Integrative network analysis of differentially methylated regions to study the impact of gestational weight gain on maternal metabolism and fetal-neonatal growth.

Integrative network analysis (INA) is important for identifying gene modules or epigenetically regulated molecular pathways in diseases. This study evaluated the effect of excessive gestational weight gain (EGWG) on INA of differentially methylated regions, maternal metabolism and offspring growth. Brazilian women from "The Araraquara Cohort Study" with adequate pre-pregnancy body mass index were divided into EGWG (n=30) versus adequate gestational weight gain (AGWG, n=45) groups. The methylome analysis was performed on maternal blood using the Illumina MethylationEPIC BeadChip. Fetal-neonatal growth was assessed by ultrasound and anthropometry, respectively. Maternal lipid and glycemic profiles were investigated. Maternal triglycerides-TG (p=0.030) and total cholesterol (p=0.014); fetus occipito-frontal diameter (p=0.005); neonate head circumference-HC (p=0.016) and thoracic perimeter (p=0.020) were greater in the EGWG compared to the AGWG group. Multiple linear regression analysis showed that maternal DNA methylation was associated with maternal TG and fasting insulin, fetal abdominal circumference, and fetal and neonate HC. The DMRs studied were enriched in 142 biological processes, 21 molecular functions,and 17 cellular components with terms directed for the fatty acids metabolism. Three DMGMs were identified:COL3A1, ITGA4 and KLRK1. INA targeted chronic diseases and maternal metabolism contributing to an epigenetic understanding of the involvement of GWG in maternal metabolism and fetal-neonatal growth.

The relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression on offspring growth and body composition.

Background and objective: Imprinted genes are important for the offspring development. To assess the relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression and offspring growth and body composition. Methods: Thirty-nine overweight/obese and 25 normal weight pregnant women were selected from the "Araraquara Cohort Study" according to their pre-pregnancy BMI. Fetal growth and body composition and newborn growth were assessed, respectively, by ultrasound and anthropometry. The methylation of H19DMR in maternal blood, cord blood, maternal decidua and placental villi tissues was evaluated by methylation-sensitive restriction endonuclease qPCR, and H19 and IGF2 expression by relative real-time PCR quantification. Multiple linear regression models explored the associations of DNA methylation and gene expression with maternal, fetal, and newborn parameters. Results: H19DMR was less methylated in maternal blood of the overweight/obese group. There were associations of H19DMR methylation in cord blood with centiles of fetal biparietal diameter (BPD) and abdominal subcutaneous fat thickness and newborn head circumference (HC); H19DMR methylation in maternal decidua with fetal occipitofrontal diameter (OFD), HC, and length; H19DMR methylation in placental villi with fetal OFD, HC and abdominal subcutaneous fat thickness and with newborn HC. H19 expression in maternal decidua was associated with fetal BPD and femur length centiles and in placental villi with fetal OFD and subcutaneous arm fat. IGF2 expression in maternal decidua was associated with fetal BPD and in placental villi with fetal OFD. Conclusion: To our knowledge, this is the first study to demonstrate associations of imprinted genes variations at the maternal-fetal interface of the placenta and in cord blood with fetal body composition, supporting the involvement of epigenetic mechanisms in offspring growth and body composition.

Excessive Gestational Weight Gain Alters DNA Methylation and Influences Foetal and Neonatal Body Composition.

BACKGROUND: Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition. METHODS: Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated into two groups: adequate gestational weight gain (AGWG, n = 45) and excessive gestational weight gain (EGWG, n = 30). Foetal and neonatal body composition was evaluated via ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition. RESULTS: Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methylated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (EMILIN1, HOXA5, CPT1B, CLDN9, ZFP57, BRCA1, POU5F1, ANKRD33, HLA-B, RANBP17, ZMYND11, DIP2C, TMEM232), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass. CONCLUSION: The methylation pattern in the EGWG group indicated a risk for developing chronic diseases and involvement of maternal DNAm in foetal lean and fat mass and in neonatal fat mass.

Consumption of ultra-processed products is associated with vitamin D deficiency in Brazilian adults and elderly.

