Serum Ferritin Correlates With Liver Fat in Male Adolescents With Obesity.

Non-alcoholic fatty liver disease (NAFLD) contributes essentially to the burden of obesity and can start in childhood. NAFLD can progress to cirrhosis and hepatocellular carcinoma. The early phase of NAFLD is crucial because during this time the disease is fully reversible. Pediatric NAFLD shows unique features of histology and pathophysiology compared to adults. Changes in serum iron parameters are common in adult NAFLD and have been termed dysmetabolic iron overload syndrome characterized by increased serum ferritin levels and normal transferrin saturation; however, the associations of serum ferritin, inflammation, and liver fat content have been incompletely investigated in children. As magnetic resonance imaging (MRI) is an excellent measure for the degree of liver steatosis, we applied this method herein to clarify the interaction between ferritin and fatty liver in male adolescents. For this study, one hundred fifty male pediatric patients with obesity and who are overweight were included. We studied a subgroup of male patients with (n = 44) and without (n = 18) NAFLD in whom we determined liver fat content, visceral adipose tissue, and subcutaneous adipose tissue extent with a 1.5T MRI (Philips NL). All patients underwent a standardized oral glucose tolerance test. We measured uric acid, triglycerides, HDL-, LDL-, total cholesterol, liver transaminases, high sensitive CRP (hsCRP), interleukin-6, HbA1c, and insulin. In univariate analysis, ferritin was associated with MRI liver fat, visceral adipose tissue content, hsCRP, AST, ALT, and GGT, while transferrin and soluble transferrin receptor were not associated with ferritin. Multivariate analysis identified hsCRP and liver fat content as independent predictors of serum ferritin in the pediatric male patients. Our data indicate that serum ferritin in male adolescents with obesity is mainly determined by liver fat content and inflammation but not by body iron status.

Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents.

BACKGROUND: Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored. OBJECTIVES: To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes. METHODS: In 143 subjects (10-20 years), MRI estimates of BAT were assessed as cervical-supraclavicular adipose tissue (sBAT) fat fraction (FF) and T2* from water-fat MRI. FF and T2* of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist-to-height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests. RESULTS: sBAT FF and T2* correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T2* , correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF. CONCLUSIONS: The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT T2* might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T2* quantification.

Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity, and impaired glucose tolerance.

OBJECTIVE: To delineate potential mechanisms for fasting hyperglucagonemia in childhood obesity by studying the associations between fasting plasma glucagon concentrations and plasma lipid parameters and fat compartments. METHODS: Cross-sectional study of children and adolescents with obesity (n = 147) and lean controls (n = 43). Differences in free fatty acids (FFAs), triglycerides, insulin, and fat compartments (quantified by magnetic resonance imaging) across quartiles of fasting plasma glucagon concentration were analyzed. Differences in oral glucose tolerance test (OGTT) glucagon response was tested in high vs low FFAs, triglycerides, and insulin. Human islets of Langerhans were cultured at 5.5 mmol/L glucose and in the absence or presence of a FFA mixture with total FFA concentration of 0.5 mmol/L and glucagon secretion quantified. RESULTS: In children with obesity, the quartile with the highest fasting glucagon had higher insulin (201 ± 174 vs 83 ± 39 pmol/L, P < .01), FFAs (383 ± 52 vs 338 ± 109 µmol/L, P = .02), triglycerides (1.5 ± 0.9 vs 1.0 ± 0.7 mmol/L, P < .01), visceral adipose tissue volume (1.9 ± 0.8 vs 1.2 ± 0.3 dm3 , P < .001), and a higher prevalence of impaired glucose tolerance (IGT; 41% vs 8%, P = .01) than the lowest quartile. During OGTT, children with obesity and high insulin had a worse suppression of glucagon during the first 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in islets treated with FFAs than in those not treated with FFAs. CONCLUSIONS: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, high plasma FFAs, high plasma triglycerides, visceral adiposity, and IGT. The glucagonotropic effect of FFAs on isolated human islets provides a potential mechanism linking high fasting plasma FFAs and glucagon levels.

High DPP-4 Concentrations in Adolescents Are Associated With Low Intact GLP-1.

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.

