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Context Congenital adrenal hyperplasia (CAH) patients have potential normal longevity. However, a greater risk for cardiovascular disease has been reported. Insulin resistance and hyperinsulinemia have been described in CAH patients, whereas the prevalence of overt type 2 diabetes is not higher in CAH than in normal population. Objective To examine the contributions of insulin secretion and of hepatic insulin clearance to compensatory hyperinsulinemia in young insulin-resistant adults with classic CAH due to 21-hydroxylase deficiency (21-OHD). Design Cross-sectional. Setting University outpatient clinics. Methods Fifty-one participants: 21 controls, and 30 CAH (15 virilizing and 15 salt-wasting phenotypes), female/male (33/18), age (mean [SD]): 24.0 (3.6) years, body mass index: 24.6 (4.9)kg/m2 with normal glucose tolerance, were submitted to a hyperglycemic clamp study. Main Outcome Measures Insulin sensitivity, beta cell function, and hepatic insulin clearance using appropriate modeling. Results We found an increased insulin resistance in 21-OHD. The systemic hyperinsulinemia (posthepatic insulin delivery) was elevated in CAH patients. No increases were observed in insulin secretory rate (beta cell function) in the first phase or during the hyperglycemic clamp. The increase in insulin concentrations was totally due to a ~33% reduction in insulin clearance. Conclusion 21-OHD nonobese subjects have reduced insulin sensitivity and beta cell response unable to compensate for the insulin resistance, probably due to overexposure to glucocorticoids. Compensatory hyperinsulinemia is most related with reduced hepatic insulin clearance. The exclusive adaptation of the liver acts as a gating mechanism to regulate the access of insulin to insulin-sensitive tissues to maintain glucose homeostasis.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo Background: Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated. Objectives: To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance. Methods: This was a cross-sectional study of 56 adolescents (aged 10–18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis. Results: In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR. Conclusions: The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy. Background: Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated. Objectives: To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance. Methods: This was a cross-sectional study of 56 adolescents (aged 10–18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis. Results: In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR. Conclusions: The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.

Orientadores: Bruno Geloneze Neto, Ana Carolina Junqueira Vasques Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: Adiposidade e história familiar de diabetes tipo 2 em uma população de adolescentes misturados: associações com sensibilidade à insulina, função de células beta e extração hepática de insulina no estudo Brazilian Metabolic Syndrome Study (BRAMS). Introdução e Objetivos: A resistência à insulina e a disfunção de células beta têm manifestações diferentes entre os grupos raciais / étnicos e há falta de conhecimento sobre a fisiopatologia do diabetes mellitus tipo 2 (DM2) em adolescentes com etnia mista. O objetivo deste estudo foi investigar a influência da adiposidade e história familiar no DM2 sobre aspectos da sensibilidade à insulina, função das células beta e extração hepática de insulina em adolescentes brasileiros. Métodos: foram avaliados 82 adolescentes normoglicêmicos. A HF positiva do DM2 foi definida como a presença de pelo menos um familiar com DM2. O teste de clamp hiperglicêmico consistiu em um protocolo de 120 minutos. A secreção de insulina e a função das células beta foram obtidas a partir da deconvolução do peptídeo-C. Análise de covariância considerada estágio puberal como covariável. Resultados: Tanto os adolescentes magros quanto os com sobrepeso / obesidade apresentaram perfil glicêmico e índice de disposição semelhantes. Adolescentes com sobrepeso / obesidade tinham cerca de 1/3 da sensibilidade à insulina de adolescentes magros (1,1 ± 0,2 vs. 3,4 ± 0,3 mg.kg.min.pmol * 1000), o que foi compensado por um aumento de 2,5 vezes na basal (130 ± 7 x 52 ± 10 pmol.l.min) e secreção total de insulina (130091 ± 12230 vs. 59010 ± 17522 pmol.l.min) e na primeira e segunda fases da secreção de insulina; respectivamente (p

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).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).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.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.

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.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.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 ± 0.2 vs. 3.4 ± 0.3 mg·kg·min·pmol ∗ 1000), which was compensated by an increase around 2.5 times in basal (130 ± 7 vs. 52 ± 10 pmol·l·min) and total insulin secretion (130,091 ± 12,230 vs. 59,010 ± 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.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.

