Multimodal HIIT is more efficient than moderate continuous training for management of body composition, lipid profile and glucose metabolism in the diabetic elderly / El entrenamiento multimodal es más eficiente que el entrenamiento continuo moderado para el manejo de la composición corporal, el perfil de lípidos y el metabolismo de la glucosa en adultos mayores diabéticos

The exercise could play a central role to the fat management and glucose metabolism what can be a critical role in the health status of diabetic people, but the high intense exercise remains with controversial data about their effects. To identify the effect of the multimodal high-intensity interval training on body composition, lipid profile, and glucose metabolism in elderly diabetics. Methods: Elderly diabetic individuals (n = 48) were randomly divided in a Sedentary Control (SC) group, a Moderate-Intensity Continuous Training (MICT) group, and a High-Intensity Interval Training (HIIT) group. MICT and HITT were conducted over 60 days, 3x per week, with 40 minutes of exercise. Blood was collected prior to intervention, at four, and at eight weeks subsequently to assess glucose metabolism and lipid profiles. Body composition was determined before and after the intervention period. To verify the normality Kolmogorov-Smirnov statistical test was performed, followed by student "t" test or two-way ANOVA with Bonferroni's post hoc test with significance of 5 % the Cohen's f test to indicate the magnitude of the differences. HIIT significantly lowered cholesterol and triglyceride levels, and significantly lowered blood glucose and glycosylated haemoglobin levels (p<0.05). MICT and HIIT significantly increased levels of high-density lipoprotein, decreased total body mass and body mass index. HIIT resulted in significantly smaller waist circumferences, waist-to-hip ratios, and weight-to-height ratios over 60 days of training. HIIT is more effective than MICT for improving lipid and glycaemic profiles, decreasing body fat, and improving fat distribution elderly diabetics.

El ejercicio podría desempeñar un papel central en el manejo de la grasa y el metabolismo de la glucosa, lo que puede ser un papel crítico en el estado de salud de las personas diabéticas, pero el ejercicio intenso intenso sigue teniendo datos controvertidos sobre sus efectos. El objetivo del estudio fue identificar el efecto del entrenamiento multimodal de intervalos de alta intensidad sobre la composición corporal, el perfil lipídico y el metabolismo de la glucosa en diabéticos de edad avanzada. Los individuos diabéticos de edad avanzada (n = 48) se dividieron aleatoriamente en un grupo de control sedentario (SC), un grupo de entrenamiento continuo de intensidad moderada (MICT) y un grupo de entrenamiento de intervalos de alta intensidad (HIIT). MICT y HITT se realizaron durante 60 días, 3 veces por semana, con 40 minutos de ejercicio. Se recogió sangre antes de la intervención, a las cuatro y a las ocho semanas posteriormente para evaluar el metabolismo de la glucosa y los perfiles de lípidos. La composición corporal se determinó antes y después del período de intervención. Para verificar la normalidad se realizó la prueba estadística de Kolmogorov-Smirnov, seguida de la prueba "t" de Student o ANOVA de dos vías con la prueba post hoc de Bonferroni con una significancia del 5 % de la prueba f de Cohen, indicando las diferencias. HIIT redujo significativamente los niveles de colesterol y triglicéridos, además de reducir de manera importante los niveles de glucosa en la sangre y la hemoglobina glicosilada (p <0.05). MICT y HIIT aumentaron significativamente los niveles de lipoproteína de alta densidad, disminuyeron la masa corporal total y el índice de masa corporal. HIIT resultó en circunferencias de cintura significativamente más pequeñas, relaciones cintura-cadera y relaciones peso-altura durante 60 días de entrenamiento. HIIT es más efectivo que MICT para mejorar los perfiles de lípidos y glucémicos, disminuir la grasa corporal y mejorar la distribución de grasa en los diabéticos de edad avanzada.

Relación entre niveles de vitamina D y perfil lipídico en embarazadas de alto riesgo / Relationship between level of vitamin D and lipid profile in high risk pregnant women

En la Argentina, las embarazadas presentan alta prevalencia (80%) de hipovitaminosis D y de sobrepeso u obesidad (27,4%). Ambas condiciones pueden aumentar la morbimortalidad materno-fetal. Bajos niveles de vitamina D se han relacionado con aumento del colesterol total, LDL, triglicéridos (Tg) y descenso de HDL. Objetivo: evaluar los niveles de 25-hidroxivitamina D (25OHD) y su relación con el perfil lipídico en pacientes embarazadas de alto riesgo. Materiales y métodos: estudio de corte transversal entre septiembre de 2016 y abril de 2017. Se excluyeron pacientes que recibieron suplementos de vitamina D, con disfunción tiroidea no compensada, malabsorción, insuficiencia cardíaca, renal o hepática y dislipidemia familiar. Niveles circulantes de 25OHD < 30 ng/ml se consideraron hipovitaminosis. Resultados: se evaluaron 86 embarazadas de 29,3 ± 7,1 años durante la semana 28 ± 6,5. El IMC pregestacional fue 28,3 ± 6,5 kg/m2 y la ganancia de peso 7 ± 4,3 kg. Perfil lipídico: colesterol total 240 ± 54 mg/dl; LDL 156 ± 54 mg/dl; HDL 66 ± 15 mg/dl; Tg 204 ± 80 mg/dl. La media de 25OHD fue de 23,8 ± 9 ng/ml, con una prevalencia de hipovitaminosis D de 77,9 %. Las pacientes con hipovitaminosis D presentaron mayores valores de colesterol total y LDL (p < 0,05), con tendencia no significativa a presentar mayores valores de Tg. Conclusión: en embarazadas de alto riesgo se observó una alta prevalencia de hipovitaminosis D, asociada con mayores concentraciones de colesterol total y LDL. (AU)

