at diagnosis and had a lower survival probability. Additionally, women with Luminal A BC had higher serum levels of glucose, IGF-1, IGFBP-3, IL1ß, IL6, and lower IL10 compared to its matching controls. Also, women with increased serum levels of TBARS, glucose, and insulin increased risk of Luminal A BC, and higher levels of adiponectin decrease the risk of developing Luminal A BC when controlled by menopause status and BMI. Women with BC presented impaired IGF-1/insulin axis, sustained by overweight/obesity and higher central adiposity. Increased levels of serum glucose, insulin, and IGF-1 showed higher odds to developing BC. In conclusion, our results demonstrate the relevant impact of metabolic biomarkers on risk of developing BC and in survival outcomes. This study reinforces the relevance to increase prevention strategies regarding lifestyle and nutrition to decrease incidence and improve outcome of BC.

Câncer de mama (CM) é a causa mais comum de câncer no mundo e a principal causa de morte em mulheres. O CM é uma doença complexa e é classificada em tipos moleculares de acordo com a expressão do receptor de estrogênio (RE), receptor de progesterona (RP), receptor tyrosine-protein kinase erbB-2 (HER2) e proteína Ki67. Embora o CM seja multifatorial, há evidências científicas que indicam que componentes nutricionais podem ser relevantes durante as diversas etapas da carcinogênese, recidiva e sobrevivência. O objetivo deste estudo foi avaliar o papel do estado nutricional e marcadores metabólicos em mulheres com CM. Trata-se de um estudo caso-controle realizado entre maio 2011 e agosto 2012. O grupo caso foi acompanhado até abril 2019, caracterizando um estudo de coorte. A partir destes grupos foram estruturados diversos manuscritos com delineamentos diferentes, segundo cada hipótese levantada, a saber: Manuscrito 1 - Coorte baseada no seguimento do grupo CM, Manuscrito 2 - Estudo transversal baseado em mulheres com CM Luminal A (RE positivo, RP positivo/negativo, HER2 negativo, Ki67 baixo) e; Manuscrito 3 - estudo transversal do tipo caso-controle. Os dados foram obtidos através de prontuários médicos, entrevista e avaliação antropométrica com uso de bioimpedância elétrica. As amostras de sangue foram coletadas após jejum de 12 horas e a partir dessas foram analisadas glicemia, hemoglobina glicada (HbA1c), insulina, fator de crescimento semelhante à insulina 1 (IGF-1), proteína 3 de ligação ao fator de crescimento semelhante a insulina (IGFBP-3), substâncias reativas ao ácido tiobarbitúrico (TBARS), ácidos graxos não esterificados (NEFA), dano oxidativo ao DNA (8-OH-dG), perfil lipídico (colesterol total - CT, colesterol associado à lipoproteína de baixa densidade - LDL-c, colesterol associado à lipoproteína de alta densidade - HDL-c e triacilgliceróis) e perfil de ácidos graxos incorporados às membranas eritrocitárias. Todos os testes estatísticos foram realizados no programa Statistical Package for Social Sciences® (SPSS), versão 21.0. Significância estatística foi considerada em p < 0,050. Os principais resultados do estudo mostram que mulheres com CM na pré-menopausa e com estadiamento clínico II e III tiveram um perfil lipídico mais aterogênico caracterizado pela diminuição do HDL-c, aumento do LDL-c, nãoHDL-c e apolipoproteína B (Apo B). Destaca-se que mulheres com CM e LDL-c e nãoHDL-c aumentados apresentaram maior chance de tumores maiores, enquanto mulheres com CM com maior HDL-c apresentaram menor risco. Mulheres com CM na pré-menopausa que apresentaram maior conteúdo de TBARS e NEFA no momento do diagnóstico tiveram menor sobrevida. Adicionalmente, mulheres com CM e tumores do tipo Luminal A tiveram maiores concentrações de glicose, IGF-1, IGFBP-3, IL1ß, IL6 e menores de IL10 comparadas com o grupo controle. Mulheres com com concentrações mais elevadas de TBARS, glicose e insulina apresentaram maior risco de CM Luminal A, enquanto aquelas com concentrações mais elevadas de adiponectina apresentaram menor risco de desenvolver CM Luminal A, mesmo quando controlados pelo estado de menopausa e IMC. Mulheres com CM apresentaram alterações no eixo IGF-1/insulina que foi sustentada no sobrepeso/obesidade e no aumento da adiposidade central. Observou-se que mulheres com concentrações mais elevadas de glicose, insulina e IGF-1 tiveram maior chance de desenvolver CM. Em conclusão, os resultados demonstram o relevante impacto dos marcadores metabólicos no risco de desenvolver CM e o seu impacto na sobrevida. Este estudo reforça a relevância das estratégias de prevenção relacionadas ao estilo de vida e nutrição a fim de diminuir incidência e melhorar a sobrevida de mulheres com CM.

