RESUMEN
Context: Dipeptidyl peptidase 4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1), and increased DPP4 levels are associated with obesity and visceral adiposity in adults. Objective: Investigating DPP-4 levels in adolescents and their association with (1) circulating intact GLP-1 levels and glucose tolerance; (2) body mass index (BMI); and (3) visceral, subcutaneous, and liver fat compartments. Design: Cross-sectional study, July 2012 to April 2015. Setting: Pediatric obesity clinic, Uppsala University Hospital. Patients and Participants: Children and adolescents with obesity (n = 59) and lean controls (n = 21) aged 8 to 18 years. Main Outcome Measures: BMI SD score, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and oral glucose tolerance test (OGTT) concentrations of glucose, and visceral adipose tissue (VAT) and subcutaneous adipose tissue volumes and liver fat fraction. Results: Plasma DPP-4 levels decreased with age in both obese (41 ng/mL per year) and lean subjects (48 ng/mL per year). Plasma DPP-4 levels were higher in males in both the obesity and lean groups. With adjustments for age and sex, plasma DPP-4 level was negatively associated with intact GLP-1 at fasting (ß = -12.3; 95% CI: -22.9, -1.8) and during OGTT (ß = -12.1; 95% CI: -22.5, -1.7). No associations were found between DPP-4 and plasma glucose levels measured at fasting or after a 2-hour OGTT. Plasma DPP-4 level was 19% higher in obese subjects. Among adipose tissue compartments, the strongest association was with VAT (ß = 0.05; 95% CI: -0.02, 0.12). Conclusions: In adolescents, high plasma DPP-4 concentrations were associated with low proportions of intact GLP-1, high BMI, young age, and male sex. The observed associations are compatible with increased metabolism of GLP-1 in childhood obesity.
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Dipeptidil Peptidasa 4/sangre , Péptido 1 Similar al Glucagón/sangre , Obesidad Infantil/sangre , Adiposidad , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Grasa Intraabdominal/patología , Masculino , Obesidad Infantil/patología , Grasa Subcutánea/patologíaRESUMEN
OBJECTIVE: Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further. METHODS: We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging. RESULTS: The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS. CONCLUSIONS: In adolescents with obesity, PFF is elevated and associated to MetS, fasting glucose, and visceral adipose tissue but not to beta-cell function, glucose tolerance, or BMI-SDS. This study demonstrates that conclusions regarding PFF and its associations depend on the body mass features of the cohort.
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Tejido Adiposo/metabolismo , Células Secretoras de Insulina/metabolismo , Grasa Intraabdominal/metabolismo , Síndrome Metabólico/metabolismo , Páncreas/metabolismo , Obesidad Infantil/metabolismo , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Obesidad/metabolismoRESUMEN
BACKGROUND: The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS: Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ(2) test. RESULTS: The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C(0.185)/(TG(0.2) × BMI(1.338)), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m(2)). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg(-1) · min(-1) (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment-insulin resistance) when calculated with M-values. CONCLUSIONS: The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.
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HDL-Colesterol/sangre , Diabetes Mellitus/sangre , Insulina/sangre , Obesidad/sangre , Triglicéridos/sangre , Adolescente , Adulto , Estudios de Cohortes , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Eating behavior and physical activity behavior are under the control of certain cognitive patterns. 6600 adults and 4400 children/adolescents (8-18 years) were tested with the Obesity Diagnostics and Evaluation System (AD-EVA). Potentially significant gender differences will be detailed for the entire juvenile cohort, the subgroup of obese children/adolescents as compared to the adult cohort in this article.Among all the subscales tested, obese girls primarily showed significantly higher values of (preclinical) eating disorders than boys. These data are relevant for both prevention and health promotion.No significant differences were found in regard to sports motivation. This warrants facilitation of physical activity for both genders. Further, a male predilection for "Snacks" and "High-fat food" that could be found in the total representative study group, could not be verified in the subgroup of obese girls and boys, thus suggesting a similarily unhealthy eating behavior in both genders of juvenility.