In Argentina, pregnant women have a high prevalence (80 %) of hypovitaminosis D and verweight/obesity (27.4%), conditions that can increase maternal-fetal morbidity and mortality. Low levels of 25-hydroxyvitamin D (25OHD) have been linked to an increase in total cholesterol, LDL cholesterol, triglycerides (TG) and a decrease in HDL cholesterol. Objective: to evaluate the levels of vitamin D and its relationship with the lipid profile in high risk pregnant patients. Materials and methods: cross-sectional study between September 2016 and April 2017. Patients who received vitamin D supplements or had non-compensated thyroid dysfunction, malabsorption, heart failure, renal or hepatic failure, or familial dyslipidemia were excluded. Hypovitaminosis D was defined as a circulating level of 25OHD < 30 ng/ml. Results: We assessed 86 women of 29.3 ± 7.1 years during pregnancy week 28 ± 6.5. Pre-gestational BMI was 28.3 ± 6.5 kg/m2. Their weight gain was 7 ± 4.3 kg. Lipid profile: total cholesterol 240 ± 54 mg/dl; LDL cholesterol 156 ± 54 mg/dl; HDL cholesterol 66 ± 15 mg/dL; TG 204 ± 80 mg/dl. The mean 25OHD level was 23.8 ± 9 ng/ml, with a 77.9 % prevalence of hypovitaminosis D. Patients with hypovitaminosis D had higher values of total cholesterol and LDL cholesterol (p<0.05), and a non-significant trend toward higher triglyceridemia. Conclusion: A high prevalence of hypovitaminosis D, associated with high total and LDL cholesterol was found in high risk pregnant women. (AU)

High-Lard and High-Cholesterol Diet, but not High-Lard Diet, Leads to Metabolic Disorders in a Modified Dyslipidemia Model / Dieta Rica em Banha e Colesterol, mas não Dieta Rica em Banha, Leva a Distúrbios Metabólicos em um Modelo Modificado de Dislipidemia

Abstract Background: In view of the increased global prevalence of cardiovascular and hepatic diseases, the diet lipid content and its relationship with the accumulation of fat in hepatocytes have been investigated as key factors in preventing these diseases. Objective: To evaluate the metabolic effects of a high-lard diet supplemented or not with cholesterol on a modified dyslipidemia model. Methods: We divided 24 adult male Wistar rats into three groups: standard diet (STD - 4% lipids), high-lard diet (HLD - 21% lard), and high-lard and high-cholesterol diet (HL/HCD - 20% lard, 1% cholesterol, 0.1% cholic acid). After six weeks of treatment, blood and liver were collected for biochemical (serum lipid profile and liver enzymes) and morphological analyses. Statistical analysis included one-way analysis of variance (ANOVA), followed by Tukey test for mean comparisons, and a 5% probability was considered statistically significant. Results: Animals fed HL/HCD showed increased total cholesterol, triacylglycerol, LDL-c, non-HDL-c, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) serum levels compared to those fed STD. In addition, the HL/HCD animals presented higher relative liver weight, with moderate macrovesicular hepatic steatosis and inflammatory infiltrate. Conclusion: A high-fat diet with lard (20%) and cholesterol (1%) triggered dyslipidemia with severe liver damage in rats in a shorter experimental time than the previously reported models. The high-lard diet without supplementation of cholesterol led to body weight gain, but not to dyslipidemia.

Resumo Fundamento: Tendo em vista o aumento da prevalência global de doenças cardiovasculares e hepáticas, o conteúdo lipídico da dieta e sua relação com o acúmulo de gordura nos hepatócitos têm sido investigados como fatores-chave na prevenção dessas doenças. Objetivo: Avaliar os efeitos metabólicos de uma dieta rica em banha suplementada com colesterol ou não, em um modelo modificado de dislipidemia. Métodos: Foram divididos 24 ratos Wistar machos adultos em três grupos: dieta padrão (DP - 4% de lipídios), dieta rica em banha (DRB - 21% de banha) e dieta rica em banha e colesterol (DRB/RC - 20% de banha, 1% de colesterol e 0,1% de ácido cólico). Após seis semanas de tratamento, o sangue e o fígado foram coletados para análises bioquímicas (perfil lipídico sérico e enzimas hepáticas) e morfológicas. A análise estatística incluiu análise de variância unidirecional (ANOVA), seguida do teste de Tukey para comparações de médias. Uma probabilidade de 5% foi considerada estatisticamente significativa. Resultados: Animais alimentados com DRB/RC apresentaram um aumento nos níveis séricos de colesterol total, triacilglicerol, LDL-c, não-HDL-c, alanina aminotransferase (ALT) e aspartato aminotransferase (AST) em comparação com aqueles alimentados com DP. Além disso, os animais tratados com DRB/RC apresentaram um peso relativo do fígado maior, com esteatose hepática macrovesicular moderada e infiltrado inflamatório. Conclusão: Uma dieta rica em gordura com banha (20%) e colesterol (1%) desencadeou dislipidemia com danos graves ao fígado em ratos em um tempo experimental menor do que os modelos previamente relatados. A dieta rica em banha sem suplementação de colesterol levou ao ganho de peso corporal, mas não à dislipidemia.

Estudo de parâmetros metabólicos em pacientes não diabéticos com doença hepática gordurosa não alcoólica - importância da dislipidemia / A study of metabolic parameters in non diabetic patients with non alcoholic fatty liver disease - importance of dyslipidemia

ABSTRACT BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.