Blood glucose related adverse drug reaction of antitumor monoclonal antibodies: a retrospective analysis using Vigibase

Abstract On the increasing prevalence of using mAbs (monoclonal antibodies) in cancer therapy and the severe risk of hyperglycemia, we aimed to analyze the main clinical ADRs of mAbs, with a focus on adverse hyperglycemic events associated with currently clinically used mAbs. mAbs as well as target information were selected from Martinadale book and published articles. Drug approving information was collected from each government website, and ADR statistic data were collected from VigibaseR, comparing with Adverse Event Reporting System of US FDA. Top 10 mAbs were classified within listing in total ADR records, ADRs per year, hyperglycemic ADR records. Vigibase data were updated onto 15 Feb 2019. 20 mAbs were analyzed with 263217 ADR reports, wherein 16751 records on Metabolism and nutrition disorders and 1444 records on Glucose metabolism disorders. The geographic, age, gender distributions and annual ADR report numbers were listed respectively. Of the top 10, Rituximab, Bevacizumab and Nivolumab were on the top 3 in total ADR record and hyperglycemic record. Top 3 record results were similar in Vigibase and FDA database. It is of increasing importance for clinicians to be aware of early detection, patient management, or drug selection strategies when using mAbs, particularly within the high glycemic risk-reported mAbs, to improve the efficacy and tolerability of mAbs regiment and optimize patient outcomes.

Associations between vitamin D levels and glucose metabolism markers among pregnant women and their infants in Puerto Rico.

INTRODUCTION: Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/obesity (n = 31) and their infants at birth and 4 months. Results: insulin and HOMA-IR levels were higher among women with vitamin D below adequate levels compared to those with adequate levels in pregnancy (p < 0.05). Late in pregnancy, as vitamin D increased by one unit (ng/mL), insulin decreased by 0.44 units and HOMA-IR by 0.09 units. Maternal vitamin D late in pregnancy was correlated with infant vitamin D levels at birth (r = 0.89; p < 0.01) and 4 months (r = 0.9; p = 0.04), and with glucose (r = 0.79; p = 0.03) and insulin (r = 0.83; p = 0.04) at 4 months. Conclusion: maternal vitamin D status was associated with maternal and infant glucose metabolism in this sample.

INTRODUCCIÓN: Objetivos: un bajo nivel de vitamina D durante el embarazo es común y puede tener consecuencias adversas en la salud. Este estudio evaluó el nivel de vitamina D en mujeres embarazadas y sus bebés, así como su asociación con los marcadores de glucosa. Métodos: los niveles séricos de 25(OH)D, glucosa e insulina se midieron longitudinalmente en mujeres embarazadas hispanoamericanas con sobrepeso/obesidad (n = 31) y en sus bebés, desde el nacimiento hasta los 4 meses de edad, en Puerto Rico. Resultados: los niveles maternos de insulina y HOMA-IR eran mayores en las mujeres con niveles de vitamina D por debajo de lo considerado adecuado, comparado con aquellas con niveles adecuados durante todo el embarazo (p < 0,05). Al final del embarazo, a medida que los niveles de vitamina D aumentaron, por cada unidad (ng/mL) de aumento, la insulina disminuyo en 0,44 unidades y el HOMA-IR en 0,09 unidades. El nivel de vitamina D al final del embarazo se correlacionó con los niveles del bebé al nacer (r = 0,89; p < 0,01) y a los 4 meses (r = 0,9; p = 0,04), y con los niveles de glucosa (r = 0,79; p = 0,03) e insulina (r = 0,83; p = 0,04) a los 4 meses. Conclusión: el nivel materno de vitamina D se asoció con los marcadores maternos e infantiles de glucosa en esta muestra.

