Arginine-induced glucagon secretion and glucagon-induced enhancement of amino acid catabolism are not influenced by ambient glucose levels in mice.

Amino acids stimulate the secretion of glucagon, and glucagon receptor signaling regulates amino acid catabolism via ureagenesis, together constituting the liver-α cell axis. Impairment of the liver-α cell axis is observed in metabolic diseases such as diabetes. It is, however, unknown whether glucose affects the liver-α cell axis. We investigated the role of glucose on the liver-α cell axis in vivo and ex vivo. The isolated perfused mouse pancreas was used to evaluate the direct effect of low (3.5 mmol/L) and high (15 mmol/L) glucose levels on amino acid (10 mmol/L arginine)-induced glucagon secretion. High glucose levels alone lowered glucagon secretion, but the amino acid-induced glucagon responses were similar in high and low glucose conditions (P = 0.38). The direct effect of glucose on glucagon and amino acid-induced ureagenesis was assessed using isolated perfused mouse livers stimulated with a mixture of amino acids (VaminR, 10 mmol/L) and glucagon (10 nmol/L) during high and low glucose conditions. Urea production increased robustly but was independent of glucose levels (P = 0.95). To investigate the whole body effects of glucose on the liver-α cell axis, four groups of mice received intraperitoneal injections of glucose-Vamin (2 g/kg, + 3.5 µmol/g, respectively, G/V), saline-Vamin (S/V), glucose-saline (G/S), or saline-saline (S/S). Blood glucose did not differ significantly between G/S and G/V groups. Levels of glucagon and amino acids were similar in the G/V and S/V groups (P = 0.28). Amino acids may overrule the inhibitory effect of glucose on glucagon secretion and the liver-α cell axis may operate independently of glucose in mice.NEW & NOTEWORTHY Glucagon is an essential regulator of our metabolism. Recent evidence suggests that the physiological actions of glucagon reside in amino acid catabolism in the so-called liver-α cell axis, in which amino acids stimulate glucagon secretion and glucagon enhances hepatic amino acid catabolism. Here, it is demonstrated that this feedback system is independent of glycemia possibly explaining why hyperglycemia in diabetes may not suppress α cell secretion.

Childhood obesity prevention: what can be achieved?

PURPOSE OF REVIEW: Childhood obesity is a pandemic generating an enormous individual and socioeconomic burden worldwide. This narrative review summarizes recent evidence on successful and recommended prevention strategies according to age groups and different levels of interventions. RECENT FINDINGS: Effective prevention of childhood obesity is feasible and most successful early in life up to preschool age, and it should include a multicomponent approach, integrating individuals, family and society. Trials that improve nutrition and/or enhance physical activity are the cornerstones of childhood obesity prevention on an individual level. However, their efficacy is determined by the combination of interventions for the target age group. Further, improving family support and sleep, as well as reducing screen time, lead to favourable results. Many research gaps remain, including a lack of effective interventions for high-risk groups. SUMMARY: As a multifactorial condition, childhood obesity requires a multicomponent approach. Interventions should be developmental stage-specific and adjusted to the setting. Current research gaps need to be targeted by future trials, with a special focus on the benefit of the most vulnerable groups. From a systems response perspective, a paradigm shift from interventions focusing on the individual to approaches that target society as a whole is warranted.

Association between alanine aminotransferase as surrogate of fatty liver disease and physical activity and sedentary time in adolescents with obesity.

To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p < 0.05), higher AST/ALT (p < 0.01)) vs SED + and in MVPA + (lower ALT (p < 0.05), higher AST/ALT (p < 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p < 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time. CONCLUSION: Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible. WHAT IS KNOWN: • MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population. WHAT IS NEW: • Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.

Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women.