RESUMO CONTEXTO: Os fatores de risco metabólicos da doença hepática gordurosa não alcoólica (DHGNA) em abstêmios não diabéticos, que constituem um grupo distinto, não são bem definidos. OBJETIVO: Identificar os fatores de risco metabólicos da DHGNA em indivíduos não diabéticos e que não consumam álcool. MÉTODOS: Em um estudo transversal, o efeito dos parâmetros metabólicos (IMC, níveis de lipídios individuais, HbA1c, Homa IR e os componentes da síndrome metabólica) de 150 abstêmios não diabéticos consecutivos (90 com tolerância à glicose normal e 60 pré-diabéticos) em sua NFS (parâmetro de gravidade quantificável da DHGNA) foram estudados por análise de regressão linear. Um estudo similar em separado foi feito nos grupos normais da tolerância da glicose e do pré-diabetes. Esses parâmetros foram comparados com os de 75 abstêmios diabéticos pareados com DHGNA. Para analisar ainda mais a diferença entre a tolerância à glicose normal foi realizada a regressão logística binária dos fatores tomando pré-diabetes e diabetes como variável de desfecho, nos grupos diabéticos e pré-diabéticos. RESULTADOS: Todos os parâmetros metabólicos foram significativamente maiores nos diabéticos comparados aos não diabéticos e em pré-diabéticos comparados àqueles com tolerância normal à glicose, exceto HDL. Os índices TG, HDL e IMC previram significativamente o NFS no geral nos grupos de tolerância normal (R2 ajustado 68,7%, P=0,000) e de glicose normal (R2 ajustado 73,2%, P=0,000), enquanto o IMC, TG, LDL e HbA1c predisseram em pré-diabéticos (R2 ajustado 89%, P=0,000). A síndrome metabólica foi associada significativamente com o NFS nos grupos totais e pré-diabéticos. O TG elevado (odds ratio 1,08), o LDL (odds ratio 1,03) e a HbA1c (odds ratio 11,54) foram positivamente associados ao pré-diabetes em comparação com o grupo normal de tolerância à glicose. CONCLUSÃO: Em abstêmios não diabéticos as dislipidemias são os principais contribuintes para o desenvolvimento da DHGNA.

Association of hypertension and dyslipidaemia with increasing obesity in patients with Type 2 Diabetes Mellitus

The study was performed to estimate the association of hypertension and dyslipidaemia with increasing body weight and obesity in Type II diabetics of Lahore, Pakistan. An observational study was conducted by enrolling 2708 obese diabetics from four diabetes care centres of Lahore, Pakistan. Data was collected for a period of 7 months. Associations were estimated using chi-square, binary and multinomial logistic regression. Data suggested that blood pressure, systolic and diastolic, exhibited continual increase with increasing body weight and obesity class in diabetes patients with 41.8% increase in the prevalence of hypertension in obesity class III subjects (OR; 1.91, p=0.02). Likewise, triglycerides and total cholesterol exhibited continual increase in their mean values with increasing obesity, i-e., an overall increase in the prevalence of dyslipidaemia of 27.2% in obesity class 3 subjects (OR; 1.94, p=0.29). Taken together, this data suggested that hypertension is potentially associated with increasing obesity in diabetics, while dyslipidaemia demonstrated plausible association only with obesity class 3.

Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche

OBJECTIVE: Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to cardiovascular disease. The aim of this study was to analyze the presence of these conditions in patients previously treated at the Universidade Federal do Triângulo Mineiro. METHODS: A total of 130 medical records reported premature adrenarche. One hundred and twenty-two patients were invited to participate, of whom 54 accepted; 34 patients were selected, as they had reached their final height. Anthropometric, blood glucose, insulin, and lipid and hormonal profile (LH, FSH, estradiol, 17α-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone) data were obtained, the HOMA-IR index was calculated, and pelvic ultrasonography was performed. To characterize polycystic ovary syndrome and metabolic syndrome, the Rotterdam and International Diabetes Federation criteria, respectively, were used. Data were analyzed according to measures of dispersion, frequency and correlations of interest. RESULTS: The age of the participants ranged from 15.2 to 28.2 years/months; 23.5% of the patients were overweight, 11.8% were obese, 29.4% had a large waist circumference, and 8.8% were hypertensive. None of the patients had altered glucose levels, and insulin levels and HOMA-IR were elevated in 29.4% and 38.2% of the participants, respectively; 14.7% of the patients exhibited acanthosis nigricans. The lipid profiles of the participants were variable, and one patient (2.9%) had metabolic syndrome. Polycystic ovary syndrome was found in 41.2% of patients. CONCLUSION: The percentage of patients with polycystic ovary syndrome who also had overweight, obesity and insulin resistance corroborates the literature data about the need for follow-up aiming at interventions, especially for conditions associated with cardiometabolic risk.

Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2 / Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Dyslipidemia and maternal obesity: Prematurity and neonatal prognosis / Dislipidemia e obesidade materna: prematuridade e prognóstico neonatal

Summary Objective: To identify the changes caused by dyslipidemia and obesity in pregnancy suggesting causes for premature birth, and the prognosis for the newborn. Method: Systematic review based on the Medline, Lilacs, Embase and Cochrane library databases between 1996 and 2016. The search for studies included the following keywords: "dyslipidemia, pregnancy, obesity, preterm birth." A protocol was programmed and a protocol for inclusion/exclusion of studies was implemented. Results: Of the 5,789 articles initially selected between March 1996 and July 2016, only 32 were in accordance with the established criteria. Of these, 28.12% discussed risk factors of prematurity; 37.50%, metabolic alterations and gestational dyslipidemia; 21.87%, dyslipidemic complications in preterm birth; and 12,50%, lipid metabolism, glycemic and placental transfer. Conclusion: There is a reduced adaptation of obese pregnant women to the metabolic changes of gestation. This favors dyslipidemic intercurrences in the mother, which, directly or indirectly, suggests the occurrence of premature births and high lipid transfer to the fetus. Therefore, preterm newborns, whose mothers were dyslipidemic during pregnancy, have greater risk of epicardial fat, both in early (first year of life) and in later (adult) phases of life.