Although studies show that the intake of ultra-processed products (UPP) has a negative impact on health, diet quality and dietary vitamin D, its influence on serum concentrations of this vitamin remains unknown; therefore, it is essential to verify the association between the UPP consumption and vitamin D deficiency. This is a cross-sectional, household, population-based study, carried out with 229 individuals aged 20 years or older, residents of the city of Teresina, Piauí, Brazil. Socio-demographic, lifestyle, food consumption and anthropometric data were collected. Food consumption was obtained using a 24-h food recall, and foods were grouped according to the NOVA classification. Plasma concentrations of calcidiol-25 (OH) D3 were determined by HPLC. Crude and adjusted binary logistic regression was applied to estimate the association between UPP consumption and vitamin D deficiency. Most individuals aged 20-39 years were vitamin D deficient (52·1 %). UPP contributed 19·9 % to the energetic intake of the participant's diet. This contribution was higher for individuals with vitamin D deficiency (22·5 %, P = 0·04). In addition, a high intake of UPP was associated with twice the risk of vitamin D deficiency in comparison with low consumption of UPP (OR: 2·05; CI 1·06, 4·50; P: 0·04). Our results suggest that the consumption of UPP may have a negative impact on serum concentrations of vitamin D; more studies are needed.

Maternal plasma transforming growth factor-β1 (TGF-β1) and newborn size: the Araraquara Cohort Study

Abstract Objective To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. Methods This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. Results Maternal plasma TGF-β1 concentration was inversely associated with newborn weight (β= -43.0; p= 0.012), length (β= -0.16, p= 0.028), head circumference (β= -0.13, p= 0.004), ponderal index (β= -0.32, p= 0.011) and fat-free mass (β= -0.05, p= 0.005). However, the association persisted just for head circumference (β= -0.26; p= 0.030) and ponderal index (β= - 0.28; p= 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. Conclusions Maternal plasma TGF-β1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-β1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Maternal plasma transforming growth factor-ß1 (TGF-ß1) and newborn size: the Araraquara Cohort Study.

OBJECTIVE: To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. METHODS: This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. RESULTS: Maternal plasma TGF-ß1 concentration was inversely associated with newborn weight (ß = -43.0; p = 0.012), length (ß = -0.16, p = 0.028), head circumference (ß = -0.13, p = 0.004), ponderal index (ß = -0.32, p = 0.011) and fat-free mass (ß = -0.05, p = 0.005). However, the association persisted just for head circumference (ß = -0.26; p = 0.030) and ponderal index (ß = - 0.28; p = 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. CONCLUSIONS: Maternal plasma TGF-ß1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-ß1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Nutritional Global Status and Its Impact in Crohn's Disease.

BACKGROUND: Malnutrition among inflammatory bowel disease (IBD) subjects is well documented in literature and may emerge from factors including inadequate dietary intake, malabsorption and disease activity. The aim of this study was to complete a comprehensive nutrition assessment and explore what possibilities may help bring a better quality of life for IBD subjects. METHODS: Nutritional status based on biochemical tests, body composition and body mass index (BMI). Food intake was assessed by an alternate 3-day food record and the adequacy of intake was evaluated according to national and international references. Clinical disease activity was evaluated by the Harvey-Bradshaw index and CRP levels. RESULTS: The study included 217 patients and 65 controls, where 54.4% of these patients were classified as normal weight with a mean BMI lower than controls (23.8 ± 4.9 versus 26.9 ± 4.8 kg/m2, P = 0.02). Patients with disease activity showed more overweight and obesity than patients with controlled disease. Vitamin B12 deficiency was present in 19% of Crohn's disease (CD), mainly in patients with ileal commitment and small bowel resections. Anemia was present in 21.7% of patients, being more common in patients with active disease (25%) and bowel resection (23%). Regarding calorie intake (EI), CD group ingested more than controls (1986.3 ± 595.9 kcal versus 1701.8 ± 478.9 kcal; P = 0.003). CONCLUSIONS: CD patients presented micronutrient deficiency when compared with controls, explained for other reasons than intake restrictions. Also, fat excess might have contributed to disease burden as continuously reported in the literature.

Nutritional status and vitamin A and zinc levels in patients with kala-azar in Piauí, Brazil.

