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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. 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. 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. 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.

Hydrogen sulfide (H2S), originally known as toxic gas, has now attracted attention as one of the gasotransmitters involved in many reactions in the human body. H2S has been assumed to play a role in the pathogenesis of many chronic diseases, of which the exact pathogenesis remains unknown. One of them is inflammatory bowel disease (IBD), a chronic intestinal disease subclassified as Crohn’s disease (CD) and ulcerative colitis (UC). Any change in the amount of H2S seems to be linked to inflammation in this illness. These changes can be brought about by alterations in the microbiota, in the endogenous metabolism of H2S and in the diet. As both too little and too much H2S drive inflammation, a balanced level is needed for intestinal health. The aim of this review is to summarize the available literature published until June 2023 in order to provide an overview of the current knowledge of the connection between H2S and IBD.

Children with obesity have an increased risk of cardiometabolic risk factors, but not all children carry a similar risk. Perinatal factors, i.e., gestational age (GA) and birth weight for GA, may affect the risk for metabolic complications. However, there are conflicting data whether the association between birth size and cardiometabolic risk factors is independent among children with obesity. Moreover, differential effects of GA and birth weight for GA on cardiometabolic risk factors in pediatric obesity are still unexplored. We aimed to investigate the association between birth weight for GA and cardiometabolic risk factors in children and adolescents with overweight or obesity and to assess whether the association is modified by prematurity. We conducted a retrospective study of 2 cohorts, using data from the world's 2 largest registers of pediatric obesity treatment-The Swedish childhood obesity treatment register (BORIS) and The Adiposity Patients Registry (APV) (1991 to 2020). Included were individuals with overweight or obesity between 2 to 18 years of age who had data of birth characteristics and cardiometabolic parameters. Birth data was collected as exposure variable and the first reported cardiometabolic parameters during pediatric obesity treatment as the main outcome. The median (Q1, Q3) age at the outcome measurement was 11.8 (9.4, 14.0) years. The main outcomes were hypertensive blood pressure (BP), impaired fasting glucose, elevated glycated hemoglobin (HbA1c), elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol, and elevated transaminases. With logistic regression, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for each cardiometabolic parameter. All the analyses were adjusted for sex, age, degree of obesity, migratory background, and register source. In total, 42,760 (51.9% females) individuals were included. Small for GA (SGA) was prevalent in 10.4%, appropriate for GA (AGA) in 72.4%, and large for GA (LGA) in 17.2%. Most individuals (92.5%) were born full-term, 7.5% were born preterm. Median (Q1, Q3) body mass index standard deviation score at follow-up was 2.74 (2.40, 3.11) units. Compared with AGA, children born SGA were more likely to have hypertensive BP (OR = 1.20 [95% CI 1.12 to 1.29], p < 0.001), elevated HbA1c (1.33 [1.06 to 1.66], p = 0.03), and elevated transaminases (1.21 [1.10 to 1.33], p < 0.001) as well as low HDL (1.19 [1.09 to 1.31], p < 0.001). On the contrary, individuals born LGA had lower odds for hypertensive BP (0.88 [0.83 to 0.94], p < 0.001), elevated HbA1c (0.81 [0.67 to 0.97], p < 0.001), and elevated transaminases (0.88 [0.81 to 0.94], p < 0.001). Preterm birth altered some of the associations between SGA and outcomes, e.g., by increasing the odds for hypertensive BP and by diminishing the odds for elevated transaminases. Potential selection bias due to occasionally missing data could not be excluded. Among children and adolescents with overweight/obesity, individuals born SGA are more likely to possess cardiometabolic risk factors compared to their counterparts born AGA. Targeted screening and treatment of obesity-related comorbidities should therefore be considered in this high-risk group of individuals.

ContextObesity is associated with hypoadiponectemia, dyslipidemia, and increased risk of cardiovascular disease (CVD). Mechanisms linking these conditions remain to be fully understood. Cholesterol efflux capacity (CEC) is a crucial functional property of high-density lipoprotein (HDL) that strongly predicts CVD incidence.ObjectiveWe investigated whether age, fat distribution, and other obesity-related factors affect CEC in juvenile and adult overweight/obese participants of the STYJOBS/EDECTA cohort (NCT00482924).DesignWe performed an observational study.Main Outcome MeasuresCEC and its association with body measures and related metabolic parameters was assessed in 683 participants (281 juveniles, of whom 227 were overweight/obese; 402 adults, of whom 197 were overweight/obese).ResultsPearson correlation analysis showed that, after Bonferroni correction, CEC was significantly inversely correlated with body mass index (BMI), carotid diameter, waist circumference, waist-to-hip, waist-to-height ratio, oxidized low-density lipoprotein, and uric acid and with the liver markers alanine-aminotransferase and choline esterase. CEC was positively correlated with HDL cholesterol, total cholesterol, apolipoprotein A1, and adiponectin in adults, whereas in juveniles only apolipoprotein A1 showed a significant positive correlation with CEC. Age-stratified linear regression analyses with CEC as the outcome variable identified adiponectin as the most significant predictor of CEC in adults. The results did not change when either BMI or waist-to-hip ratio as a factor of fat distribution was included in the models.ConclusionsHypoadiponectemia is a robust predictor of reduced cholesterol efflux capacity in adults irrespective of BMI and fat distribution. Further investigations are needed to assess whether adiponectin is a causal determinant of CEC.Hypoadiponectemia is a predictor of reduced HDL CEC in adults. Adiponectin production may be a crucial modulator of HDL function with implications for cardiovascular risk.

