Katharina Paulmichl

Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome.

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.

Dietary restraint and impulsivity modulate neural responses to food in adolescents with obesity and healthy adolescents.

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.

The Potential Role of Iron and Copper in Pediatric Obesity and Nonalcoholic Fatty Liver Disease

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.

Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity

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.

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults

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.

Timely Diagnosis of Malalignment of the Distal Extremities Is Crucial in Morbidly Obese Juveniles

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/m2 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.

Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)

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.

Geschlechtsunterschiede bei psychologischen, ernährungs- und sportwissenschaftlichen Einflussfaktoren auf Adipositas/Übergewicht bei Kindern und Jugendlichen in Österreich

ZusammenfassungDas Ess- und Bewegungsverhalten unterliegt der Steuerungsfunktion durch bestimmte kognitive Muster. Es werden im Folgenden, zur Darstellung von eventuell durchgehenden Geschlechtertrends, die bei 4400 Kindern/Jugendlichen und 6600 Erwachsenen mit dem Adipositas Diagnostik- und Evalutionssystem (AD-EVA) gemessenen Unterschiede in der Teilgruppe der Adipösen dargestellt.Höhere Werte ungünstiger psychischer Steuerungsmechanismen des Ess- und Bewegungsverhaltens adipöser Mädchen liegen vor allem im Bereich der vorklinischen Essstörungen. Diese Ergebnisse sind für Prävention und Gesundheitsförderung relevant.Interessant sind auch die nicht-signifikanten Unterschiede im Bereich der Einstellung zu Bewegung wie der Bewegungsmotivation. Es würde bedeuten, dass man nicht dem Vorurteil aufsitzen darf, dass das männliche Geschlecht ohnehin mehr Freude an der Bewegung habe.Die männliche Vorliebe für „Snacks“ und „Deftiges“ konnte in der für Österreich repräsentativen Normstichprobe des Fragebogensystems AD-EVA repliziert werden, spiegelt sich aber nicht in der Teilgruppe der adipösen Mädchen und Knaben. Man kann davon ausgehen, dass sich 8- bis 18-jährige Adipöse beiderlei Geschlechts ungünstig ernähren.SummaryEating 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.

The Role of Vitamin D in atherosclerosis inflammation revisited. More bystander than player

Levels of 25-hydroxy vitamin D [25(OH)D] are reported to be decreased in cardiovascular disease (CVD) and in other chronic immunopathologies. Vitamin D (vitD) has been shown to be significantly linked to mortality, and is thought to be a predictor of survival. Therefore, supplementation with vitD has been suggested as an option to improve clinical outcomes. In contrast to the causal assumption, we hypothesize that the decreased vitD levels, seen in patients with CVD and chronic immunopathologies is secondary to inflammation and not as pathophysiologically relevant as currently suggested. Under these conditions, low vitD might be mainly caused by oxidative stress that results from chronic, immune-mediated vascular and systemic inflammation seen in patients with CVD. The oxidative environment most likely causes biodegradation of vitD and interferes with key enzymes, disturbing the biosynthesis of 25(OH)D and 1,25(OH)D. Thus far, no clear evidence of a beneficial effect of vitD supplements exists, beyond treating vitD deficiency to improve skeletal health. Moreover, a prolonged and/or high dose vitD supplementation, unless needed to correct actual vitD deficiency [levels of 25(OH)D<20 ng/ml)] may even be immunologically harmful by downregulating Th1 immune responses and indirectly upregulating Th2 immune activation with potential detrimental metabolic and cardiovascular effects. Large randomized controlled studies of vitD with multiple outcomes (skeletal, metabolic, cardiovascular and mental) are urgently needed.

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 (β = -12.3; 95% CI: -22.9, -1.8) and during OGTT (β = -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 (β = 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.