INTRODUCTION: Malnutrition and kala-azar (or visceral leishmaniasis) are significant public health problems in different parts of the world. Immunity and susceptibility to infectious and parasitic diseases are directly linked to the host's nutritional state, but little is known about the interaction between nutrition and kala-azar. This study aimed to evaluate nutritional status with kala-azar and correlate these findings with the clinical and laboratory manifestations of the disease, and zinc and retinol levels. METHODS: This was a cross-sectional study of 139 patients with kala-azar. Nutritional status classification was performed according to international recommendations. Parametric or nonparametric tests were applied whenever indicated in a two-sided test with a 5% significance level. RESULTS: Weight loss and malnutrition were more frequent in adults. Body mass index-for-age, fat area of the arm, and upper arm muscle area were significantly associated with probability of death. The presence of human immunodeficiency virus, hepatomegaly, and splenomegaly was correlated with nutritional assessment. Blood leukocyte and lymphocyte, serum creatine, and vitamin A levels were significantly higher in adult men. Vitamin A levels were highly associated with the level of hemoglobin and C-reactive protein (CRP) in multivariate analysis. All patients had reduced plasma zinc levels, but this finding had no association with the outcome variables. CONCLUSIONS: Malnutrition was correlated with severe disease and was more prevalent in older people with kala-azar. Vitamin A deficiency was associated with hemoglobin and CRP. Zinc levels were reduced in patients with kala-azar.

Nutritional status and vitamin A and zinc levels in patients with kala-azar in Piauí, Brazil

Abstract INTRODUCTION: Malnutrition and kala-azar (or visceral leishmaniasis) are significant public health problems in different parts of the world. Immunity and susceptibility to infectious and parasitic diseases are directly linked to the host's nutritional state, but little is known about the interaction between nutrition and kala-azar. This study aimed to evaluate nutritional status with kala-azar and correlate these findings with the clinical and laboratory manifestations of the disease, and zinc and retinol levels. METHODS: This was a cross-sectional study of 139 patients with kala-azar. Nutritional status classification was performed according to international recommendations. Parametric or nonparametric tests were applied whenever indicated in a two-sided test with a 5% significance level. RESULTS: Weight loss and malnutrition were more frequent in adults. Body mass index-for-age, fat area of the arm, and upper arm muscle area were significantly associated with probability of death. The presence of human immunodeficiency virus, hepatomegaly, and splenomegaly was correlated with nutritional assessment. Blood leukocyte and lymphocyte, serum creatine, and vitamin A levels were significantly higher in adult men. Vitamin A levels were highly associated with the level of hemoglobin and C-reactive protein (CRP) in multivariate analysis. All patients had reduced plasma zinc levels, but this finding had no association with the outcome variables. CONCLUSIONS: Malnutrition was correlated with severe disease and was more prevalent in older people with kala-azar. Vitamin A deficiency was associated with hemoglobin and CRP. Zinc levels were reduced in patients with kala-azar.

The Validity of Children's Fruit and Vegetable Intake Using Plasma Vitamins A, C, and E: The SAYCARE Study.

Despite that fruits and vegetables are key elements for health promotion, there are limited studies validating their intake in children. We aimed to validate the SAYCARE (South American Youth/Child Cardiovascular and Environmental) Study Food Frequency Questionnaire (FFQ) and the combination of the FFQ frequency of intake with the 24 h-dietary-recall (24 h-DR) (mean of 3 days), for children's fruit and vegetable intake. The reference methods were plasma dosages of ß-carotene, retinol, ascorbic acid, and α-tocopherol, which were collected in the school environment. It is a validity study in a subsample of 45 children aged 6-10 years participating in the SAYCARE Study, from São Paulo (Brazil). The FFQ was answered by the parents/guardians over the previous 3 months; the 24 h-DR was answered three times (two weekdays by nutritionists, one weekend day by parents/guardians). The mean fruit and vegetable intake (combined with frequency of intake) was calculated using the multiple source method (MSM). Multiple linear regression showed pooled correlation coefficients of 0.29 to 0.35 for the reported fruit and vegetable intake estimated by the FFQ and the MSM, respectively. The SAYCARE FFQ is an accurate and useful tool for ranking fruit and vegetable intake in children between 6-10 years from the SAYCARE Study.

Cord blood concentrations of leptin, zinc-α2-glycoprotein, and adiponectin, and adiposity gain during the first 3 mo of life.

