Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen-level dependent response to glucose ingestion.

OBJECTIVE: In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS: Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS: Children with obesity (N = 11) had longer T2 relaxation times, consistent with gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION: Imaging signs of hypothalamic gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

Sagittal abdominal diameter resembles waist circumference as a surrogate marker of insulin resistance in adolescents-Brazilian Metabolic Syndrome Study.

OBJECTIVE: To evaluate the association of the sagittal abdominal diameter (SAD) with insulin resistance (IR) and metabolic syndrome (MetS) components, and to compare SAD with waist circumference (WC). SUBJECTS/METHODS: This was a multicenter, cross-sectional study of 520 adolescents (10- to 18-years old). IR was assessed using the homeostasis model assessment of IR (HOMA-IR) and the hyperglycaemic clamp (n = 76). RESULTS: SAD and WC were positively correlated with HOMA-IR (r = 0.637 and r = 0.653) and inversely correlated with the clamp-derived insulin sensitivity index (ISI) (r = -0.734 and r = -0.731); P < .001. In the multivariable linear regression analysis, SAD was positively associated with HOMA-IR (B = 0.046 ± 0.003) and inversely associated with the clamp-derived ISI (B = -0.084 ± 0.009) after adjusting for sex, age, and Tanner's stages (P < .001). When WC replaced the SAD, it was positively associated with HOMA-IR (B = 0.011 ± 0.001) and inversely associated with the clamp-derived ISI (B = -0.018 ± 0.002); P < .001. The values of the areas under the curves (AUC) were 0.823 and 0.813 for SAD and WC, respectively. In Bland-Altman analysis, there were agreement between both, SAD and WC, with the clamp-derived ISI (mean = 0.00; P > .05). The SAD and WC were positively associated with blood pressure, triglycerides, and uric acid, and inversely associated with high-density lipoprotein (HDL)-cholesterol after adjusting for sex, age, and Tanner's stages. CONCLUSION: The SAD was associated with IR and MetS components, with a good discriminatory power for detecting IR. When compared to WC, SAD showed equivalent results.

Adiposity and family history of type 2 diabetes in an admixed population of adolescents: Associations with insulin sensitivity, beta-cell function, and hepatic insulin extraction in BRAMS study.

AIMS: Insulin resistance and beta-cell dysfunction manifest differently across racial/ethnic groups, and there is a lack of knowledge regarding the pathophysiology of type 2 diabetes mellitus (T2DM) for ethnically admixed adolescents. This study aimed to investigate the influence of adiposity and family history (FH) of T2DM on aspects of insulin sensitivity, beta-cell function, and hepatic insulin extraction in Brazilian adolescents. METHODS: A total of 82 normoglycemic adolescents were assessed. The positive FH of T2DM was defined as the presence of at least one known family member with T2DM. The hyperglycemic clamp test consisted of a 120-min protocol. Insulin secretion and beta-cell function were obtained from C-peptide deconvolution. Analysis of covariance considered pubertal stage as a covariate. RESULTS: Both lean and overweight/obese adolescents had similar glycemic profiles and disposition indexes. Overweight/obese adolescents had about 1/3 the insulin sensitivity of lean adolescents (1.1 ±â€¯0.2 vs. 3.4 ±â€¯0.3 mg·kg·min·pmol ∗ 1000), which was compensated by an increase around 2.5 times in basal (130 ±â€¯7 vs. 52 ±â€¯10 pmol·l·min) and total insulin secretion (130,091 ±â€¯12,230 vs. 59,010 ±â€¯17,522 pmol·l·min), and in the first and second phases of insulin secretion; respectively (p < 0.001). This increase was accompanied by a mean reduction in hepatic insulin extraction of 35%, and a 2.7-time increase in beta-cell glucose sensitivity (p < 0.05). The positive FH of T2DM was not associated with derangements in insulin sensitivity, beta-cell function, and hepatic insulin extraction. CONCLUSIONS: In an admixed sample of adolescents, the hyperglycemic clamp test demonstrated that adiposity had a strong influence, and FH of T2DM had no direct influence, in different aspects of glucose metabolism.

Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma / Espirometria e capnografia volumétrica na avaliação da função pulmonar de indivíduos obesos e eutróficos sem asma

Abstract Objective: To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Methods: Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. Results: At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV1/FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p < 0.05). Volumetric capnography showed that obese individuals had a higher volume of produced carbon dioxide and alveolar tidal volume (p < 0.05). Additionally, the associations between dead space volume and tidal volume, as well as phase-3 slope normalized by tidal volume, were lower in healthy subjects (p < 0.05). These data suggest that obesity does not alter ventilation homogeneity, but flow homogeneity. After subdividing the groups by age, a greater difference in lung function was observed in obese and healthy individuals aged >11 years (p < 0.05). Conclusion: Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV1/FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes.