Recent human and animal studies have found associations between gut microbiota composition and serum levels of sex hormones, indicating that they could be an important factor in shaping the microbiota. However, little is known about the effect of regular hormonal fluctuations over the menstrual cycle or CHC-related changes of hormone levels on gut microbiota structure, diversity and dynamics. The aim of this study was to investigate the effect of CHCs on human gut microbiota composition. The effect of CHC pill intake on gut microbiota composition was studied in a group of seven healthy pre-menopausal women using the CHC pill, compared to the control group of nine age-matched healthy women that have not used hormonal contraceptives in the 6 months prior to the start of the study. By analysing the gut microbiota composition in both groups during one menstrual cycle, we found that CHC usage is associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. These results call for further investigation of the mechanisms underlying hormonal and hormonal contraceptive-related changes of the gut microbiota and the potential implications of these changes for women's health.

The Fatty Liver Index (FLI) Relates to Diabetes-Specific Parameters and an Adverse Lipid Profile in a Cohort of Nondiabetic, Dyslipidemic Patients.

BACKGROUND: Patients with hyperlipidemia are at high risk for developing a fatty liver. The fatty liver index (FLI) is a noninvasive and well-established method for the estimation of a fatty liver. However, little is known about the metabolic characterization of nondiabetic treated patients with hyperlipidemia who have different risk levels for a fatty liver. METHODS: In this study, 74 nondiabetic patients with hyperlipidemia were divided into 3 groups according to their fatty liver index. A comparison of metabolic characteristics was done. These characteristics included intima media thickness (IMT) and nutritional habits, which were further divided into FLI subgroups with low, intermediate, and high risk for a fatty liver. RESULTS: Patients with hyperlipidemia, with a high risk for a fatty liver (FLI ≥ 60), had subclinical elevations in parameters of carbohydrate metabolism (insulin, fasting plasma glucose, C-peptide) including a higher insulin resistance (quantitative insulin sensitivity check index, QUICKI) compared to lower FLI groups. These patients also presented a higher risk for a metabolic syndrome (p = 0.018), as well as an adverse lipid profile (e.g., high-density lipoprotein [HDL] cholesterol, triglycerides [TG]-HDL ratio). FLI group 3 was characterized by significantly lower levels of omega-3 fatty acids (p = 0.048). CONCLUSION: The fatty liver index relates to diabetes-specific parameters and an adverse lipid profile and is an appropriate index for risk evaluation of metabolic syndrome.

Rise in fasting and dynamic glucagon levels in children and adolescents with obesity is moderate in subjects with impaired fasting glucose but accentuated in subjects with impaired glucose tolerance or type 2 diabetes.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 ± 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

The Role of Macronutrients in the Pathogenesis, Prevention and Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) in the Paediatric Population-A Review.

Paediatric non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Obesity is the main risk factor. Nutrition and lifestyle are the key elements in preventing and treating NAFLD in the absence of approved drug therapy. Whilst recommendations and studies on macronutrients (carbohydrates, fat and protein) in adult NAFLD exist, the discussion of this topic in paediatric NAFLD remains contradictory. The purpose of this review is to provide state-of-the-art knowledge on the role of macronutrients in paediatric NAFLD regarding quality and quantity. PubMed was searched and original studies and review articles were included in this review. Fructose, sucrose, saturated fatty acids, trans-fatty acids and ω-6-fatty-acids are strongly associated with paediatric NAFLD. High consumption of fibre, diets with a low glycaemic index, mono-unsaturated-fatty-acids and ω-3-fatty-acids reduce the risk of childhood-onset NAFLD. Data regarding the role of dietary protein in NAFLD are contradictory. No single diet is superior in treating paediatric NAFLD, although the composition of macronutrients in the Mediterranean Diet appears beneficial. Moreover, the optimal proportions of total macronutrients in the diet of paediatric NAFLD patients are unknown. Maintaining a eucaloric diet and avoiding saturated fatty acids, simple sugars (mainly fructose) and a high-caloric Western Diet are supported by literature.

Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease.

Background: Attenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity. Materials and Methods: Ninety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5. Results: SPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%). Conclusion: SPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.

Sedentary time has a stronger impact on metabolic health than moderate to vigorous physical activity in adolescents with obesity: a cross-sectional analysis of the Beta-JUDO study.