Repercussões metabólicas: quais, como e por que investigar? / Metabolic repercussions: which ones, how and why investigate?

A síndrome dos ovários policísticos (SOP) é frequentemente acompanhada de distúrbio metabólico, principalmente dos carboidratos e dos lipídeos, aumentando o risco de síndrome metabólica. Por essa razão, alguns investigadores ainda denominam a SOP de síndrome metabólica-reprodutiva. O objetivo deste capítulo é descrever as principais repercussões metabólicas, bem como como investigá-las e saber como suas consequências podem ser deletérias para a saúde da mulher. Esta é uma revisão narrativa mostrando a implicação do metabolismo dos carboidratos e dos lipídeos nas dislipidemias, bem como da síndrome metabólica sobre o sistema reprodutor, e o risco cardiovascular da mulher com SOP. Conclui-se que o manejo adequado dos distúrbios metabólicos na SOP é benéfico a curto e a longo prazo tanto para o sistema reprodutor quanto para o cardiovascular.(AU)

A Metabolically Unhealthy Phenotype Is Associated with ADIPOQ Genetic Variants and Lower Serum Adiponectin Levels.

BACKGROUND: Even though excessive adipose tissue is related to chronic metabolic disturbances, not all subjects with excess weight (EW) display metabolic alterations, and not all normal-weight (NW) subjects have a metabolically healthy (MH) phenotype, probably due to gene-environment interactions. The aim of this study was to investigate the interaction effects of ADIPOQ and PPARG genetic variants in NW and EW individuals with different metabolic phenotypes. METHODS: Data on 345 adults from western Mexico were analyzed. The individuals were classified into NW and EW groups according to body mass index, and were categorized as MH or metabolically unhealthy (MUH), considering homeostatic model assessment insulin resistance (HOMA-IR) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) cut-off points for glucose, triglycerides, high-density lipoprotein cholesterol, and blood pressure. Subjects with ≤1 altered parameter were classified as MH. The single nucleotide polymorphisms (SNPs) -11377C>G, -11391G>A, +45T>G, and +276G>T for ADIPOQ and Pro12Ala for PPARG were analyzed by allelic discrimination. High-molecular-weight adiponectin isoform levels were measured by ELISA. RESULTS: Lower serum adiponectin levels were associated with the MUH phenotype in EW subjects. NW subjects with the GG or TG genotype for the +45T>G SNP had reduced odds of the MUH phenotype. Individuals who carried two copies of the GG haplotype at the -11391G>A and -11377C>G SNPs for ADIPOQ had lower serum adiponectin levels than those with zero copies. CONCLUSION: In this population, lower serum adiponectin levels were found in the EW-MUH phenotype, and no differences were observed between the NW-MH and the EW-MH phenotype. In addition, the +45T>G SNP was associated with reduced odds of the MUH phenotype.

The triglyceride and glucose index is a useful biomarker to recognize glucose disorders in apparently healthy children and adolescents.