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Ejercicio Físico/psicología , Conducta Alimentaria/psicología , Sobrepeso/epidemiología , Sobrepeso/psicología , Obesidad Infantil/epidemiología , Obesidad Infantil/psicología , Aptitud Física , Caracteres Sexuales , Adolescente , Austria , Niño , Femenino , Conductas Relacionadas con la Salud , Promoción de la Salud , Humanos , Masculino , Motivación , Encuestas Nutricionales , Sobrepeso/prevención & control , Obesidad Infantil/prevención & control , Factores de RiesgoRESUMEN
OBJECTIVE: Despite alarming prevalence rates, surprisingly little is known about neural mechanisms underlying eating behavior in juveniles with obesity. To simulate reactivity to modern food environments, event-related potentials (ERP) to appetizing food images (relative to control images) were recorded in adolescents with obesity and healthy adolescents. METHODS: Thirty-four adolescents with obesity (patients) and 24 matched healthy control adolescents watched and rated standardized food and object images during ERP recording. Personality (impulsivity) and eating styles (trait craving and dietary restraint) were assessed as potential moderators. RESULTS: Food relative to object images triggered larger early (P100) and late (P300) ERPs. More impulsive individuals had considerably larger food-specific P100 amplitudes in both groups. Controls with higher restraint scores showed reduced food-specific P300 amplitudes and subjective palatability ratings whereas patients with higher restraint scores showed increased P300 and palatability ratings. CONCLUSIONS: This first ERP study in adolescents with obesity and controls revealed impulsivity as a general risk factor in the current obesogenic environment by increasing food-cue salience. Dietary restraint showed paradoxical effects in patients, making them more vulnerable to visual food-cues. Salutogenic therapeutic approaches that deemphasize strict dietary restraint and foster healthy food choice might reduce such paradoxical effects.
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Restricción Calórica/psicología , Dieta/psicología , Potenciales Evocados/fisiología , Conducta Impulsiva/fisiología , Red Nerviosa/fisiología , Obesidad Infantil/dietoterapia , Obesidad Infantil/psicología , Adolescente , Salud del Adolescente , Estudios de Casos y Controles , Niño , Señales (Psicología) , Conducta Alimentaria/fisiología , Femenino , Alimentos , Humanos , MasculinoRESUMEN
BACKGROUND: Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians. METHODOLOGY AND PRINCIPAL FINDINGS: Using SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2-2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects. CONCLUSIONS AND SIGNIFICANCE: By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor.
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ADN Mitocondrial/genética , Haplotipos/genética , Mitocondrias/genética , Obesidad/genética , Población Blanca/genética , Adolescente , Austria , Niño , Etnicidad/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
Obesity is a rapidly growing health problem and is paralleled by a multitude of comorbidities, including nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common chronic liver disease in both adults and children. The current understanding of NAFLD is still fragmentary. While simple steatosis is characterized by the interplay between excessive free fatty acid accumulation and hepatic insulin resistance, the progression to NASH has been related to oxidative stress and a proinflammatory state with dysbalanced adipokine, cytokine levels, and endotoxin-mediated immune response. In addition, oxidative stress has been suggested to play a central role for the sequelae leading to NASH. Trace elements are critical in regulatory, immunologic, and antioxidant functions resulting in protection against inflammation and peroxidation and consequently against the known comorbidities of obesity. Disruptions of the metal detoxification processes located in the liver are plausibly related to NAFLD development via oxidative stress. Perturbations of iron and copper (Cu) homeostasis have been shown to contribute to the pathogenesis of NAFLD. This review presents current data from pediatric studies. In addition, data from adult studies are summarized where clinical relevance may be extrapolated to pediatric obesity and NAFLD.
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Cobre/metabolismo , Hierro/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad Infantil/metabolismo , Obesidad Infantil/patología , Animales , Humanos , Inflamación/metabolismo , Inflamación/patología , Estrés Oxidativo/fisiologíaRESUMEN
OBJECTIVE: Obesity-related immune mediated systemic inflammation was associated with the development of the metabolic syndrome by induction of the tryptophan (TRP)-kynurenine (KYN) pathway. The study aimed to assess whether this holds true across the lifespan from juvenility to adulthood. DESIGN AND METHODS: Five hundred twenty-seven participants aged between 10 and 65 years were analyzed. Standard anthropometric measures, carotid ultrasound, and laboratory analysis including interleukin-6, ultra-sensitive C-reactive protein, lipids, glucose metabolism, neopterin, TRP, KYN levels, and the KYN/TRP ratio were performed. RESULTS: Overweight/obese (ow/ob) adults had significantly increased KYN serum levels and a significantly increased KYN/TRP ratio. In sharp contrast, ow/ob juvenile males aged ≤18 years showed decreased, females similar KYN and KYN/TRP ratio in comparison to their control counterparts. Also, adult ow/ob subjects with metabolic syndrome showed markedly increased KYN/TRP ratios contrary to decreased KYN/TRP ratios in ow/ob juveniles. Abdominal fat content, characterized by age normalized waist circumference, and not body mass index, had the strongest effect for an increase of the KYN/TRP ratio in adults. CONCLUSIONS: TRP metabolism and obesity-related immune mediated inflammation differs markedly between juveniles and adults. While childhood obesity seems to be dominated by a Th2-driven activation, an accelerated production of Th1-type cytokines may pave the way for later atherosclerotic endpoints.