BACKGROUND: Relationships between movement-related behaviours and metabolic health remain underexplored in adolescents with obesity. OBJECTIVES: To compare profiles of sedentary time (more sedentary, SED+ vs. less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA+ vs. less active, MVPA-) and combinations of behaviours (SED-/MVPA+, SED-/MVPA-, SED+/MVPA+, SED+/MVPA-) in regard to metabolic health. METHODS: One hundred and thirty-four subjects (mean age 13.4 ± 2.2 yrs, mean body mass index [BMI] 98.9 ± 0.7 percentile, 48.5% females) underwent 24 h/7 day accelerometry, anthropometric, body composition, blood pressure (BP), lipid profile and insulin resistance (IR) assessments. RESULTS: Metabolic health was better in SED- [lower fat mass (FM) percentage (p < 0.05), blood pressure (BP) (p < 0.05), homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.001) and metabolic syndrome risk score (MetScore) (p < 0.001), higher high-density lipoprotein-cholesterol (HDL-c) (p = 0.001)] vs. SED+ group and in MVPA+ [lower triglyceridemia (TG), (p < 0.05), HOMA-IR (p < 0.01) and MetScore (p < 0.001), higher HDL-c (p < 0.01)] vs. MVPA- group after adjustment with age, gender, maturation and BMI. SED-/MVPA+ group had the best metabolic health. While sedentary (p < 0.001) but also MVPA times (p < 0.001) were lower in SED-/MVPA- vs. SED+/MVPA+, SED-/MVPA- had lower FM percentage (p < 0.05), HOMA-IR (p < 0.01) and MetScore (p < 0.05) and higher HDL-c (p < 0.05), independently of BMI. Sedentary time was positively correlated with HOMA-IR and Metscore and negatively correlated with HDL-c after adjustment with MVPA (p < 0.05). MVPA was negatively correlated with HOMA-IR, BP and MetScore and positively correlated with HDL-c after adjustment with sedentary time (p < 0.05). CONCLUSION: Lower sedentary time is associated with a better metabolic health independently of MVPA and might be a first step in the management of pediatric obesity when increasing MVPA is not possible.

The relationship between glucose and the liver-alpha cell axis - A systematic review.

Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects.

Determinants of hyperglucagonemia in pediatric non-alcoholic fatty liver disease.

Objective: Over the years, non-alcoholic fatty liver (NAFLD) disease has progressed to become the most frequent chronic liver disease in children and adolescents. The full pathology is not yet known, but disease progression leads to cirrhosis and hepatocellular carcinoma. Risk factors included hypercaloric diet, obesity, insulin resistance and genetics. Hyperglucagonemia appears to be a pathophysiological consequence of hepatic steatosis, thus, the hypothesis of the study is that hepatic fat accumulation leads to increased insulin resistance and impaired glucagon metabolism leading to hyperglucagonemia in pediatric NAFLD. Methods: 132 children and adolescents between 10 and 18 years, with varying degrees of obesity, were included in the study. Using Magnetic Resonance Imaging (MRI) average liver fat was determined, and patients were stratified as NAFLD (>5% liver fat content) and non-NAFLD (<5%). All patients underwent a standardized oral glucose tolerance test (OGTT). Additionally, anthropometric parameters (height, weight, BMI, waist circumference, hip circumference) such as lab data including lipid profile (triglycerides, HDL, LDL), liver function parameters (ALT, AST), uric acid, glucose metabolism (fasting insulin and glucagon, HbA1c, glucose 120 min) and indices evaluating insulin resistance (HIRI, SPISE, HOMA-IR, WBISI) were measured. Results: Children and adolescents with NAFLD had significantly higher fasting glucagon values compared to the non-NAFLD cohort (p=0.0079). In the NAFLD cohort univariate analysis of fasting glucagon was associated with BMI-SDS (p<0.01), visceral adipose tissue volume (VAT) (p<0.001), average liver fat content (p<0.001), fasting insulin concentration (p<0.001), triglycerides (p<0.001) and HDL (p=0.034). This correlation equally applied to all insulin indices HOMA-IR, WBISI, HIRI (all p<0.001) and SPISE (p<0.002). Multivariate analysis (R² adjusted 0.509) for the same subgroup identified HIRI (p=0.003) and VAT volume (p=0.017) as the best predictors for hyperglucagonemia. Average liver fat content is predictive in pediatric overweight and obesity but not NAFLD. Conclusions: Children and adolescents with NAFLD have significantly higher fasting plasma glucagon values, which were best predicted by hepatic insulin resistance and visceral adipose tissue, but not average liver fat content.