It has been suggested that the triglyceride and glucose (TyG) index is an early indicator for type 2 diabetes (T2D) in adults. Thus, the aim of this study was to evaluate whether the TyG index is useful in the screening of glucose disorders (GD) in apparently healthy children and adolescents. Eligible participants were apparently healthy children and adolescents. Individuals with new diagnosis of GD were allocated into the study groups with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and T2D. Participants with normal glucose tolerance (NGT) were the control group. In total, 1872 children and adolescents were enrolled and allocated into the study groups. Diagnosis of NGT, IFG, IGT, and T2D was established in 1541 (82.3%), 256 (13.7%), 66 (3.5%), and 9 (0.4%) children, respectively. In girls, the best cutoff points of the TyG index for identifying IFG, IGT, and T2D were 4.51 (sensitivity 59.8%, specificity 59.8%), 4.55 (sensitivity 63.0%, specificity 64.3%), and 4.63 (sensitivity 75.0%, specificity 74.6%), respectively; and in boys were 4.52 (sensitivity 62.8%, specificity 64.2%), 4.54 (sensitivity 71.8%, specificity 65.1%), and 4.82 (sensitivity 91.0%, specificity 990.6%), respectively.Conclusion: Our results suggest that the TyG index may be a useful tool for screening GD in healthy children and adolescents.What is Known:• Prevalence of prediabetes and type 2 diabetes is increasing worldwide among young adults and adolescents.• Elevated fasting glucose and triglyceride concentrations have been recognized as independent risk factors for type 2 diabetes.What is New:• The TyG index exhibited highest sensitivity and specificity to detect impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes.• The TyG index may be a useful tool for the screening of glucose disorders in apparently healthy children and adolescents.

Use of an Extract of Annona muricata Linn to Prevent High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice.

Annona muricata Linn, commonly known as graviola, is one of the most popular plants used in Brazil for weight loss. The aim of this study is to evaluate the therapeutic effects of three different doses (50 mg/kg, 100 mg/kg, and 150 mg/kg) of aqueous graviola leaf extract (AGE) supplemented by oral gavage, on obese C57BL/6 mice. Food intake, body weight, an oral glucose tolerance test (OGTT), an insulin sensitivity test, quantification of adipose tissue cytokines, weight of fat pads, and serum biochemical and histological analyses of the liver, pancreas, and epididymal adipose tissue were measured. AGE had an anti-inflammatory effect by increasing IL-10 at doses of 50 and 100 mg/kg. Regarding the cholesterol profile, there was a significant decrease in LDL-cholesterol levels in the AGE 150 group, and VLDL-cholesterol and triglycerides in the AGE 100 and 150 groups. There was an increase in HDL cholesterol in the AGE 150 group. The extract was able to reduce the adipocyte area of the epididymal adipose tissue in the AGE 100 and 150 groups. According to the histological analysis of the liver and pancreas, no significant difference was found among the groups. There were no significant effects of AGE on OGTT and serum fasting glucose concentration. However, the extract was effective in improving glucose tolerance in the AGE 150 group.

The fat-to-lean mass ratio, a novel anthropometric index, is associated to glucose metabolic disorders.

OBJECTIVE: The aim was to evaluate whether the Fat-to-Lean Mass (FyM) ratio is associated to glucose metabolic disorders (GMD). DESIGN: Cross-sectional population based study. METHODS: Eligible subjects were healthy men and non-pregnant women with new diagnosis of GMD that were allocated into following groups: 1) Normal Glucose Tolerance (NGT), 2) Diabetes, 3) impaired fasting glucose (IFG) + impaired glucose tolerance (IGT), 4) IGT, and 5) IFG. The FyM index [Total body fat (Kg)/total lean mass (Kg)], and the odds ratio (OR) between FyM index and GMD were estimated. RESULTS: A total of 875 individuals with average age 41.62 ±â€¯12.3 were enrolled; of them, 645 (73.1%) women and 230 (22.8%) men; 521 (59.5%), 71 (8.1%), 85 (9.7%), 53 (6.0%), and 145 (16.6%) individuals were allocated into groups with NGT, diabetes, IFG + IGT, IGT, and IFG, respectively. The FyM was significantly associated with prediabetes and diabetes in women (OR 4.2; 95%CI 3.0-11.1 and OR = 7.2; 95%CI 2.0-15.2) and men (OR = 2.6; 95%CI 1.1-6.7 and OR = 4.6; 95%CI 1.4-15.1). In the overall population, the OR between FyM index with IGT, IFG, and IFG + IGT was 8.4 (95%CI 2.6-17.4), 5.2 (95%CI 2.6-10.6), and 6.1 (95%CI 1.8-9.5). CONCLUSION: The FyM index was strongly associated with all categories of GMD.