OBJECTIVES: Adipose tissue development starts in intrauterine life and cytokines are involved in this process. Therefore, understanding the role of cytokines in the fat mass gain of infants is crucial to prevent obesity later in life. Furthermore, recent evidence indicates a sex-specific link between cytokines and adipose tissue development. The objective of this study was to assess sex-specific relationships of cord blood concentrations of the cytokines leptin, zinc-α2-glycoprotein (ZAG), and adiponectin with infant adiposity during the first 3 mo of life. METHODS: This was a prospective cohort study of 104 mother-infant pairs that were selected from a maternity hospital in Sao Paulo, Brazil. Cord blood leptin, ZAG, and adiponectin were determined by enzyme-linked immunosorbent assays. The body composition of the infants was assessed monthly by air displacement plethysmography. A multiple linear regression analysis was conducted with the average fat mass gain from birth to the third month of life as the outcome and cord blood leptin, ZAG, and adiponectin as the variables of interest. RESULTS: Leptin was inversely associated with fat mass gain in the first 3 mo of life (P = 0.003; adjusted R2 = 0.09). There were inverse associations of leptin (P = 0.021), ZAG (P = 0.042), and maternal body mass index (P = 0.04) with fat mass gain in girls (adjusted R2 = 0.29) but fat mass gain in boys was positively associated with gestational age (P = 0.01; adjusted R2 = 0.15). CONCLUSIONS: The results of this study suggest that adiposity programming is sex-specific, which highlights the need to investigate the different metabolic mechanisms that are involved in adipogenesis.

The relationship between serum retinol concentrations and subclinical infection in rural Brazilian children / Relação entre as concentrações séricas de retinol e a infecção subclínica em crianças rurais brasileiras

ABSTRACT Objective To evaluate the relationship between serum retinol concentrations and subclinical infection in children from rural settlements. Methods A cross-sectional population-based study was carried out in nine rural settlements in the northeastern region of Brazil, involving 118 children aged 6 to 59 months. The relationship between serum retinol and C-Reactive Protein levels, an important marker of infectious and inflammatory processes, was investigated by multiple linear regression, controlling for demographic, socioeconomic and nutritional variables. Serum retinol and C-Reactive Protein were measured, respectively, by High Performance Liquid Chromatography and immunoturbidimetric assay in automated equipment. Results Vitamin A deficiency (retinol <0.70μmol/L) was identified in 9.3% of the children. C-Reactive Protein was the only predictor of retinol concentrations in the final regression model, causing a 0.728μmol/L reduction in retinol concentrations in the studied children (p=0.008). Conclusion Vitamin A deficiency is a problem of mild/moderate severity and measures to control infectious diseases in this population are fundamental to prevent and/or combat this problem.

RESUMO Objetivo Esta pesquisa teve por objetivo avaliar a relação entre concentrações séricas de retinol e infecção subclínica, em crianças de assentamentos rurais. Métodos Trata-se de estudo transversal, de base populacional, realizado em nove assentamentos rurais na região nordeste do Brasil, envolvendo 118 crianças de 6 a 59 meses de idade. A relação entre retinol sérico e níveis de proteína C-reativa, importante marcador de processos infecciosos e inflamatórios, foi investigada por análise de regressão linear múltipla, controlando-se variáveis demográficas, socioeconômicas e nutricionais. O retinol sérico e a proteína C-reativa foram medidos, respectivamente, por Cromatografia Líquida de Alta Performance e ensaio imunoturbidimétrico em equipamento automatizado. Resultados A deficiência de vitamina A (retinol <0,70μmll/L) foi identificada em 9,3% das crianças. A proteína C-reativa foi o único preditor de concentrações de retinol no modelo de regressão final, causando uma redução de 0,728μmol/L nas concentrações de retinol nas crianças estudadas (p=0,008). Conclusão A pesquisa concluiu que a deficiência de vitamina A é um problema de severidade leve/moderada, sendo fundamental a adoção de medidas para controlar doenças infecciosas nessa população, bem como para prevenir e/ou combater o problema.

The impact of dark chocolate intake on arterial elasticity in individuals with HIV/AIDS undergoing ART: a randomized, double-blind, crossover trial.