OBJECTIVE: To evaluate the correlation between neck circumference and insulin resistance and components of metabolic syndrome in adolescents with different adiposity levels and pubertal stages, as well as to determine the usefulness of neck circumference to predict insulin resistance in adolescents.METHODS:Cross-sectional study with 388 adolescents of both genders from ten to 19 years old. The adolescents underwent anthropometric and body composition assessment, including neck and waist circumferences, and biochemical evaluation. The pubertal stage was obtained by self-assessment, and the blood pressure, by auscultation. Insulin resistance was evaluated by the Homeostasis Model Assessment-Insulin Resistance. The correlation between two variables was evaluated by partial correlation coefficient adjusted for the percentage of body fat and pubertal stage. The performance of neck circumference to identify insulin resistance was tested by Receiver Operating Characteristic Curve.RESULTS: After the adjustment for percentage body fat and pubertal stage, neck circumference correlated with waist circumference, blood pressure, triglycerides and markers of insulin resistance in both genders.CONCLUSIONS: The results showed that the neck circumference is a useful tool for the detection of insulin resistance and changes in the indicators of metabolic syndrome in adolescents. The easiness of application and low cost of this measure may allow its use in Public Health services. OBJETIVO:Evaluar la correlación de la circunferencia del cuello con resistencia a la insulina y con los componentes del síndrome metabólico en adolescentes con distintos niveles de adiposidad y estadios puberales, así como determinar la utilidad de la circunferencia del cuello como un parámetro en la predicción de resistencia a la insulina en adolescentes.MÉTODOS: Estudio transversal en el que se evaluó a 388 adolescentes de ambos sexos, de los 10 a los 19 años. Los adolescentes fueron sometidos a evaluación antropométrica y de composición corporal, incluyendo circunferencias del cuello y de la cintura, y la evaluación bioquímica. El estadio puberal se obtuvo mediante autoevaluación y la presión arterial, por el método de ausculta. Se evaluó la resistencia a la insulina por el Homeostasis Model Assessment-Insulin Resistence. La correlación entre dos variables fue evaluada con el coeficiente de corrrelación parcial ajustado para el porcentaje de grasa corporal y el estadio puberal. El desempeño de la circunferencia del cuello para identificar resistencia a la insulina fue evaluado por la Receiver Operating Characteristic Curve y se consideró p

This study aimed to identify cutoff points for detecting hypertriglyceridemic waist phenotype (HTWP) in adolescents and to investigate the association of the HTWP with insulin resistance (IR) and metabolic syndrome components.A multicentric cross-sectional study of 861 adolescents (10-19 years of age, 504 girls) was conducted. Pubertal stage, anthropometric, and laboratory parameters were assessed. IR was assessed by Homeostasis Model Assessment for Insulin Resistance (HOMA1-IR) index and hyperglycemic clamp (n = 80). HTWP was defined by the presence of increased plasma triglycerides (TGs) and increased waist circumference (WC) according to cutoff points obtained in ROC curve analysis given the HOMA1-IR index as a reference method.Cutoffs for WC and TGs, with a higher sum of sensitivity (S) and specificity (E), were, respectively:84 cm (S:65.1%, E:71.9%) and87 mg/dL (S:65.1%, E:73.4%) in pubertal girls;88.5 cm (S:80.2%, E:60.2%) and78 mg/dL (S:60.5%, E:53.2%) in postpubertal girls;94 cm (S:73.1%, E:83.1%) and79 mg/dL (S:61.5%, E:60.2%) in pubertal boys; and99 cm (S:81.3%, E:78.7%) and86 mg/dL in postpubertal boys (S:68.1%, E:60.7%). HTWP frequency was 27.5%. In the phenotype presence, after adjustment for age and pubertal stage, blood pressure and fasting glucose levels were elevated and high-density lipoprotein cholesterol was lower (p 0.001). Adolescents with the HTWP showed more IR, evaluated both by the HOMA1-IR and by the clamp test (p 0.003).The findings suggest HTWP as an IR status in adolescents. Cutoff point standardization for gender and pubertal stage, combined with the ease of application of the method, may allow their use for screening adolescents who would most benefit from lifestyle changes.