Prediabetic state and dyslipidemia in freshmen in Health Sciences campus of a Mexican University / Prediabetes y dislipidemia en estudiantes de Nuevo ingreso al campus de Ciencias de la Salud de una universidad Mexicana

Objective: given the dramatic increase of diabetes in the world, the objective of this research was to analyze the values of blood glucose in a university population again income to support strategies for detection and preventive management of pre-diabetes and diabetes. Materials and methods: this is an observational, analytical,cross-sectional, non-probabilistic study to analyze biochemical markers in two freshman populations in a School of Medicine, 367 students enrolled in 2011 and 430 enrolled in 2016. The study variables were glycemia, triglyceridemia, and cholesterolemia.Statistical measures of central tendency, dispersions, and correlations for the groups,and applied Chi-square to clinical categories was analiced. Results: it was found significant increases in women in glycemia between 2011 and 2016: t = -4.582 (p = 0.0001) and cholesterolemia t = -9.124 (p = 0.0001). Men had significant increases in glycemia with t = -6.428 (p = 0.0001) and cholesterolemia with t = -9.499 (p = 0.0001).There was a higher prevalence of prediabetes and total cholesterol in borderline levels and risks in the 2016-population. We found correlation in men and women regarding glucose-triglycerides, glucose-cholesterol, and cholesterol-triglycerides in both populations. Conclusions: in the sample of 2016 there was increase in young adults at risk of developing type 2 diabetes mellitus and atherosclerosis by what is needed to develop strategies to improve lifestyle..(AU)

Objetivo: a nivel global se ha observado un desplazamiento hacia la derecha los promedios de glucosa y colesterol en sangre. Esto aumenta la probabilidad de desarrollar enfermedades no transmisibles. Por ello el objetivo fue analizar la prevalencia de anomalías en adultos jóvenes. Materiales y métodos: es un estudio observacional,analítico, transversal, no probabilistico. Se realizó en el Centro Clínico de una Escuela de Medicina en el sureste de México. Participaron poblaciones de nuevo ingreso a una facultad de medicina, 367 jóvenes en 2011, y 430 en 2016. Mediciones principales.Glucemia, trigliceridemia y colesterolemia en ayuno. Se analizaron estadísticos de tendencia central, dispersiones y correlaciones para los grupos. También Chi2 para categorías clínicas. Resultados: se encontraron incrementos significativos en mujeres de glucemia entre 2011 y 2016, t = -4.582 (p = 0.0001) y colesterolemia, t = -9.124 (p= 0.0001). Los hombres también tuvieron incrementos significativos en glucemia con t= -6.428 (p = 0.0001) y colesterolemia con t = -9.499 (p = 0.0001). Hubo mayor revalencia de prediabetes y colesterol total en niveles mayores al deseable en la población de 2016. Se encontró correlación en mujeres y hombres entre glucosa-triglicéridos, glucosa-colesterol y colesterol triglicéridos en ambas poblaciones. Conclusiones: en 2016 hubo incremento en la proporción de individuos en riesgo de desarrollar diabetes de tipo 2 y aterosclerosis..(AU)

Association between insulin resistance and the development of cardiovascular disease.

For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

Efficacy and safety of aripiprazole for the treatment of schizophrenia: an overview of systematic reviews.