Resumo Objetivo: Identificar as alterações provocadas pela dislipidemia e pela obesidade na gestação que sugerem causas de partos prematuros e o prognóstico para o recém-nascido. Método: Revisão sistemática nas bases de dados Medline, Lilacs, Embase e da biblioteca Cochrane entre os anos de 1996 e 2016. O processo de seleção ocorreu a partir dos descritores dislipidemia, gravidez, obesidade, nascimento prematuro. Um protocolo foi programado, havendo uma etapa seletiva de inclusão/exclusão das pesquisas. Resultados: Dentre os 5.789 artigos inicialmente selecionados entre março e julho de 2016, somente 32 estavam de acordo com os critérios estabelecidos. Desses, 28,12% focavam nos fatores de risco da prematuridade; 37,50%, em alterações metabólicas e dislipidemia gestacional; 21,87%, em intercorrências dislipidêmicas no parto prematuro; 12,50%, em metabolismo lipídico, glicêmico e transferências pela placenta. Conclusão: Existe uma menor adaptação da gestante obesa às mudanças metabólicas da gestação, favorecendo intercorrências dislipidêmicas na mãe, o que, direta ou indiretamente, sugere a ocorrência de partos prematuros e uma elevada transferência de lipídios para o feto. Portanto, recém-nascidos prematuros de mães dislipidêmicas durante a gravidez apresentam maior risco de desenvolver gordura epicárdica tanto na fase precoce (primeiro ano de vida) quanto na tardia (vida adulta).

Single-nucleotide polymorphisms: a perspective of cardiovascular prevention / Polimorfismos de nucleotídeo único: uma perspectiva de prevenção cardiovascular

Summary Introduction: several studies have evaluated the utilization of lipid biomarkers in an attempt to correlate them with clinical cardiovascular events. Nevertheless, the investigation of clinical conditions under specific plasmatic levels of lipoproteins for long periods presents limitations due to inherent difficulties that are related to the follow-up of individuals throughout their lives. Better understanding of the clinical response and occasional resistance to the action of hypolipidemic drugs in several clinic scenarios is also necessary. Objectives: to determine the role of evaluation of single-nucleotide polymorphisms (SNPs) related to the metabolism of lipids, and its implications in different clinical scenarios. Methods: a search of the literature in English and Spanish languages was performed in Medline, Lilacs via Bireme, IBECS via Bireme, and Cochrane databases. The expected results included information regarding plasmatic lipid profile and SNPs, cardiovascular clinical outcomes and polymorphisms related to the effectiveness of statins in the treatment of hypercholesterolemia. Results: in order to perform this analysis, 19 studies were included from a total of 89 identified citations. The evaluation of the results suggests that low plasmatic levels of LDL-c are associated with a reduction in the risk of heart attacks, although this was not observed for the rise of plasmatic levels of HDL-c. Conclusion: polymorphisms in different populations and clinical perspectives may bring important contributions for a better understanding and adequacy of plasmatic lipoproteins aiming at reducing cardiovascular risk.

Resumo Introdução: muitos estudos tem avaliado a utilização de biomarcadores lipídicos na tentativa de correlacioná-los com eventos clínicos cardiovasculares. Contudo, a investigação de condições clínicas sob níveis plasmáticos específicos de lipoproteínas por longos períodos, apresenta limitações devido às dificuldades inerentes relacionadas ao acompanhamento de indivíduos ao longo de suas vidas. Adicionalmente, há a necessidade de melhor compreensão da resposta clínica e eventual resistência da ação de drogas hipolipemiantes em diversos cenários clínicos. Objetivos: determinar o papel da avaliação de polimorfismos de nucleotídeo único (SNPs) relacionadas com o metabolismo lipídico e suas implicações em diferentes cenários clínicos. Métodos: foi realizada uma pesquisa na literatura de língua inglesa e espanhola nas bases de dados Medline, Lilacas via Bireme, IBECS via Bireme e Cochrane. Os resultados esperados incluíam informações sobre o perfil lipídico plasmático e SNPs, desfechos clínicos cardiovasculares e polimorfismos relacionadas à efetividade de estatinas quanto ao tratamento da hipercolesterolemia. Resultados: para esta análise foram incluídos 19 estudos de um total de 89 citações identificadas. Os dados resultantes e avaliados sugerem que baixos níveis plasmáticos de LDL-c estão associados com redução do risco de infarto do miocárdio o que não foi observado para o aumento nos níveis plasmáticos de HDL-c. Conclusão: os polimorfismos em diferentes populações e perspectivas clínicas podem trazer importantes contribuições para a melhor compreensão e adequação de metas de lipoproteínas plasmáticas que visem a redução de risco cardiovascular.