The Role of Protein and Fat Intake on Insulin Therapy in Glycaemic Control of Paediatric Type 1 Diabetes: A Systematic Review and Research Gaps.

Carbohydrate counting (CHC) is the established form of calculating bolus insulin for meals in children with type 1 diabetes (T1DM). With the widespread use of continuous glucose monitoring (CGM) observation time has become gapless. Recently, the impact of fat, protein and not only carbohydrates on prolonged postprandial hyperglycaemia have become more evident to patients and health-care professionals alike. However, there is no unified recommendation on how to calculate and best administer additional bolus insulin for these two macronutrients. The aim of this review is to investigate: the scientific evidence of how dietary fat and protein influence postprandial glucose levels; current recommendations on the adjustment of bolus insulin; and algorithms for insulin application in children with T1DM. A PubMed search for all articles addressing the role of fat and protein in paediatric (sub-)populations (<18 years old) and a mixed age population (paediatric and adult) with T1DM published in the last 10 years was performed. Conclusion: Only a small number of studies with a very low number of participants and high degree of heterogeneity was identified. While all studies concluded that additional bolus insulin for (high) fat and (high) protein is necessary, no consensus on when dietary fat and/or protein should be taken into calculation and no unified algorithm for insulin therapy in this context exists. A prolonged postprandial observation time is necessary to improve individual metabolic control. Further studies focusing on a stratified paediatric population to create a safe and effective algorithm, taking fat and protein into account, are necessary.

Association between Metabolic Syndrome Diagnosis and the Physical Activity-Sedentary Profile of Adolescents with Obesity: A Complementary Analysis of the Beta-JUDO Study.

Metabolic syndrome (MetS) is highly prevalent in children and adolescents with obesity and places them at an increased risk of cardiovascular-related diseases. However, the associations between objectively measured movement-related behaviors and MetS diagnosis remain unexplored in youths with obesity. The aim was to compare profiles of sedentary (SED) time (more sedentary, SED+ vs. less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA+ vs. less active, MVPA-) and combinations of behaviors (SED-/MVPA+, SED-/MVPA-, SED+/MVPA+, SED+/MVPA-) regarding the MetS diagnosis. One hundred and thirty-four adolescents with obesity (13.4 ± 2.2 years) underwent 24 h/7 day accelerometry, waist circumference (WC), blood pressure (BP), high-density lipoprotein-cholesterol (HDL-c), triglycerides (TG) and insulin-resistance (IR) assessments. Cumulative cardiometabolic risk was assessed by using (i) MetS status (usual dichotomic definition) and (ii) cardiometabolic risk z-score (MetScore, mean of standardized WC, BP, IR, TG and inverted HDL-c). SED- vs. SED+ and MVPA+ vs. MVPA- had lower MetS (p < 0.01 and p < 0.001) and MetScore (p < 0.001). SED-/MVPA+ had the lowest risk. While SED and MVPA times were lower in SED-/MVPA- vs. SED+/MVPA+ (p < 0.001), MetScore was lower in SED-/MVPA- independently of body mass index (BMI) (p < 0.05). MVPA, but not SED, time was independently associated with MetS diagnosis (p < 0.05). Both MVPA (p < 0.01) and SED times (p < 0.05) were associated with MetScore independently of each other. A higher MVPA and lower SED time are associated with lower cumulative cardiometabolic risk.

Cardiometabolic efficacy of multidisciplinary weight loss interventions is not altered in adolescents with obesity initially diagnosed or with a persistent metabolic syndrome.