PURPOSE: To conduct an overview to summarize the efficacy and safety of aripiprazole for the treatment of schizophrenia. METHODS: A literature search was performed in PubMed, the Cochrane Library, LILACS, and the Centre for Reviews and Dissemination, for articles published until March 31, 2017. We included systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy, and/or the safety of aripiprazole, for patients with schizophrenia. Two authors independently performed the study selection, data extraction, and quality assessment. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the Risk of Bias in Systematic Review (ROBIS) tool were used to appraise the quality of evidence and the risk of bias in the reviews, respectively. RESULTS: Fourteen studies fulfilled the inclusion criteria. Aripiprazole showed efficacy similar to that of both typical and atypical antipsychotic drugs (except olanzapine and amisulpride). Aripiprazole caused significantly lower weight gain and alterations in glucose and cholesterol levels, as compared to clozapine, risperidone, and olanzapine. In addition, aripiprazole caused significantly fewer general extrapyramidal side effects, less use of antiparkinsonian drugs, and akathisia, compared with typical antipsychotic drugs and risperidone. The overall quality of evidence in the reviews ranged from "very low" to "moderate," principally because of the risk of bias of original trials, inconsistency, and imprecision in the outcomes. According to the ROBIS tool, there are four reviews with "high" risk of bias and five with "unclear" risk of bias. CONCLUSIONS: Aripiprazole exhibited efficacy similar to that of other antipsychotic drugs and a better safety profile than that of typical (i.e., less some extrapyramidal side effects) and atypical (i.e., less metabolic changes) antipsychotic drugs.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders.

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

The association between insulin resistance, metabolic variables, and depressive symptoms in Mexican-American elderly: A population-based study.

OBJECTIVE: Depressive symptoms are common among older adults with obesity and diabetes. Nonetheless, the mechanisms for this association are not clear but may involve changes in the insulin cascade signaling. We aimed to investigate the association, and potential mediators, between obesity, insulin resistance, and depressive symptoms among older adults from a homogenous cohort of Mexican-Americans. METHODS: We included a total of 500 Mexican-American older adults assessed in the Cameron County Health Study. We evaluated depressive symptoms using the Center for Epidemiologic Survey Depression Scale (CES-D). Central obesity was defined by waist circumference. Insulin resistance was evaluated by the HOMA-IR index. We estimated the association between obesity, insulin resistance, and depressive symptoms by carrying out univariate and multivariate regression analyses. RESULTS: In unadjusted regression analysis, HOMA-IR (unstandardized ß = 0.31 ± 0.12, P = 0.007), waist circumference (unstandardized ß = 0.066 ± 0.0.028, P = 0.017), and Hb1Ac levels (unstandardized ß = 0.52 ± 0.24, P = 0.03) were significantly associated with CES-D scores. The association of HOMA-IR and CES-D remained statistically significant after controlling for socio-demographic and clinical variables in multivariate analysis (unstandardized ß = 0.28 ± 0.11, P = 0.01). CONCLUSION: Our results suggest that depressive symptoms are associated with insulin resistance in older Mexican-American adults. In addition, poorer glucose control and obesity are important mediators of this relationship. Additional studies are needed to evaluate whether interventions that increase insulin sensitivity can also reduce depressive symptoms in this population.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

The Metabolic Syndrome and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. METHODS AND RESULTS: We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987-2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow-up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P<0.001). After adjustment for participant demographics and clinical factors other than components of the metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37-2.12, P<0.001). This relationship was not modified by sex (interaction P=0.10) or race (interaction P=0.62) and was mediated by the metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19-1.44, P<0.001). Of the 5 components, elevated blood pressure, impaired fasting glucose, and low high-density lipoprotein were independently associated with sudden cardiac death. CONCLUSIONS: We observed that the metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components.

Evaluación de tres metodologías para la predicción del riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad / Evaluation of three methodologies for risk prediction of impaired glucose metabolism in overweighed and obese subjects