No association between 25-hydroxyvitamin D levels and prediabetes in Brazilian patients. A cross-sectional study / Ausência de associação entre níveis de 25-hidroxivitamina D e pré-diabetes em pacientes brasileiros. Um estudo transversal

CONTEXT AND OBJECTIVE: Several studies have evaluated the role of low 25-hydroxyvitamin D (25OHD3) in the pathogenesis of type 2 diabetes (T2DM) and have presented controversial results. The metabolic processes that culminate in T2DM begin under prediabetic conditions. Our aim was to analyze the association between 25OHD3 and glucose metabolism in individuals who were free from but at elevated risk of diabetes. DESIGN AND SETTING: Cross-sectional study at a tertiary hospital. METHODS: Anthropometric and laboratory profiles were determined in patients with one or more of the following risk factors: hypertension; body mass index (BMI) ≥ 25 kg/m2; waist circumference > 80 cm for women and > 94 cm for men; first-degree relatives with diabetes; women with large-for-gestational-age newborns or with gestational T2DM; HDL-cholesterol (high density lipoprotein) < 35 mg/dl; and triglycerides > 250 mg/dl. The patients were divided into two groups: one with prediabetes (abnormal fasting plasma glucose or oral glucose tolerance test) and the other with normal glucose (euglycemic). RESULTS: There was no statistically significant difference between the prediabetic group (n = 38) and euglycemic group (n = 15) regarding age (66.4 ± 10.6 versus 62.6 ± 9.1 years), gender (52.6 versus 73.3% female) and BMI (30.1 ± 4.61 versus 27.9 ± 4.7 kg/m2). Low serum levels of 25OHD3 were found in both groups, without any statistically significant difference between them (29.1 ± 11.8 versus 26.87 ± 9.2 ng/dl). CONCLUSION: There was no association between 25OHD3 levels and the clinical or laboratorial variables analyzed. .

CONTEXTO E OBJETIVO: Vários estudos já avaliaram o papel da 25-hidroxivitamina D (25OHD3) na patogênese do diabetes tipo 2 (DM2) e apresentaram resultados controversos. Os processos metabólicos que culminam no DM2 se iniciam no pré-diabetes. Nosso objetivo foi analisar a associação da 25OHD3 com o metabolismo glicêmico em indivíduos sem diagnóstico mas com alto risco para diabetes. TIPO DE ESTUDO E LOCAL: Estudo transversal em hospital terciário. MÉTODOS: Medidas antropométricas e laboratoriais foram determinadas em pacientes com um ou mais dos fatores de risco: hipertensão; índice de massa corpórea (IMC) ≥ 25 kg/m2; circunferência abdominal > 80 cm no sexo feminino e > 94 cm no sexo masculino; parentes de primeiro grau com diabetes; mulheres com filho nascido grande para idade gestacional ou com DM2 na gravidez; colesterol HDL (high density lipoprotein) < 35 mg/dl e triglicerídeo > 250 mg/dl. Os pacientes foram divididos em dois grupos: um com pré-diabetes (glicemia de jejum ou teste de tolerância oral à glicose alterados) e outro com glicose normal (euglicêmicos). RESULTADOS: Entre pré-diabéticos (n = 38) e euglicêmicos (n = 15) não houve diferença estatística na idade (66,4 ± 10,6 versus 62,6 ± 9,1 anos), gênero (52,6 versus 73,3% feminino) e IMC (30,1 ± 4,61 versus 27,9 ± 4,7 kg/m2). Baixos niveis séricos de 25OHD3 foram encontrados nos dois grupos, sem diferença estatística entre eles (29,1 ± 11,8 versus 26,87 ± 9,2 ng/dl). CONCLUSÃO: Não houve associação entre os níveis de 25OHD3 e as variáveis clínicas e laboratoriais analisadas. .

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Colesterol, triglicéridos y otros factores de riesgo en pacientes con edema macular diabético / Cholesterol, triglycerides and other factors of risk in patients with diabetic macular edema

La retinopatía diabética y sus complicaciones es la causa principal de disminución de la agudeza visual en la población, debido a los factores de riesgo y a un deficiente control metabólico de la enfermedad, su diagnóstico constituye un reto para los oftalmólogos en su actuar diario.Objetivo: determinar la presencia de dislipidemias y otros factores de riesgo en pacientes con edema macular diabético.Métodos: se realizó un estudio observacional descriptivo de corte transversal en pacientes con edema macular diabético que acudieron a la consulta de retina del Centro Oftalmológico Carlos J Finlay desde octubre 2011 a octubre 2012. El universo estuvo constituido por 100 pacientes y la muestra no probabilística estuvo formada por 80 pacientes que cumplieron los criterios de inclusión. Se les aplicó un formulario para recoger los datos. Los resultados se relacionaron con las siguientes variables: tiempo de evolución de la diabetes mellitus, tratamiento farmacológico, valores de colesterol y de triglicéridos, alteraciones de la microperimetría. Para la realización de la microperimetría se utilizó el protocolo automático para la mácula de 12 grados, 45 puntos maculares.Resultados: se presentaron en mayor número los pacientes con edema macular clínicamente significativo, con más de 10 años de evolución de la diabetes, los tratados con insulina y los que presentaron cifras elevadas de colesterol y triglicéridos, el mayor número de pacientes presentaron alteraciones en la microperimetría.Conclusiones: se presentaron en mayor número los pacientes con edema macular en la clasificación referida. Se demostró la estrecha relación entre edema macular diabético y factores como: el tiempo de evolución de la diabetes, el tratamiento farmacológico y los valores de colesterol y triglicéridos...