Resumo Objetivo: Analisar e comparar a função pulmonar de crianças e adolescentes obesos e eutróficos saudáveis, sem asma, pela espirometria e capnografia volumétrica. Métodos: Estudo transversal com 77 indivíduos (38 obesos) entre cinco e 17 anos. Todos fizeram espirometria e capnografia volumétrica. Os obesos repetiram as avaliações após o uso de broncodilatador. Resultados: Na avaliação da espirometria, os indivíduos obesos, quando comparados com o grupo controle, apresentaram menores valores no volume expiratório forçado no primeiro segundo pela capacidade vital forçada (VEF1/CVF) e nos fluxos expiratórios a 75% da CVF e entre 25-75% da mesma (p < 0,05). A capnografia volumétrica demonstrou que os obesos apresentam maior volume produzido de dióxido de carbono e volume corrente alveolar (p < 0,05). Além disso, a relação entre o volume espaço morto e volume corrente, bem como o slope da fase 3 normalizado pelo volume corrente, foi menor nos indivíduos saudáveis (p < 0,05). Esses dados sugerem que a obesidade não altera a homogeneidade da ventilação, mas sim dos fluxos. Ao subdividir os grupos por idade, foi observada maior diferença na função pulmonar entre indivíduos obesos e saudáveis na faixa acima de 11 anos (p < 0,05). Conclusão: Mesmo sem o diagnóstico de asma por critérios clínicos e sem resposta ao uso de broncodilatador, os indivíduos obesos apresentaram menores valores no VEF1/CVF e nos fluxos expiratórios forçados, o que indica a presença de processo obstrutivo. A capnografia volumétrica indicou nos indivíduos obesos maior volume corrente alveolar, sem alterações na homogeneidade da ventilação, o que sugere alteração nos fluxos, sem comprometimento dos volumes pulmonares.

Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

OBJECTIVE: To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. METHODS: Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. RESULTS: At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV1/FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p<0.05). Volumetric capnography showed that obese individuals had a higher volume of produced carbon dioxide and alveolar tidal volume (p<0.05). Additionally, the associations between dead space volume and tidal volume, as well as phase-3 slope normalized by tidal volume, were lower in healthy subjects (p<0.05). These data suggest that obesity does not alter ventilation homogeneity, but flow homogeneity. After subdividing the groups by age, a greater difference in lung function was observed in obese and healthy individuals aged >11 years (p<0.05). CONCLUSION: Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV1/FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes.

Avaliaçäo do estado nutricional e do crescimento de crianças e adolescentes com insuficiencia renal crônica / Nutritional evaluation condition and the growth of the children and adolescent it chronic renal failure

Com o objetivo de avaliar o estado nutrticional de 43 pacientes(23M/20F), com idade de 1,6 a 20 anos, com insuficiencia renal crônica (IRC) acompanhados no Ambulatório de Nefrologia Pediátrtica da FCM da Unicamp, estudou-se o escore z dos indicadores altura/idade (A/I), peso/idade (P/I) e peso/altura (P/A). O clearance de creatininavariou de 0 a 46 ml/min/1,73 metros quadrados, sendo a mediana de 8,00. Encontram-se 41,9 poecento com escore z de A/I abaixo de -3,0 e 60,5 porcento abaixo de -2,0, e para o indicador P/A, apenas, um menor que -2,0. Esta distribuiçäo muito comprometida para a A/I e praticamente normal para P/A demonstra um estado nutricional bom, com repercussäo negativa sobre a estatura decorrente da longa duraçäo da doença. Para determinar quais fatores estariam associados com o comprometimento da estatura, foram avaliados parâmetros socioeconômicos (renda familiar per capita e escolaridade materna), clínicos (idade, sexo, raça,idade ao diagnóstico IRC, tempo de IRC, diagnóstico etiológico e tratamento) e laboratoriais (clearance de creatinina, hemoglobina, cálcio, fósforo inorgânico, fosfatase alcalina, pH e bicarbonato) em relaçäo ao indicador A/I. A distribuiçäo dos escores z de A/I apresentou diferença estatísticamente significante em relaçäo ao sexo e a etiologia, com maior comprometimento no sexo masculino e nos pacientes com cistinose.. A cistinose teria maior impacto no ccrescimento por ser uma patologia congênita com graves distúrbios metabólicos.(au)