Consuming a healthy diet in childhood helps to protect against malnutrition and noncommunicable diseases (NCDs). This cross-sectional study described the diets of 132,489 children aged six to nine years from 23 countries participating in round four (2015-2017) of the WHO European Childhood Obesity Surveillance Initiative (COSI). Children's parents or caregivers were asked to complete a questionnaire that contained indicators of energy-balance-related behaviors (including diet). For each country, we calculated the percentage of children who consumed breakfast, fruit, vegetables, sweet snacks or soft drinks \"every day\", \"most days (four to six days per week)\", \"some days (one to three days per week)\", or \"never or less than once a week\". We reported these results stratified by country, sex, and region. On a daily basis, most children (78.5%) consumed breakfast, fewer than half (42.5%) consumed fruit, fewer than a quarter (22.6%) consumed fresh vegetables, and around one in ten consumed sweet snacks or soft drinks (10.3% and 9.4%, respectively); however, there were large between-country differences. This paper highlights an urgent need to create healthier food and drink environments, reinforce health systems to promote healthy diets, and continue to support child nutrition and obesity surveillance.

Background Vedolizumab is safe and effective in adult patients with Crohn’s disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD. Methods Twelve patients (7 female; 7 CD; 5 UC), aged 8–17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor α antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits. Results In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p  = 1,0), while median UC activity scores changed from 70 to 5 points ( p  < 0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups. Conclusion These results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.

BACKGROUND: Polyphenols are chemical compounds of the secondary plant metabolism. High concentrations can be found in various fruits including apples, berries and grapes. Polyphenols are associated with numerous health beneficial effects including a reduced risk for cardiovascular disease or diabetes. The human body cannot synthesize or store polyphenols and relies on continuous replenishment by daily diet. Unfortunately, knowledge on absorption, metabolization and excretion is still limited. The aim of this study was to determine the pharmacokinetic fate of apple polyphenols in young healthy adults. METHODS: Volunteers consumed 500 mL of an unfiltered apple juice. Blood and urine samples were collected within a time period of ten hours and analyzed for their total phenolic content, concentration of selected individual polyphenolic compounds and antioxidant capacity. RESULTS: Large differences in apple polyphenol pharmacokinetics between single subjects were observed. Those could be divided into subgroups according to fast or slow rates of polyphenol metabolism. Some subjects showed no detectable metabolism within the study time frame at all. An increase in the total phenolic content over time did not correlate with an observed, highly elevated antioxidant capacity (AOC) in the blood plasma after apple juice consumption. The determined increase of the AOC was rather a result of a high fructose content of the apple juice. No differences in renal excretion were detected between female and male subjects. However, relative concentrations were slightly higher in male subjects. CONCLUSIONS: Apple derived polyphenols can be readily detected in human blood and urine after juice consumption. The existence of sub-populations with different pharmacokinetics suggests significant variations in the individual metabolism rates of polyphenolic substances with implications on bioavailability and potential health effects within the body. TRIAL REGISTRATION: O2413 (Ethics Commissions of Upper Austria) and 415-EP/73/233-2013 Salzburg (Ethics Commissions of Salzburg).

Introduction: Parents can act as important agents of change and support for healthy childhood growth and development. Studies have found that parents may not be able to accurately perceive their child’s weight status. The purpose of this study was to measure parental perceptions of their child’s weight status and to identify predictors of potential parental misperceptions. Methods: We used data from the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative and 22 countries. Parents were asked to identify their perceptions of their children’s weight status as “underweight,” “normal weight,” “a little overweight,” or “extremely overweight.” We categorized children’s (6–9 years; n = 124,296) body mass index (BMI) as BMI-for-age Z-scores based on the 2007 WHO-recommended growth references. For each country included in the analysis and pooled estimates (country level), we calculated the distribution of children according to the WHO weight status classification, distribution by parental perception of child’s weight status, percentages of accurate, overestimating, or underestimating perceptions, misclassification levels, and predictors of parental misperceptions using a multilevel logistic regression analysis that included only children with overweight (including obesity). Statistical analyses were performed using Stata version 15 1. Results: Overall, 64.1% of parents categorized their child’s weight status accurately relative to the WHO growth charts. However, parents were more likely to underestimate their child’s weight if the child had overweight (82.3%) or obesity (93.8%). Parents were more likely to underestimate their child’s weight if the child was male (adjusted OR [adjOR]: 1.41; 95% confidence intervals [CI]: 1.28–1.55); the parent had a lower educational level (adjOR: 1.41; 95% CI: 1.26–1.57); the father was asked rather than the mother (adjOR: 1.14; 95% CI: 0.98–1.33); and the family lived in a rural area (adjOR: 1.10; 95% CI: 0.99–1.24). Overall, parents’ BMI was not strongly associated with the underestimation of children’s weight status, but there was a stronger association in some countries. Discussion/Conclusion: Our study supplements the current literature on factors that influence parental perceptions of their child’s weight status. Public health interventions aimed at promoting healthy childhood growth and development should consider parents’ knowledge and perceptions, as well as the sociocultural contexts in which children and families live.

The regulatory (neuro)peptide galanin and its three receptors (GAL 1–3 R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GAL 2 R and GAL 3 R contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn’s disease and ulcerative colitis) expressed GAL 2 R and GAL 3 R but not GAL 1 R. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GAL 3 R (GAL 3 R-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GAL 3 R resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GAL 3 R-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GAL 2 R deletion did not influence the course of colitis. In conclusion, granulocyte GAL 2 R and GAL 3 R expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GAL 3 R loss. Consequently, GAL 3 R poses a novel therapeutic target for IBD.