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Quinurenina/sangre , Síndrome Metabólico/sangre , Obesidad/sangre , Triptófano/sangre , Adolescente , Adulto , Factores de Edad , Anciano , Proteína C-Reactiva/metabolismo , Niño , Femenino , Humanos , Interleucina-6/sangre , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Neopterin/metabolismo , Obesidad/complicaciones , Obesidad/fisiopatología , Estudios Observacionales como Asunto , Adulto JovenRESUMEN
BACKGROUND/AIMS: To determine i) whether obesity in childhood can be related to malalignment of the distal extremities, ii) the proportion of genu valgum malalignment and abduction setting, and iii) the respective deviation dominance in children who are morbidly obese. METHODS: 31 morbidly obese Caucasian children (16 males) recruited for the STYJOBS Study (ClinicalTrials.gov Identifier NCT00482924) with a mean age of 13.9 ± 0.5 years, a mean height of 162.3 ± 2.7 cm, a mean weight of 90.62 ± 5.0 kg, and a mean BMI of 33.8 ± 1.2 kg/m(2) were clinically examined using the Mikulicz line in order to assess load distribution on the knee joint. 21 participants received a whole-leg X-ray because of a clinically estimated malalignment. RESULTS: 8/31 participants examined were diagnosed with genu valgum, 1/31 with genu varum, and 22/31 did not have any malalignment of the femur or tibia. The majority of genu valgum presentation was due to femoral deviation. Of those without malalignment, 4/22 participants had an abduction setting, while 2/22 showed an adduction of the leg. CONCLUSION: Genu valgum as a predominant malalignment of the distal extremities is frequent in youth with morbid obesity. Timely guided correction of angular deformity of the knee seems pivotal in order to avoid osteotomy or osteoarthritis later in life.
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Desviación Ósea/diagnóstico por imagen , Huesos/diagnóstico por imagen , Genu Valgum/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Pierna/diagnóstico por imagen , Obesidad Mórbida/complicaciones , Adolescente , Índice de Masa Corporal , Peso Corporal , Desviación Ósea/diagnóstico , Desviación Ósea/epidemiología , Desviación Ósea/etiología , Huesos/cirugía , Femenino , Fémur/diagnóstico por imagen , Genu Valgum/diagnóstico , Genu Valgum/epidemiología , Genu Valgum/etiología , Humanos , Pierna/cirugía , Masculino , Obesidad Mórbida/diagnóstico por imagen , Osteotomía , Prevalencia , Radiografía , Tibia/diagnóstico por imagen , Soporte de Peso , Población BlancaRESUMEN
OBJECTIVES: We set out to investigate the major obstacles in achieving a sensitive and supportive communication between parents and clinicians in ethical dilemma situations. We focused on discussions in emergency situations by means of values clarification. METHODS: The study population (n=141) covers four samples of clinical staff (n(1)=72) from different specialties and parents of preterm and term infants (n(2)=69). Because of the vulnerability of parents and the virulence of the topic, the descriptive qualitative case study comprises standardized questionnaires and half-standardized interviews. Data were analyzed graphically and statistically, comparing parents and professionals for the justification of acting using values clarification in this context. RESULTS: Our study indicated that the use of a critically reconsidered and less personalized language has to be a major goal in the care of preterm infants at the edge of viability. Furthermore we found that acting ethically means making decisions individually by using open-context terms sensitively in consideration of diverging action-guiding principles. CONCLUSIONS: Decisions in medicine concern different people - experts as well as patients and their representatives. The present study is an attempt to establish more awareness for improved communication, which is a part of professionalism, as well as coping strategies for all involved.