Diabetic retinopathy and its complications is the main cause of the decrease of visual acuity of people, owing to the factors of risk and to a poor metabolic control of the disease; its diagnosis is a daily challenge for ophthalmologists.Objective: to determine the presenceof dyslipemias and other factors of risk in patients with diabetic macular edema.Methods: a cross-sectional, observational, descriptive study was conducted in patients with diabetic macular edema that assisted to the consultation of retina at the Carlos J. Finlay Ophthalmologic Center from October, 2011 to October, 2012. The universe was composed of 100 patients and the non-probabilistic sample included 80 patients that matched the criteria of inclusion. The patients had to fill in a form to get information about them. The results were related to the next variables: time of evolution of the diabetes mellitus, pharmacological treatment, cholesterol and triglycerides levels, and alterations in the microperimetry. For making the microperimetry, the automatic protocol for the 12-degrees macula, 45 macular points, was used.Results: most of the patients that assisted to the consultation presented a clinically significant macular edema, with diabetes of more than ten years of evolution. Patients treated with insulin and those that presented high levels of cholesterol and triglycerides also assisted to the consultation. The greater number of patients presented alterations in the microperimetry.Conclusions: the greater number of the patients that assisted to the consultation presented macular edema in a referred classification. The close relation that exist between the diabetic macular edema and factors like the time of evolution of the diabetes, the pharmacological treatment and the cholesterol and triglycerides levels, was showed...

Efeito hipolipidêmico do suco de camu-camu em ratos / Hypolipidemic effect of camu-camu juice in rats

OBJETIVO: Este estudo teve como objetivo avaliar o potencial hipolipidêmico do suco de camu-camu (Myrciaria dubia (Kunth) McVaugh) em ratos dislipidêmicos. MÉTODOS: Foram utilizados 72 ratos (Rattus norvegicus var. albinus) machos adultos da linhagem Wistar, com peso médio de 200g. O experimento foi dividido em duas fases: indução da dislipidemia e tratamento. Para indução da dislipidemia, todos os ratos receberam ração hiperlipídica (ração comercial adicionada a 10,0% de banha suína, 1,0% colesterol e 0,1% de ácido cólico) durante 21 dias. Na fase de tratamento, 40 ratos dislipidêmicos foram divididos aleatoriamente em 5 grupos (n=8), sendo 3 deles submetidos a tratamento com diferentes concentrações de suco de camu-camu (0,4mL.kg-1, 4,0mL.kg-1 e 10mL.kg-1) por 14 dias, 1 grupo submetido a tratamento com quercetina (10mL.kg-1) e 1 grupo hiperlidêmico. Estes dois últimos foram mantidos como parâmetro, ao lado do grupo basal. Para avaliar o efeito modulador do suco de camu-camu no perfil lipídico dos ratos, foram verificadas as concentrações de triacilgliceróis, colesterol total, lipoproteína de alta intensidade e lipoproteína de baixa intensidade, no plasma, assim como os níveis de colesterol fecal e hepático.RESULTADOS: As diferentes doses de suco de camu-camu e de quercetina apresentaram efeitos moduladores do perfil lipídico, ou seja, redução de triacilgliceróis, colesterol total, excreção fecal de colesterol, bem como redução do colesterol hepático. Salienta-se que os melhores resultados foram obtidos com a concentração de 10mL.kg-1. Resultado similar foi observado quanto ao consumo de ração. CONCLUSÃO: O suco de camu-camu apresentou efeito modulador do perfil lipídico em ratos dislipidêmicos. Os resultados poderão ser utilizados como referência em futuros trabalhos acerca desse fruto amazônico.

OBJECTIVE: This study evaluated the potential hypolipidemic effect of camu-camu juice (Myrciaria dubia (Kunth) McVaugh) in dyslipidemic rats. METHODS: Seventy-two adult male Wistar rats (Rattus norvegicus var. albinus Berkenhout) with an average weight of 200g were used. The experiment was divided into two phases: induction of dyslipidemia and treatment. Dyslipidemia was induced by a high-fat diet (commercial feed plus 10.0% lard, 1.0% cholesterol and 0.1% cholic acid) given to the animals for 21 days. In the treatment phase, 40 dyslipidemic rats were randomly divided into five groups (n=8). Of these, three were subjected to different treatments with camu-camu juice: 0.4mL.kg-1, 4.0mL.kg-1 and 10mL.kg-1 for 14 days. The other two groups were kept as parameters: a basal group (normolipidemic) and a hyperlipidemic group receiving 10mL.kg-1 of quercetin (standard treatment). The potential hypolipidemic effect of camu-camu juice was assessed by the following measurements: plasma lipoproteins (triacylglycerol, total cholesterol, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol), fecal and liver cholesterol, and measurements of feed intake and body weight. RESULTS: All dosages of camu-camu juice were hypolipidemic, reducing triacylglycerol, total cholesterol, fecal cholesterol excretion and hepatic cholesterol. The best results were obtained by the 10 mL.kg-1 dosage of camu-camu juice. Rat body weight and food intake did not vary significantly during the treatment. CONCLUSION: Camu-camu juice has a hypolipidemic effect in dyslipidemic rats. These results can be used as reference for future studies on this Amazonian fruit.