An increase in the frequency of cardiovascular diseases has been observed in the HIV/AIDS population. Studies involving healthy subjects or subjects with other diseases have shown benefits of chocolate supplementation on endothelial function and vasodilation. We evaluate the impact of chocolate consumption on arterial elasticity in people living with human immunodeficiency virus - PLHIV. A double-blind, crossover trial including 110 PLHIV (19 to 59 years) on antiretroviral therapy - ART for at least 6 months and with a viral load of <500 copies per mL was conducted. All subjects were randomly assigned to 15-d dietary supplements containing dark chocolate or placebo with a 15-d washout period. Each participant received one of the two sequences: A (dark chocolate, placebo chocolate); B (placebo chocolate, dark chocolate). Arterial elasticity was measured using the HDI/PulseWave™ CR-2000 CardioVascular Profiling System®. Body composition, lipid profile, C-reactive protein, and thiobarbituric acid reactive substances were also assessed. Analysis of variance (ANOVA) for repeated measures using the Stata 11.0® program was used for cross-over analysis. Most subjects were men (59.0%) and Caucasian (46.1%) and the mean age was 44.6 ± 7.1 years. The mean time since diagnosis of HIV infection was 13.7 ± 5.3 years and the mean duration of ART was 12.9 ± 4.2 years. Chocolate consumption resulted in significant alterations in the large artery elasticity index - LAEI (p = 0.049) and the mean concentration of HDL-c was higher after supplementation with dark chocolate (p = 0.045). This is the first study to evaluate the effect of chocolate on arterial elasticity in PLHIV. The results showed that dark chocolate consumption for 15 days improved the elastic properties of the LAEI in PLHIV. These findings, added to the noninvasive method used, may expand the knowledge of CVDs in this population.

Fish oil and vitamin E change lipid profiles and anti-LDL-antibodies in two different ethnic groups of women transitioning through menopause / El aceite de pescado y la vitamina E modifican el perfil lipídico y los anticuerpos anti-ldl en dos grupos étnicos diferentes de mujeres en transición hacia la menopausia

Background: studies have investigated the relationship between the transition through menopause and cardiovascular diseases. White population, generally, have lower levels of traditional coronary heart risk factors, particularly dyslipidemia, hypertension, obesity, and diabetes, and lower rates of coronary heart disease mortality, than black population. Furthermore many studies have shown the cardioprotective and anti-inflammatory effects of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) of marine origin. The aim of this study was to investigate the effect of omega-3 supplementation, combined or not with vitamin E, on oxidative biomarkers and lipid profiles in nonwhite and white women with dyslipidemia transitioning through menopause. Methods: a randomized, double-blind, placebo-controlled trial was conducted. Seventy-four eligible women were assigned to receive: fish oil, fish oil plus vitamin E and placebo for three months. At baseline, 45 and 90 days blood sample for biochemical variables and biomarkers of oxidative stress were taken. Socioeconomic and lifestyle variables were collected with standardized questionnaires. Results: after 90 days the fish oil plus vitamin E treated group had a significant decrease in total cholesterol and LDL-C. Furthermore, there was a decrease in anti-LDL- autoantibodies after 45 days. Plasma TBARS concentrations were increased after 90 days in the group receiving only fish oil when compared to the placebo and fish oil-vitamin E groups. All of the effects observed were independent of ethnic group. Conclusion: supplementation with fish oil and vitamin E reduced total cholesterol and LDL-C, but had opposite. effects on oxidative stress compared to supplementation with fish oil alone (AU)

Introducción: diversos estudios han investigado la relación entre la transición a la menopausia y las enfermedades cardiovasculares. Generalmente, la población de etnia blanca posee bajos niveles de factores de riesgo coronarios, particularmente dislipidemia, hipertensión, obesidad, diabetes y bajas tasas de mortalidad por enfermedades del corazón en comparación con la población de etnia negra. Además, varios estudios demostraron efectos cardioprotectores y antiinflamatorios provenientes de ácidos grasos poliinsaturados omega-3 (ácido eicosapentaenoico y ácido docosahexaenoico) de origen marino. El objetivo del estudio fue investigar el efecto de la suplementación de omega-3 combinado o no con vitamina E en biomarcadores oxidativos y perfiles lipídicos en mujeres blancas y no blancas con dislipidemia en transición hacia la menopausia. Métodos: fue realizado un estudio randomizado, duplo-ciego, placebo-controlado. Setenta y cuatro mujeres elegibles fueron escogidas para recibir: aceite de pescado, aceite de pescado con vitamina E y placebo durante tres meses. Fueron recogidas muestras de sangre en de referencia, 45 y 90 días para realizar exámenes bioquímicos y de biomarcadores para estrés oxidativo. Las variables socioeconómicas y de estilo de vida fueron recogidas por medio de cuestionarios estandarizados. Resultados: después de 90 días, el grupo tratado con aceite de pescado con vitamina E tuvo una disminución significativa para colesterol total y LDL-C. Además, hubo una disminución de anticuerpos anti-LDL después de 45 días. La concentración de plasma TBARS aumentó después de 90 días en el grupo que recibió solamente aceite de pescado, comparado con los grupos placebo y aceite de pescado con vitamina E. Todos los efectos observados fueron independientes del grupo étnico. Conclusión: la suplementación con aceite de pescado y vitamina E redujo el colesterol total y LDL-C, pero tuvo un efecto opuesto en el estrés oxidativo comparado con la suplementación solamente con aceite de pescado (AU)