Introducción: en la actualidad, en Cuba no existe una estrategia establecida para la pesquisa de las alteraciones del metabolismo de la glucosa. Objetivo: evaluar la capacidad diagnóstica de tres metodologías para predecir el riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad. Métodos: se realizó un estudio de evaluación diagnóstica longitudinal, con los datos de 90 sujetos con edades comprendidas entre 25 y 70 años, analizados 2,5 años después de la evaluación inicial. Se obtuvo la edad, el sexo, los antecedentes patológicos personales, los medicamentos empleados, el peso, la talla, el perímetro de cintura y la tensión arterial, así como las concentraciones de glucosa al inicio y a los 2,5 años ulteriores, la insulina y los triglicéridos, además de calcular la resistencia a la insulina en la evaluación inicial. Se utilizó un modelo de puntaje-riesgo para la diabetes tipo 2. Resultados: la frecuencia de alteraciones del metabolismo de la glucosa (glucemia alterada en ayuna y diabetes tipo 2) a los 2,5 años ulteriores, de acuerdo con la presencia previa o no en los sujetos de glucemia alterada en ayunas, resistencia a la insulina y riesgo moderado/alto de diabetes tipo 2, fue superior en los sujetos con glucemia alterada en ayuna previa (72,4 por ciento [21/29]), con resistencia a la insulina al inicio (65,6 por ciento [40/61]) y con riesgo moderado/alto (54,4 por ciento [43/79]), en relación con aquellos sin glucemia alterada en ayuna, sin resistencia a la insulina y con riesgo bajo de diabetes (41,0 por ciento [25/61], p= 0,005; 20,7 por ciento [6/29], p= 0,006 y 27,3 por ciento [3/11], p< 0,0001 respectivamente). La resistencia a la insulina y el riesgo de diabetes tipo 2 moderado/alto mostraron una elevada sensibilidad para identificar sujetos con alteraciones del metabolismo de la glucosa (87,0 y 93,5 por ciento respectivamente), por el contrario de la glucemia alterada en ayunas, que mostró una baja sensibilidad (45,7 por ciento). De los 19 sujetos que desarrollaron diabetes tipo 2 a los 2,5 años, el 100 por ciento presentó riesgo de diabetes tipo 2 moderado/alto y 94,7 por ciento resistencia a la insulina al inicio. Conclusiones: la resistencia a la insulina y el riesgo de diabetes tipo 2 podrían ser de gran utilidad en la identificación de individuos con alto riesgo para padecer diabetes(AU)

Introduction: at present, there is no set strategy in Cuba for the screening of impaired glucose metabolism. Objective: to evaluate the diagnostic capacity of three methodologies to predict the risk of impaired glucose metabolism in overweighed and obese individuals. Methods: a longitudinal diagnostic evaluation study was carried out using data from 90 subjects aged 25 to 70 years, which were analyzed two and a half years after the initial assessment. Information about age, sex, personal pathological history, used medication, weight, height, waist circumference and blood pressure as well the glucose concentrations at the beginning and two and a half years later, insulin and triglyceride indexes was collected in addition to estimating the insulin-resistance index in the initial evaluation. A risk-score model for type 2 diabetes was also used. Results: the frequency of impaired glucose metabolism (impaired fasting glycemia and type 2 diabetes) after two and a half years, according to the previous existence or not of impaired fasting glycemia, insulin resistance and moderate/high risk of type 2 diabetes, was higher in subjects with previous impaired fasting glycemia (72,4 percent [21/29]), with insulin resistance at the beginning (65.6 percent [40/61]) and with moderate/high risk (54,4 percent [43/79]) than in those individuals without impaired fasting glycemia, insulin resistance and with low diabetes risk (41.0 percent [25/61], p= 0,005; 20.7 percent [6/29], p= 0.006 and 27.3 percent [3/11], p< 0.0001, respectively). Insulin resistance index and moderate/high risk of type 2 diabetes showed high sensitivity to identify subjects with impaired glucose metabolism (87.0 and 93.5 percent, respectively), in contrast to impaired fasting glucose whose sensitivity was low (45.7 percent). Of 19 individuals who developed type 2 diabetes two and a half years later, 100 percent had moderate/high risk of type 2 diabetes and 94.7 percent had insulin resistance at the beginning. Conclusions: insulin resistance and risk of type 2 diabetes could be very useful in detecting individuals with high risk of developing diabetes(AU)

Evaluación de tres metodologías para la predicción del riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad / Evaluation of three methodologies for risk prediction of impaired glucose metabolism in overweighed and obese subjects