Associação entre nível de atividade física e perfil bioquímico de nipo-brasileiros / Association between physical activity and biochemical profile of nipo-brazilian

Descendentes de imigrantes japoneses que vivem no Brasil apresentam alterações das concentrações plasmáticas de glicose e lipídios. Este estudo transversal teve por objetivo verificar a associação entre o perfil bioquímico e suas alterações com o nível de atividade física (AF) de nipo-brasileiros de segunda geração. Foram avaliados 371 participantes (58,8% mulheres) com idade média de 53±9 anos. Os indivíduos foram categorizados de acordo com o International Physical Activity Questionnaire (IPAQ) em baixa AF (GB), AF moderada (GM) e AF vigorosa (GV). Foram dosadas as concentrações plasmáticas de colesterol total (CT), LDL-colesterol (LDL-C), HDL-colesterol (HDL-C), triglicerídeos (TG), glicemia de jejum (GJ) e realizada avaliação antropométrica. Após verificar a normalidade dos dados (Kolmogorov-Smirnov), as variáveis foram comparadas de acordo com o sexo (t de student) e entre os níveis de AF (ANOVA one way) e as associações entre os grupos e as alterações bioquímicas (qui-quadrado). O GB representou 64% da amostra e o GV, 7%. Os homens apresentaram valores mais elevados de GJ e TG. Níveis mais altos de AF foram associados com valores reduzidos de CT e LDL-C em homens (p<0,05). Houve predominância de indivíduos com perfil lipídico alterado no GB e GM, enquanto no GV a predominância foi de normolipidêmicos. A atividade física de intensidade vigorosa e moderada não se associou com valores reduzidos de GJ e de TG, apenas o GV masculino apresentou melhor perfil lipídico. Mudanças relacionadas ao aumento da atividade física são necessárias para essa população.

Japanese immigrants descendants living in Brazil have changes in plasma lipid and glucose levels. This cross-section study aimed to verify the association between biochemical profiles and its changes, and physical activity level (PA) in Japanese-Brazilian of the second generation. We evaluated 371 subjects (58.8% women); mean age 53±9 years. Individuals were categorized according to the International Physical Activity Questionnaire (IPAQ) in low PA (GB), moderate PA (GM) and vigorous PA (GV). The plasma concentrations of the total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), fasting plasma glucose (FPG) were measured and anthropometry evaluation realized. After checking the normality data (Kolmogorov-Smirnov), the variables were compared between sexes (Student t) and between levels of PA (ANOVA One-way) and associations between groups and biochemical changes (chi-square). The GB accounted for 64% of the sample and the GV, 7%. Men showed higher values of FPG and TG. Vigorous PA were associated with reduced values of TC and LDL-C in men (p<0.05). Individuals with altered lipid profile were predominant in GB and GM, while the predominance in the GV was of normolipidemic. The vigorous and moderate physical activity were not associated with reduced values of FPG and TG, only the men GV showed better lipid profile. Changes to increase the physical activity are needed for this population.

Importancia del estudio del perfil lipídico en niños obesos / Importance of studying the lipid profile in obese children

La arterioesclerosis, es un proceso complejo y multifactorial que se inicia con la identificación de la estría lipídica a los 3 años de edad, lesión que progresa a placa fibrosa y lesión complicada en los años posteriores. La obesidad, es definida como una deposición excesiva de grasa en el cuerpo, que está asociado con consecuencias adversas para parámetros metabólicos, también consecuencias a corto y largo plazo y usualmente también con problemas psicosociales significativos y el desarrollo de enfermedades crónicas. Las dislipemias son uno conjunto de entidades que afectan al metabolismo lipídico y cuyos efectos nocivos son determinantes en el desarrollo del proceso de arteriosclerosis.

Atherosclerosis is a multifactorial complex process that begins with the identification of lipid streak at 3 years of age, injury progressing to fibrous plaque and complicated lesión in subsequent years. Obesity is defined as an excessive deposition of fat in the body, wich is associated with adverse metabolic parameters, also the short-and long-term and usually also with significant psychosocial problems and chronic disease development. The dyslipidemias are one set of entities that affect lipid metabolism and the harmful effects are crucial in the development of aterosclerosis process.

Manejo integral de las dislipidemias en niños y adolescentes: [revisión] / Integral management of dyslipidemias in children and adolescents: [review]

Las enfermedades cardiovasculares constituyen la primera causa de morbimortalidad a nivel mundial y nacional. La enfermedad arterial coronaria y periférica se encuentra íntimamente ligada a los niveles elevados de lípidos en sangre. La aterosclerosis es una enfermedad que puede iniciarse en los primeros años de vida y manifestarse con severidad en la etapa adulta, si no se realizan medidas correctivas en el paciente de riesgo. Con el objetivo de actualizar las pautas nacionales para el manejo del paciente con dislipidemia, se reunieron un grupo de investigadores venezolanos en el año 2010, a propósito del III Consenso Nacional para el Manejo del Paciente con Dislipidemia. Se presentan las conclusiones y recomendaciones del grupo de trabajo: Manejo Integral de las Dislipidemias en niños y adolescentes. Se incluyen las estrategias para prevención, recomendaciones generales para la población pediátrica, con énfasis en recomendaciones individuales para niños y adolescentes de alto riesgo.

Cardiovascular diseases are the leading cause of morbidity and mortality at global and national levels. Coronary and peripheral arterial disease is closely linked to high lipid levels in blood. Atherosclerosis is a disease that can begin in the first years of life and be clinical with severity in adult life, if you do not perform corrective action in patient at risk. With the objective of updating national guidelines for the management of Dyslipidemia patients met Venezuelan researchers in 2010 concerning III National Consensus for the Management of Patient with Dyslipidemia, then presented the conclusions and recommendations of the Working Group: Integral Management of Dyslipidemias in children and adolescents. It includes strategies for prevention, general recommendations for the pediatric population, with enphasis on high risk children and adolescents.