[Gender differences of psychological, nutritional, and physical fitness variables influencing obesity/overweight in Austrian children and adolescents]. / Geschlechtsunterschiede bei psychologischen, ernährungs- und sportwissenschaftlichen Einflussfaktoren auf Adipositas/Übergewicht bei Kindern und Jugendlichen in Österreich.

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.

Pain in the Early Phase of Pediatric Pancreatitis (PINEAPPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial.

BACKGROUND: There are unexpectedly large differences between the incidences of acute pancreatitis (AP) as indicated by different hospitals. Retrospective studies suggest that the reason behind this is the large differences that exist between the local managements of abdominal pain at emergency units. Unfortunately, no evidence-based medicine (EBM) guidelines are available to give proper instruction concerning the necessity of serum pancreatic enzyme measurement during abdominal pain. SUMMARY: Pain in Early Phase of Pediatric Pancreatitis (PINEAPPLE) is an observational, multinational observational clinical trial to explore the route from the first sign of abdominal pain to the diagnosis of pancreatitis (PINEAPPLE trial). The PINEAPPLE-R subtrial is a retrospective review on the records of children (patients under 18) appearing at emergency units - a review of their clinical symptoms, results of imaging examinations and laboratory parameters. The PINEAPPLE-P subtrial is a prospective trial designed to develop a fast and simple EBM guideline that helps to evaluate (in a reliable and cost-efficient way) the necessity of pancreatic enzyme test and abdominal ultrasonography (or even computed tomography) when a child has abdominal pain. The trial has been registered at the ISRCTN registry and has received the relevant ethical approval. KEY MESSAGE: The PINEAPPLE trial will help to recognize AP in children in a highly efficient manner.

Analysis of Pediatric Pancreatitis (APPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial.

BACKGROUND: Single-centered studies show increased number of acute pancreatitis (AP) in children. Here, the Pediatric Section of the Hungarian Pancreatic Study Group introduces an international observational clinical trial (APPLE) to collect a critical mass of clinical data and biomedical research samples in a uniform prospective manner. SUMMARY: The APPLE-R is for patients under 18 years of age with a history of pancreatitis. The study primarily provides information on possible genetic variants behind the disease and their impact on the prognosis. The APPLE-P is for patients under 18 years of age with a diagnosis of AP. Children with AP diagnosed based on the fulfillment of '2 out of 3' of the Atlanta criteria will be selected. This subtrial requests detailed information from the medical history, etiology, complains and symptoms, physical examinations, laboratory parameters, imaging, immediate therapy at admission and complications of the disease. The APPLE trial has been registered at the ISRCTN registry and has received the relevant ethical approval. The study is open for all pediatric centers throughout the world. KEY MESSAGE: This is the first worldwide study tracking earlier (APPLE-R) and ongoing episodes (APPLE-P) of pancreatitis.

Tricellulin expression in normal and neoplastic human pancreas.

AIMS: Tricellulin is a member of the family of tight junction proteins, which are found concentrated mainly at tricellular contacts. Altered expression of several tight junction components has been observed during carcinogenesis. In the present study, we have analysed the expression of tricellulin in normal human pancreas, and in primary exocrine and endocrine pancreatic tumours. METHODS AND RESULTS: A total of 96 cases were studied: 20 normal pancreas, 58 pancreatic ductal adenocarcinomas, 15 pancreatic endocrine neoplasms, and three acinar cell carcinomas. Immunohistochemistry (analysed by digital morphometry), immunofluorescence, western blot analysis and reverse transcription polymerase chain reaction were performed. Tricellulin was localized apically in normal ducts and acini as intensive, spotty immunopositivity at tricellular contacts, whereas weaker signals were observed at the junction between two cells. Islets of Langerhans were negative. Well-differentiated ductal adenocarcinomas significantly overexpressed tricellulin as compared with poorly differentiated adenocarcinomas. Acinar cell carcinomas expressed tricellulin in tumour cells. All endocrine tumours were tricellulin-negative. CONCLUSIONS: This is the first report to describe the tricellulin expression profile in normal and neoplastic human pancreas. Both normal and neoplastic pancreatic exocrine tissues expressed tricellulin, whereas no expression was seen in normal or neoplastic endocrine cells. Tricellulin expression in pancreatic ductal adenocarcinomas showed a significant negative correlation with the degree of differentiation.