Introducción: en la actualidad, en Cuba no existe una estrategia establecida para la pesquisa de las alteraciones del metabolismo de la glucosa. Objetivo: evaluar la capacidad diagnóstica de tres metodologías para predecir el riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad. Métodos: se realizó un estudio de evaluación diagnóstica longitudinal, con los datos de 90 sujetos con edades comprendidas entre 25 y 70 años, analizados 2,5 años después de la evaluación inicial. Se obtuvo la edad, el sexo, los antecedentes patológicos personales, los medicamentos empleados, el peso, la talla, el perímetro de cintura y la tensión arterial, así como las concentraciones de glucosa al inicio y a los 2,5 años ulteriores, la insulina y los triglicéridos, además de calcular la resistencia a la insulina en la evaluación inicial. Se utilizó un modelo de puntaje-riesgo para la diabetes tipo 2. Resultados: la frecuencia de alteraciones del metabolismo de la glucosa (glucemia alterada en ayuna y diabetes tipo 2) a los 2,5 años ulteriores, de acuerdo con la presencia previa o no en los sujetos de glucemia alterada en ayunas, resistencia a la insulina y riesgo moderado/alto de diabetes tipo 2, fue superior en los sujetos con glucemia alterada en ayuna previa (72,4 por ciento [21/29]), con resistencia a la insulina al inicio (65,6 por ciento [40/61]) y con riesgo moderado/alto (54,4 por ciento [43/79]), en relación con aquellos sin glucemia alterada en ayuna, sin resistencia a la insulina y con riesgo bajo de diabetes (41,0 por ciento [25/61], p= 0,005; 20,7 por ciento [6/29], p= 0,006 y 27,3 por ciento [3/11], p< 0,0001 respectivamente). La resistencia a la insulina y el riesgo de diabetes tipo 2 moderado/alto mostraron una elevada sensibilidad para identificar sujetos con alteraciones del metabolismo de la glucosa (87,0 y 93,5 por ciento respectivamente), por el contrario de la glucemia alterada en ayunas, que mostró una baja sensibilidad (45,7 por ciento). De los 19 sujetos que desarrollaron diabetes tipo 2 a los 2,5 años, el 100 por ciento presentó riesgo de diabetes tipo 2 moderado/alto y 94,7 por ciento resistencia a la insulina al inicio. Conclusiones: la resistencia a la insulina y el riesgo de diabetes tipo 2 podrían ser de gran utilidad en la identificación de individuos con alto riesgo para padecer diabetes(AU)

Introduction: at present, there is no set strategy in Cuba for the screening of impaired glucose metabolism. Objective: to evaluate the diagnostic capacity of three methodologies to predict the risk of impaired glucose metabolism in overweighed and obese individuals. Methods: a longitudinal diagnostic evaluation study was carried out using data from 90 subjects aged 25 to 70 years, which were analyzed two and a half years after the initial assessment. Information about age, sex, personal pathological history, used medication, weight, height, waist circumference and blood pressure as well the glucose concentrations at the beginning and two and a half years later, insulin and triglyceride indexes was collected in addition to estimating the insulin-resistance index in the initial evaluation. A risk-score model for type 2 diabetes was also used. Results: the frequency of impaired glucose metabolism (impaired fasting glycemia and type 2 diabetes) after two and a half years, according to the previous existence or not of impaired fasting glycemia, insulin resistance and moderate/high risk of type 2 diabetes, was higher in subjects with previous impaired fasting glycemia (72,4 percent [21/29]), with insulin resistance at the beginning (65.6 percent [40/61]) and with moderate/high risk (54,4 percent [43/79]) than in those individuals without impaired fasting glycemia, insulin resistance and with low diabetes risk (41.0 percent [25/61], p= 0,005; 20.7 percent [6/29], p= 0.006 and 27.3 percent [3/11], p< 0.0001, respectively). Insulin resistance index and moderate/high risk of type 2 diabetes showed high sensitivity to identify subjects with impaired glucose metabolism (87.0 and 93.5 percent, respectively), in contrast to impaired fasting glucose whose sensitivity was low (45.7 percent). Of 19 individuals who developed type 2 diabetes two and a half years later, 100 percent had moderate/high risk of type 2 diabetes and 94.7 percent had insulin resistance at the beginning. Conclusions: insulin resistance and risk of type 2 diabetes could be very useful in detecting individuals with high risk of developing diabetes(AU)