Vitamin E concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 µmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment.

Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review.

This study reviewed the lipid profile of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in relation to use of antiretroviral therapy (ART), and its different classes of drugs. A total of 190 articles published in peer-reviewed journals were retrieved from PubMed and LILACS databases; 88 of them met the selection criteria and were included in the review. Patients with HIV/AIDS without ART presented an increase of triglycerides and decreases of total cholesterol, low density lipoprotein (LDL-c), and high density lipoprotein (HDL-c) levels. Distinct ART regimens appear to promote different alterations in lipid metabolism. Protease inhibitors, particularly indinavir and lopinavir, were commonly associated with hypercholesterolemia, high LDL-c, low HDL-c, and hypertriglyceridemia. The protease inhibitor atazanavir is apparently associated with a more advantageous lipid profile. Some nucleoside reverse-transcriptase inhibitors (didanosine, stavudine, and zidovudine) induced lipoatrophy and hypertriglyceridemia, whereas abacavir increased the risk of cardiovascular diseases even in the absence of apparent lipid disorders, and tenofovir resulted in lower levels of cholesterol and triglycerides. Although non-nucleoside reverse-transcriptase inhibitors predisposed to hypertriglyceridemia and hypercholesterolemia, nevirapine was particularly associated with high HDL-c levels, a protective factor against cardiovascular diseases. Therefore, the infection itself, different classes of drugs, and some drugs from the same class of ART appear to exert distinct alterations in lipid metabolism.

Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review / Perfil lipídico de pacientes infectados pelo HIV em relação à terapia antirretroviral: uma revisão

This study reviewed the lipid profile of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in relation to use of antiretroviral therapy (ART), and its different classes of drugs. A total of 190 articles published in peer-reviewed journals were retrieved from PubMed and LILACS databases; 88 of them met the selection criteria and were included in the review. Patients with HIV/AIDS without ART presented an increase of triglycerides and decreases of total cholesterol, low density lipoprotein (LDL-c), and high density lipoprotein (HDL-c) levels. Distinct ART regimens appear to promote different alterations in lipid metabolism. Protease inhibitors, particularly indinavir and lopinavir, were commonly associated with hypercholesterolemia, high LDL-c, low HDL-c, and hypertriglyceridemia. The protease inhibitor atazanavir is apparently associated with a more advantageous lipid profile. Some nucleoside reverse-transcriptase inhibitors (didanosine, stavudine, and zidovudine) induced lipoatrophy and hypertriglyceridemia, whereas abacavir increased the risk of cardiovascular diseases even in the absence of apparent lipid disorders, and tenofovir resulted in lower levels of cholesterol and triglycerides. Although non-nucleoside reverse-transcriptase inhibitors predisposed to hypertriglyceridemia and hypercholesterolemia, nevirapine was particularly associated with high HDL-c levels, a protective factor against cardiovascular diseases. Therefore, the infection itself, different classes of drugs, and some drugs from the same class of ART appear to exert distinct alterations in lipid metabolism.