The efficacy of weight loss interventions might be affected by the metabolic profile of adolescents with obesity. In this study, we hypothesized that the initial diagnosis of the MS, or its persistence after an intervention, will not reduce the efficacy of a 16-week multidisciplinary weight loss program. Ninety two adolescents (12-15 years; 62 girls) with obesity completed baseline anthropometric and body composition evaluation (DXA). Lipid profile, insulinemia, glycaemia and blood pressure were measured and metabolic syndrome (MS) diagnosed. The adolescents then followed a 4-month inpatient multidisciplinary weight-management program. All measurements were performed before (T0) and after 4 months of intervention (T1). Body weight, body mass index (BMI) and percentage of fat mass (%FM) decreased significantly between T0 and T1 (P< .001), with no difference in fat-free mass (kg). All metabolic variables (except blood pressure) were improved. 47.6% of the whole sample presented with MS at baseline against 35.7% at T1. Body weight (P = 0.006), BMI (P = 0.0261), %FM (P = 0.0211), hip circumference (= 0.0131), BMI percentile (P = 0.0319), and diastolic blood pressure (P = 0.0365) showed a time x group interaction and their deltas (variations between T0 and T1) were significantly different between adolescents with and without MS at baseline. There was no significant difference between adolescents with persistent and nonpersistent MS except for ΔBMI percentile that deceased significantly more in the nonpersistent group (P = 0.0115). According to our results, the efficacy of weight loss interventions is not reduced in adolescents initially diagnosed with MS or different between those who present a persistent or nonpersistent MS after the intervention.

Socioeconomic inequalities in overweight and obesity among 6- to 9-year-old children in 24 countries from the World Health Organization European region.

Childhood overweight and obesity have significant short- and long-term negative impacts on children's health and well-being. These challenges are unequally distributed according to socioeconomic status (SES); however, previous studies have often lacked standardized and objectively measured data across national contexts to assess these differences. This study provides a cross-sectional picture of the association between SES and childhood overweight and obesity, based on data from 123,487 children aged 6-9 years in 24 countries in the World Health Organization (WHO) European region. Overall, associations were found between overweight/obesity and the three SES indicators used (parental education, parental employment status, and family-perceived wealth). Our results showed an inverse relationship between the prevalence of childhood overweight/obesity and parental education in high-income countries, whereas the opposite relationship was observed in most of the middle-income countries. The same applied to family-perceived wealth, although parental employment status appeared to be less associated with overweight and obesity or not associated at all. This paper highlights the need for close attention to context when designing interventions, as the association between SES and childhood overweight and obesity varies by country economic development. Population-based interventions have an important role to play, but policies that target specific SES groups are also needed to address inequalities.

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.

Pericardial Fat Relates to Disturbances of Glucose Metabolism in Women with the Polycystic Ovary Syndrome, but Not in Healthy Control Subjects.

OBJECTIVE: The objective of the present study is to investigate the relationship of cardiac fat depots with disturbances of the carbohydrate metabolism in women with PCOS. METHODS: An oral glucose tolerance test (OGTT) was realized, and metabolic parameters were collected in 48 women with PCOS and in 20 controls. Intramyocardial fat (MYCL) and pericardial fat (PERI) were measured using 1H-magnetic resonance spectroscopy and imaging. RESULTS: Only in PCOS women, PERI was positively and independently related to parameters of glucose metabolism (HbA1c: p = 0.001, fasting plasma glucose: p < 0.001, stimulated glucose at 30 and 60 minutes in the OGTT). Thus, the disposition index, insulin sensitivity, and adiponectin also declined with the increase of PERI in women with PCOS; however, these results were not independent of BMI and age. In addition, PERI was positively related to atherogenic lipid profiles, BMI, waist circumference, CRP, and liver fat in women with PCOS. A negative relation of PERI with triglycerides and a positive relation with BMI and waist circumference could be observed in the controls. No relationship of MYCL with diabetes-specific parameters could be found in the study population. CONCLUSION: PERI is related to metabolic disturbances in women with PCOS, but not in metabolically healthy lean subjects. This clinical trial was registered at ClinicalTrials.gov and has the registration number NCT03204461.