Estudo prospectivo, duplo cego e cruzado da Camellia sinensis (chá verde) nas dislipidemias / Estudio prospectivo, doble ciego y cruzado de la Camellia sinensis (té verde) en las dislipidemias / Prospective double-blind crossover study of Camellia sinensis (green tea) in dyslipidemias

FUNDAMENTO: Estudos epidemiológicos estabeleceram uma associação entre dislipidemias e aterosclerose. A terapia nutricional é um ponto central da estratégia preventiva em indivíduos que apresentam fatores de risco para doença aterosclerótica. OBJETIVOS: Investigar os efeitos do chá verde (Camellia sinensis) em pacientes portadores de dislipidemias. MÉTODOS: O estudo envolveu 33 pacientes, com idade entre 21 e 71 anos, que consumiam uma dieta com baixo teor de gorduras (25 por cento a 35 por cento das calorias totais e 200 mg de colesterol por dia). Foram randomizados para dois tratamentos sequenciais: cápsulas contendo 250 mg de extrato seco do chá verde ou placebo, administradas por um período total de 16 semanas, tendo cada paciente utilizado chá verde (Camellia sinensis) por oito semanas e placebo em igual período. RESULTADOS: Os valores lipídicos basais (mg/dl) foram os seguintes: HDL-colesterol 60,7 ± 7,3; colesterol total 255 ± 30,9; LDL-colesterol 158,8 ± 29,0; triglicerídeos 169,0 ± 61,3 e Apo-B 120,2 ± 18,9. As variações lipídicas médias, provocadas pelo uso do chá verde (Camellia sinensis), mostraram uma redução de 3,9 por cento (p = 0,006) nas concentrações do colesterol total e uma redução de 4,5 por cento (p = 0,026) do LDL-colesterol. A ingestão de chá verde não influenciou significativamente os níveis de HDL-colesterol, dos triglicerídeos e do Apo-B. Resultados não significativos foram observados na avaliação dos lipídeos sanguíneos (colesterol total e LDL-colesterol) com o uso do placebo. CONCLUSÃO: Foi demonstrado o efeito benéfico do chá verde (Camellia sinensis), que reduziu significativamente, em oito semanas, os níveis de colesterol total e LDL-colesterol nesse grupo de pacientes.

BACKGROUND: Epidemiological studies have established an association between dyslipidemias and atherosclerosis. Nutritional therapy is a key point in the prevention strategy for individuals who present with risk factors for atherosclerotic disease. OBJECTIVES: To investigate the effects of green tea (Camellia sinensis) in patients with dyslipidemias. METHODS: The study included 33 patients aged between 21 and 71 years who had a low-fat diet (25-35 percent of total calories and 200 mg of cholesterol per day). They were randomized for two sequential treatments: 250-mg capsules of green tea dry extract or placebo for a total period of 16 weeks; each patient received green tea (Camellia sinensis) for eight weeks and placebo for another eight weeks. RESULTS: Baseline lipid values (mg/dL) were: HDL-cholesterol 60.7 ± 7.3; total cholesterol 255 ± 30.9; LDL-cholesterol 158.8 ± 29.0; triglycerides 169.0 ± 61.3 and Apo-B 120.2 ± 18.9. Mean lipid variations induced by the use of green tea (Camellia sinensis) showed a 3.9 percent reduction (p = 0.006) in total cholesterol concentrations and a 4.5 percent reduction (p = 0.026) in LDL-cholesterol. The intake of green tea did not significantly influence HDL-cholesterol, triglyceride, and Apo-B levels. Non-significant results were found in the assessment of blood lipids (total cholesterol and LDL-cholesterol) with the use of placebo. CONCLUSION: A beneficial effect of green tea (Camellia sinensis) was demonstrated, with a significant reduction of total cholesterol and LDL-cholesterol levels in eight weeks, in the patients studied.

FUNDAMENTO: Estudios epidemiológicos establecieron una asociación entre dislipidemias y aterosclerosis. La terapia nutricional es un punto central de la estrategia preventiva en individuos que presentan factores de riesgo para enfermedad aterosclerótica. OBJETIVO: Investigar los efectos del té verde (Camellia sinensis) en pacientes portadores de dislipidemias. MÉTODOS: El estudio implicó a 33 pacientes, con edad entre 21 y 71 años, que consumían una dieta con bajo tenor graso (el 25 por ciento al 35 por ciento de las calorías totales y 200mg de colesterol por día). Se randomizaron para dos tratamientos secuenciales: cápsulas conteniendo 250mg de extracto seco del té verde o placebo, administradas por un período total de 16 semanas, habiendo cada paciente utilizado té verde (Camellia sinensis) por ocho semanas y placebo en igual período. RESULTADOS: Los valores lipídicos basales (mg/dl) fueron los siguientes: HDL-colesterol 60,7 ± 7,3; colesterol total 255 ± 30,9; LDL-colesterol 158,8 ± 29,0; triglicéridos 169,0 ± 61,3 y Apo-B 120,2 ± 18,9. Las variaciones lipídicas promedios, provocadas por el uso del té verde (Camellia sinensis), evidenciaron una reducción de un 3,9 por ciento (p = 0,006) en las concentraciones del colesterol total y una reducción de un 4,5 por ciento (p = 0,026) del LDL-colesterol. La ingestión de té verde no influenció significativamente los niveles de HDL-colesterol, de los triglicéridos y de la Apo-B. Resultados no significativos se observaron en la evaluación de los lípidos sanguíneos (colesterol total y LDL-colesterol) con el empleo del placebo. CONCLUSIÓN: Se evidenció el efecto benéfico del té verde (Camellia sinensis), que redujo significativamente, en ocho semanas, los niveles de colesterol total y LDL-colesterol en ese grupo de pacientes.