OBJETIVO: A asma e a obesidade estão entre as maiores causas de morbidade na infância e adolescência. A obesidade precoce aumenta as chances de doenças crônicas degenerativas no adulto. Embora a concomitância de ambas as situações clínicas vem sendo demonstrada em vários estudos, os mecanismos intrínsecos dessa associação ainda são pouco conhecidos. Portanto, o objetivo deste artigo foi revisar os principais trabalhos sobre a associação de obesidade e asma e verificar se existe relação de causa e efeito entre ambas. FONTES DOS DADOS: Revisão sistemática baseada em bases de dados indexadas MEDLINE (PubMed) e SciELO. Foram revisados artigos originais (transversal, caso-controle e prospectivo) e meta-análises publicados no período de janeiro de 1998 a janeiro de 2008. Foram pesquisados estudos divulgados em língua inglesa, espanhola e portuguesa. SÍNTESE DOS DADOS: Embora existam muitos estudos sobre as crescentes prevalências da asma e da obesidade, poucos estabelecem relações de causa e efeito entre ambas. Os mecanismos fisiopatológicos e os fatores envolvidos nesse processo ainda são pouco conhecidos. CONCLUSÃO: O rigor metodológico em estudos futuros deverá buscar respostas para melhor entender se existe associação entre asma e obesidade, ou se a relação entre ambas as doenças é coincidência.

OBJETIVO: Neste trabalho foi desenvolvido estudo transversal com o objetivo de verificar a prevalência da amamentação em 1 708 crianças menores de dois anos em Campinas, São Paulo. MÉTODOS: As informações sobre idade, sexo, serviço de saúde utilizado e alimentação foram obtidas por entrevistas com mães ou responsáveis durante a Campanha de Multivacinação de 2001. A amamentação foi classificada como exclusiva, predominante (incluindo outros líquidos, exceto leites), complementar (incluindo outros alimentos e/ou leites) e total (soma de exclusivo, predominante e complementar). RESULTADOS: A análise demonstrou que a mediana de amamentação exclusiva foi de 68 dias e a de amamentação total foi de 6,4 meses. No primeiro semestre de vida, 38,1% das crianças estavam em amamentação exclusiva; 23,0% em predominante e 14,9% em complementar. No segundo semestre, 36,5% das crianças recebiam leite materno; no terceiro 26,4% e no quarto 13,9%. Crianças usuárias dos serviços públicos e das unidades locais de saúde apresentaram menor risco de desmame do que as usuárias dos serviços privados e de serviços não locais (pOBJECTIVE: A cross-sectional survey was developed aiming to identify the prevalence of breastfeeding among children aged 0-2 years living in Campinas, Sao Paulo state, Brazil. METHODS: Data on age, sex, health care service used and feeding were obtained by interviewing the mothers or caregivers of 1,708 children during the National Immunization Campaign in 2001. Breastfeeding was classified as exclusive, predominant (including others liquids, except milks), complementary (including others foods and/or others milks) and total (sum of exclusive, predominant and complementary). RESULTS: The median exclusive breastfeeding was 68 days and median total breastfeeding was 6.4 months. In the first semester of life, 38.1% of the children were exclusively breastfed, 23.0 predominantly and 14.9% complementary breastfed. In the second semester, 36.5% of the children were breastfed, in the third 26.4% and in the fourth semester 13.9%. Children who used public and local health care services were less likely to be weaned than the users of private and non-local health care services (p

The association between short sleep duration and decreased insulin sensitivity in adolescents has been described. However, to our knowledge, no studies have investigated this association measuring insulin sensitivity by the hyperglycemic clamp technique.To compare the distributions of parameters of insulin resistance in adolescents with sleep deprivation vs adequate sleep, and to investigate the association between sleep deprivation and insulin sensitivity.Cross-sectional multicenter study using data from the Brazilian Metabolic Syndrome Study conducted from June 29, 2011, to December 3, 2014, at an obesity outpatient clinic at the University of Campinas and public schools, with a convenience sample of 615 adolescents aged 10 to 19.9 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for age and sex at the fifth percentile or higher. A subsample of 81 adolescents underwent the hyperglycemic clamp technique.The self-reported sleep duration was used to classify the population into 2 groups: adolescents with sleep deprivation (8 hours/night) and adolescents with adequate sleep (≥8 hours/night). Insulin sensitivity was assessed using the hyperglycemic clamp technique.Among the 615 adolescents (56.3% female; median age, 15.9 years [interquartile range, 12.9-17.8 years]) included in the sample, the mean (SD) sleep duration was 7.9 (1.7) hours/night. The adolescents with sleep deprivation (n = 257) compared with those with adequate sleep (n = 358) had a higher median (interquartile range) age (17.0 [15.4-18.3] vs 14.1 [11.8-16.9] years), BMI (25.0 [21.2-29.3] vs 23.1 [19.5-27.6]), waist circumference (83.0 [73.5-95.4] vs 79.0 [68.5-91.0] cm), sagittal abdominal diameter (17.9 [15.8-20.8] vs 17.0 [15.0-19.8] cm), neck circumference (35.2 [33.0-38.0] vs 33.0 [30.0-35.5] cm), uric acid level (4.9 [4.0-5.8] vs 4.5 [3.7-5.5] mg/dL), and white blood cell count (7000 [5900-8200] vs 6600 [5600-7800] cells/μL) (all P .05). Moreover, the adolescents with sleep deprivation had a lower median (interquartile range) insulin sensitivity index compared with those with adequate sleep (0.10 [0.05-0.21] vs 0.21 [0.09-0.33] mg · kgfat-free mass-1 · min-1 · mU/L × 100, respectively; difference, -0.01; 95% CI, -0.01 to -0.00; P = .02). After controlling for age and sex in the multivariate regression model, sleep deprivation remained an independent predictor for those variables. In the sleep deprivation group, BMI and central distribution of fat were higher in all categories of adiposity.Sleep deprivation (8 hours of sleep per night) is associated with centripetal distribution of fat and decreased insulin sensitivity in adolescents. Therefore, investigations of sleep duration and sleep quality in adolescents should be included in clinical practice to promote, through health education, the eradication of the health risks associated with sleep restriction.

