Maria Inês de Albuquerque Wilasco

Ghrelin, leptin and insulin in healthy children: Relationship with anthropometry, gender, and age distribution

OBJECTIVES This study aimed to establish the relationship between total ghrelin, acyl ghrelin, des-acyl ghrelin, leptin, and insulin with anthropometry, gender, and age distribution in healthy children. RESULTS Data from 111 healthy children aged 4 months to 10 years were studied. All the participants underwent a pre-study screening clinical evaluation and were separated in 3 age groups. All had blood collected to assay. Anthropometric parameters were measured according to World Health Organization. In order to determine the correlation between dependent and independent variables, a multiple linear regression analysis was used. Overall median age of subjects was 60.0 months. After multiple regression analysis, correlation between total ghrelin, acyl ghrelin and des-acyl ghrelin remained significant with age. Correlation between leptin values and age, body mass index-for-age ratio, height-for-age ratio, and female gender remained significant. There was no significant correlation between insulin and ghrelin, and between insulin and leptin in all age groups. There was an inverse significant correlation between total ghrelin and des-acyl ghrelin with leptin in the whole group. CONCLUSIONS Ghrelin showed an inverse correlation with age and leptin showed a direct correlation with anthropometric parameters and female gender in healthy children. Insulin did not show any correlation.

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease.

AIM To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. METHODS We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS The median (25(th)-75(th) centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.

IL-6, TNF-α, IL-10, and nutritional status in pediatric patients with biliary atresia

OBJECTIVES The objective of the present study is to evaluate whether IL-6, TNF-α, IL-10 are associated with nutritional status in patients with cirrhosis secondary to biliary atresia and compare to healthy controls. METHODS The parameters used for nutritional assessment were the standard deviation scores of height-for-age and of triceps skinfold thickness-for-age. The severity of cirrhosis was evaluated using the Child-Pugh score and PELD/MELD. Serum cytokines were measured using Cytometric Bead Array flow cytometry. RESULTS IL-6, TNF-α, and IL-10 were significantly higher in the cirrhosis group when compared with the control group (2.4 vs. 0.24 (p<0.001), 0.21 vs. 0.14 (p=0.007), and 0.65 vs. 0.36 (p=0.004), respectively. IL-6 and IL-10 were positively correlated with disease severity (0.450 [p=0.001] and 0.410; [p=0.002], respectively). TNF-α did not show a significant correlation with disease severity (0.100; p=0.478). Regarding nutritional evaluation, IL-6 was negatively correlated with the standard deviation score of height-for-age (-0.493; p<0.001) and of triceps skinfold thickness-for-age (-0.503; p<0.001), respectively. IL-10 exhibited a negative correlation with the standard deviation score of height-for-age (-0.476; p<0.001) and the standard deviation score of triceps skinfold thickness-for-age (-0.388; p=0.004). TNF-α did not show any significance in both anthropometric parameters (-0.083 (p=0.555) and -0.161 (p=0.253). CONCLUSION The authors suggest that, in patients with cirrhosis secondary to biliary atresia, IL-6 could be used as a possible supporting biomarker of deficient nutritional status and elevated IL-10 levels could be used as a possible early-stage supporting biomarker of deteriorating nutritional status.

Avaliação nutricional em crianças e adolescentes com cirrose: estudo transversal de duas séries

Introducao : A cirrose caracteriza-se por uma alteracao cronica do parenquima hepatico que frequentemente leva a desnutricao em criancas e adolescentes. A intervencao nutricional deve ser feita precocemente, o que requer um cuidadoso acompanhamento desses pacientes. Objetivos : Comparar os resultados da avaliacao nutricional de criancas e adolescentes cirroticos realizada em dois periodos de tempo distintos. Metodos : Foram utilizados bancos de dados oriundos de duas pesquisas conduzidas com pacientes pediatricos com cirrose. Apos a aplicacao de criterios de inclusao e exclusao, 67 criancas e adolescentes foram avaliados em duas series com intervalo de aproximadamente uma decada entre elas. As duas series tiveram as variaveis antropometricas estatura para idade (E/I) e dobra cutânea tricipital para idade (DCT/I) avaliadas de acordo com os padroes da Organizacao Mundial de Saude. A gravidade da doenca foi avaliada pelos modelos Pediatric End-stage Liver Disease (PELD)/ Model for End-stage Liver Disease (MELD) e pelo escore Child-Pugh. O nivel de significância foi estabelecido em 5%. Resultados : Os resultados da avaliacao do estado nutricional dos pacientes nas duas series nao mostraram diferenca estatisticamente significativa. Na serie 1, 22,6% dos pacientes apresentaram desnutricao, e 27,8% na serie 2 (p = 0,955). Conclusoes : Podemos concluir que nas duas series avaliadas, separadas por aproximadamente uma decada, o percentual de desnutricao e a gravidade da cirrose se mantiveram estaveis. Palavras-chave: Avaliacao nutricional, crianca, adolescente, cirrose.

Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia

Background: The nutritional status in patients with cirrhosis is not so easy to assess properly. Considering the relationship between brain-derived neurotrophic factor (BDNF) and energy homeostasis, the main aim of this study was to evaluate the concentration of BDNF in children and adolescents with cirrhosis due to biliary atresia (BA) and correlate it with their nutritional status. Methods: Fifty-three children and adolescents with cirrhosis due to BA and 33 healthy controls were enrolled in this study. Nutritional status was evaluated using anthropometric parameters, and serum BDNF was measured by ELISA. Spearman coefficient was used to evaluate the correlation between variables. Results: In the cirrhosis group, 28.8% were undernourished and in the control group, 100% were well-nourished. BDNF median values for the control and cirrhosis group were 28.5 and 9.0 pg/ml respectively. BDNF and platelets were positively associated with both Standard Deviation Score (SDS) for height-for-age ratio and SDS for triceps skinfold thickness-for-age ratio. Conclusions: Considering these associations, BDNF may be an indirect biomarker of nutritional status in children and adolescents with chronic liver disease. Further studies must be conducted to clarify the role of BDNF in this population.

The role of intestinal microbiota in energetic metabolism : new perspectives in combating obesity

The knowledge that the composition of intestinal microbiota is different in lean and obese humans indicates that the microbiota plays an important role in the pathophysiology of obesity. Studies show that diet composition promotes the modification of intestinal bacterial species, favoring the increase of energy extraction from the diet, insulin resistance and obesity. Unbalanced diets, with overload fat and low fiber content, lead to increased Firmicutes and Proteobacteria phyla favoring dysbiosis, endotoxemia and inflammation. The use of probiotics, prebiotics and symbiotics, in order to modulate the composition of intestinal microbiome, may be a promising therapy for the reduction of the metabolic complications of obesity; however, further studies should be conducted to establish which probiotic species are suitable to help in the treatment of obesity.

M1732 Ghrelin and Leptin in Children and Adolescents With Cirrhosis

Introduction: Anorexia and hypermetabolism are a problem of paramount importance in children with cirrhosis. Plasma levels of both leptin and ghrelin are altered in patients with starvation and chronic diseases associated with anorexia. Ghrelin has an important role on feeding and weight homeostasis. Aim: We aimed to assess ghrelin and leptin levels in cirrhotic children and adolescents in comparison with controls. Methods: Forty children with cirrhosis (biliary atresia as etiology in 67.5%) aged between 3.7 and 188.7 months, 50% male, were evaluated, 50% were Child-Pugh A; 40%, B and 10%, C. Other 40 healthy children matched for sex and age, taken as controls, were also evaluated. Blood samples were collected at least after 3-hours fasting. Fasting leptin and acylated ghrelin levels were measured using a newly developed ELISA kit (Linco Research, St Charles-MI, USA). Body composition including body mass index (BMI), body fat mass and height for age were determined and classified according to WHO 2009 and Frisancho 2008 standard reference. All controls were eutrophic as well as 77.5% of cirrhotic patients. Other cirrhotics were either undernourished (21.3%) or overweighed (1.3%). Results: Ghrelin and leptin in both groups did not correlate with sex (P=0.023). Median values (25-75 centile) of acylated ghrelin were significantly lower in cirrhotics than in healthy controls [140.3 (93.9-269.7) pg/mL vs 277.8 (209.9-557.8) pg/mL, P=0.003]. Median values of total ghrelin and desacyl ghrelin of children with cirrhosis were 913.4 pg/mL (760.8-1443.7) and 1397.8 pg/mL (815.27-2047) respectively. Median values of leptin were not significantly different between cirrhotics and controls (P=0,26)]. From the cirrhotic group there was a significant difference between undernourished and well-nourished pactients [1.45ng/mL (0.66-1.88) 2.68 ng/mL (1.31-4.38)], P=0.023. Median values of Child-Pugh C were significantly lower than B and A [0.67 (0.17-1.11) ng/mL; 1.83 (1.24-4.04) ng/mL; 1.88 (0.67-3.67) ng/mL], P=0.033. Conclusions: Cirrhotic children showed lower plasma levels of acylated ghrelin compared with controls. This might be representative of the anorexia that consequently contributes to the malnourishment and illness severity of cirrhotic patients.