Este estudo faz uma revisão sobre o perfil lipídico de pacientes com vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida (HIV/AIDS) em relação ao uso da terapia antirretroviral (TARV), e suas diferentes classes de fármacos. Um total de 190 artigos publicados em revistas indexadas foram selecionados das bases de dados PubMed e LILACS; 88 deles preencheram os critérios de seleção e foram incluídos nesta revisão. Pacientes com HIV/AIDS sem uso de TARV apresentaram aumento de triglicérides e diminuição dos níveis de colesterol total, lipoproteína de baixa densidade (LDL-c) e lipoproteína de alta densidade (HDL-c). Distintos regimes de TARV promoveram diferentes alterações no metabolismo lipídico. Inibidores de protease, particularmente indinavir e lopinavir, foram comumente associados com hipercolesterolemia, aumento de LDL-c, diminuição de HDL-c e hipertrigliceridemia. O inibidor de protease atazanavir aparentemente está associado a menores alterações do perfil lipídico. Alguns inibidores da transcripitase reversa análogos de nucleosídeos (didanosina, estavudina e zidovudina), induziram lipoatrofia e hipertrigliceridemia, enquanto o abacavir aumentou o risco cardiovascular mesmo na ausência de aparentes distúrbios lipídicos, e o tenofovir resultou em menores níveis de colesterol e triglicérides. Embora os inibidores da transcriptase reversa não análogos de nucleosídeos possam predispor a hipertrigliceridemia e hipercolesterolemia, a nevirapina, particularmente, foi associada a maiores níveis de HDL-c, um fator de proteção contra doenças cardiovasculares. Portanto, a própria infecção, diferentes classes de fármacos e alguns fármacos da mesma classe de TARV podem exercer distintas alterações no metabolismo lipídico.

Vitamin A and beta-carotene concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

Micronutrient deficiency is a common condition in HIV-infected individuals and may occur in all stages of the disease. The objective of this cross-sectional study was to compare the concentrations of vitamin A and beta-carotene, micronutrients related to immunity and oxidative stress, in 182 adults with HIV/AIDS, under different highly active antiretroviral therapy (HAART) regimens. Patients were divided into 3 groups according to their HAART regimen: combination of nucleoside analog reverse transcriptase inhibitors (NRTIs) and non-NRTIs; combination of NRTIs, protease inhibitors, and ritonavir; combination of NRTIs and other classes. Multiple linear regression analysis determined the effect of the treatment regimen, time of use, and compliance with the regimen, on vitamin A and beta-carotene concentrations, controlling for the following variables: gender, age, educational level, smoking, physical activity, body mass index, time of infection with HIV, presence of comorbidities, CD4(+) T lymphocyte count, total cholesterol and fractions, and triglyceride levels. There was no significant difference in vitamin A or beta-carotene concentrations in patients under the different HAART regimens. However, approximately 4% of the patients had deficient/low concentrations of vitamin A (<0.70 µmol/L), and 98% showed concentrations of beta-carotene <1.0 µmol/L. In conclusion, HIV/AIDS patients in this region will not benefit from vitamin A supplementation, independently of the HAART regimen utilized, but beta-carotene may be of importance, considering its antioxidant effect.

The effects of lipoic acid and α-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

Antioxidants probably play an important role in the etiology of type 2 diabetes (DM2). This study evaluated the effects of supplementation with lipoic acid (LA) and α-tocopherol on the lipid profile and insulin sensitivity of DM2 patients. A randomized, double-blind, placebo-controlled trial involving 102 DM2 patients divided into four groups to receive daily supplementation for 4 months with: 600 mg LA (n = 26); 800 mg α-tocopherol (n = 25); 800 mg α-tocopherol + 600 mg LA (n = 25); placebo (n = 26). Plasma α-tocopherol, lipid profile, glucose, insulin, and the HOMA index were determined before and after supplementation. Differences within and between groups were compared by ANOVA using Bonferroni correction. Student's t-test was used to compare means of two independent variables. The vitamin E/total cholesterol ratio improved significantly in patients supplemented with vitamin E+LA and vitamin E alone (p ≤ 0.001). There were improvements of the lipid fractions in the groups receiving LA and vitamin E alone or in combination, and on the HOMA index in the LA group, but not significant. The results suggest that LA and vitamin E supplementation alone or in combination did not affect the lipid profile or insulin sensitivity of DM2 patients.

The relationship between arterial elasticity and lipid profile in people with type 1 diabetes mellitus.

A cross-sectional study was carried out to assess small (SAEI) and large (LAEI) arterial elasticity indexes of individuals with T1DM, and its relationship with their lipid profile. There were associations between SAEI and total cholesterol and waist-hip ratio (R(2)=0.29). Most of the individuals investigated showed low measures of SAEI.