OBJETIVO: A asma e a obesidade estão entre as maiores causas de morbidade na infância e adolescência. A obesidade precoce aumenta as chances de doenças crônicas degenerativas no adulto. Embora a concomitância de ambas as situações clínicas vem sendo demonstrada em vários estudos, os mecanismos intrínsecos dessa associação ainda são pouco conhecidos. Portanto, o objetivo deste artigo foi revisar os principais trabalhos sobre a associação de obesidade e asma e verificar se existe relação de causa e efeito entre ambas. FONTES DOS DADOS: Revisão sistemática baseada em bases de dados indexadas MEDLINE (PubMed) e SciELO. Foram revisados artigos originais (transversal, caso-controle e prospectivo) e meta-análises publicados no período de janeiro de 1998 a janeiro de 2008. Foram pesquisados estudos divulgados em língua inglesa, espanhola e portuguesa. SÍNTESE DOS DADOS: Embora existam muitos estudos sobre as crescentes prevalências da asma e da obesidade, poucos estabelecem relações de causa e efeito entre ambas. Os mecanismos fisiopatológicos e os fatores envolvidos nesse processo ainda são pouco conhecidos. CONCLUSÃO: O rigor metodológico em estudos futuros deverá buscar respostas para melhor entender se existe associação entre asma e obesidade, ou se a relação entre ambas as doenças é coincidência. OBJECTIVE: Asthma and obesity are among the major causes of morbidity in childhood and adolescence. Early obesity increases the chances of chronic degenerative diseases in adults. Although the concomitance or both clinical situations are being demonstrated in various studies, the intrinsic mechanisms of this association are still very little known. Therefore, the objective of this article was to review the main studies on the association of obesity and asthma and check if there is a cause-effect relation between them. SOURCES: Systematic review based on indexed data bases MEDLINE (PubMed) and SciELO. Original articles (cross-sectional, case-control, and prospective studies) and meta-analysis published in the period that ranges from January 1998 to January 2008 were reviewed. Studies published in English, Spanish, and Portuguese were researched. SUMMARY OF THE FINDINGS: Although there are various studies on growing prevalence of asthma and obesity, few of them establish cause-effect relations between them. Physiopathological mechanisms and factors involved in this process are still little known. CONCLUSION: Methodological rigor in future studies must seek for answers to better understand if there is association between asthma and obesity or if the relationship between both diseases is a coincidence.

OBJETIVO: Neste trabalho foi desenvolvido estudo transversal com o objetivo de verificar a prevalência da amamentação em 1 708 crianças menores de dois anos em Campinas, São Paulo. MÉTODOS: As informações sobre idade, sexo, serviço de saúde utilizado e alimentação foram obtidas por entrevistas com mães ou responsáveis durante a Campanha de Multivacinação de 2001. A amamentação foi classificada como exclusiva, predominante (incluindo outros líquidos, exceto leites), complementar (incluindo outros alimentos e/ou leites) e total (soma de exclusivo, predominante e complementar). RESULTADOS: A análise demonstrou que a mediana de amamentação exclusiva foi de 68 dias e a de amamentação total foi de 6,4 meses. No primeiro semestre de vida, 38,1% das crianças estavam em amamentação exclusiva; 23,0% em predominante e 14,9% em complementar. No segundo semestre, 36,5% das crianças recebiam leite materno; no terceiro 26,4% e no quarto 13,9%. Crianças usuárias dos serviços públicos e das unidades locais de saúde apresentaram menor risco de desmame do que as usuárias dos serviços privados e de serviços não locais (p