General Practice for Internal Medicine

Bruck an der Mur, Austria

General Practice for Internal Medicine

Bruck an der Mur, Austria
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Mangge H.,Medical University of Graz | Prassl R.,Medical University of Graz | Haara A.,Innsbruck Medical University | Schnedl W.,General Practice for Internal Medicine | And 2 more authors.
Current Vascular Pharmacology | Year: 2015

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. © 2015 Bentham Science Publishers.

Pruller F.,Medical University of Graz | Raggam R.B.,Medical University of Graz | Posch V.,Medical University of Graz | Almer G.,Medical University of Graz | And 6 more authors.
Atherosclerosis | Year: 2012

Objective: Endogenous thrombin generation (ETP) may be critically involved in obesity associated thromboembolism. Methods: Three hundred and one participants of the STyrian Juvenile OBesity (STYJOBS)/Early DEteCTion of Atherosclerosis (EDECTA) study cohort (age, 16-58years) were analysed. ETP was measured by the new CE-IVD marked Siemens-Innovance ® ETP test on a BCS-XP analyser, and correlated to clinical findings and extended lipometry-based anthropometric data, biomarkers, and coagulation parameters. Results: In the overweight/obese study group, ETP and fibrinogen levels were significantly higher compared to controls (p< 0.001). In a multiple stepwise regression including all subjects, subcutaneous adipose tissue thickness of upper back, cholesterol and ultrasensitive C-reactive protein were the best predictors for ETP. Conclusion: Trunk weighted obesity together with low grade inflammation and hypercholesterolemia enhance thrombin generation. © 2011 Elsevier Ireland Ltd.

Mangge H.,Medical University of Graz | Summers K.L.,Medical University of Graz | Meinitzer A.,Medical University of Graz | Zelzer S.,Medical University of Graz | And 5 more authors.
Obesity | Year: 2014

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. Copyright © 2013 The Obesity Society.

Zelzer S.,Medical University of Graz | Stelzer I.,Medical University of Graz | Schnedl W.,General Practice for Internal Medicine | Molnar D.,University of Pécs | Mangge H.,Medical University of Graz
Experimental and Clinical Endocrinology and Diabetes | Year: 2013

Background: Since obesity and its associated co-morbidities do not only have effect on the individual patient, but also on society and the health system, it is of great importance to investigate this lifestyle-disease. The rationale of this study was to distinguish metabolically healthy from unhealthy overweight/obese patients as compared to healthy normal weight children and adolescents by means of a comprehensive anthropometric, laboratory and sonomorphological vascular assessment. Material and methods: 299 study participants were derived from the prospective, observational study STYJOBS/EDECTA (STYrian Juvenile Obesity Study/Early DEteCTion of Arteriosclerosis). Standard anthropometric data were obtained for each subject. This study comprised different diagnostic steps: extended anthropometry (Lipometer®), carotid artery ultrasound, various laboratory measurements, blood pressure measurement, oral glucose tolerance test. Ow/ob juveniles were classified as "metabolically healthyo" (no laboratory criteria of metabolic syndrome fulfilled) vs. "metabolically unhealthyo" (≥ 3 criteria of metabolic syndrome). Results underwent statistical evaluation, including t-test or Mann-Whitney U-test, regression analysis and a p-value < 0.05 was considered statistically significant. Results and Discussion: In the study's central European cohort only about 16% (n=48/299) of the overweight/obese juveniles can be regarded as metabolically healthy. About 36% (n=108/299) of the overweight/obese patients fulfilled the criteria for metabolic syndrome. High visceral fat stores (p<0.001) and their clinical surrogate waist circumference (p<0.001) determine an adverse metabolic phenotype. Several parameters, including uric acid (p<0.001), adiponectin (p<0.05), insulin resistance (HOMA-Index, p<0.001), nuchal SAT thickness (p<0.001), arteriosclerosis of the carotids (p<0.001), and others are responsible for the distinction between metabolically healthy and unhealthy juveniles. Nevertheless, "healthy obesityo" only defines a sub-phenotype of a disease effecting rising numbers of young patients. Conclusion: Since obesity in children and adolescents is not a consistent entity, it remains crucial to differ between metabolically healthy and unhealthy obese children in order to achieve appropriate intervention and prevention for our patients. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart New York.

Zelzer S.,Medical University of Graz | Fuchs N.,Medical University of Graz | Almer G.,Medical University of Graz | Raggam R.B.,Medical University of Graz | And 8 more authors.
Clinica Chimica Acta | Year: 2011

Background: Obesity related dyslipidemia, chronic inflammation and oxidative stress were associated with atherosclerotic sequels. We analysed oxidized low-density lipoprotein (oxLDL) plasma levels of 797 participants of the STyrian Juvenile OBesity (STYJOBS) / Early DEteCTion of Atherosclerosis (EDECTA) Study cohort aged from 5 to 50 years. The rationale of STYJOBS/EDECTA is to investigate the preclinical phase of obesity by a well defined cohort of young and middle aged overweight/obese and normal weight subjects. Methods and Results: Plasma oxLDL was analysed by ELISA (Mercodia, Sweden). In the overweight/obese (OW/OB) study group, oxLDL levels were significantly increased compared to normal weighted controls (p < 0.001). Probands with metabolic syndrome (MS) had significantly higher oxLDL levels than probands without MS; between overweight and obese participants, and between females and males, no significant difference was seen. In a multiple stepwise regression analysis including all study subjects, age, gender, anthropometric data, presence of metabolic syndrome, systolic, diastolic blood pressure, carotis communis intima media thickness, lipids, adipokines, metabolic, and inflammatory biomarkers, decreased high-density lipoprotein (HDL-cholesterol) and increased total cholesterol were the best predictors for increased oxLDL levels. Conclusion: Decreased HDL-cholesterol is an important determinant of lipid peroxidation irrespective of obesity, age, gender, SAT distribution, and inflammatory/metabolic biomarkers. © 2011 Elsevier B.V.

Mangge H.,Medical University of Graz | Zelzer S.,Medical University of Graz | Meinitzer A.,Medical University of Graz | Stelzer I.,Medical University of Graz | And 8 more authors.
Current Pharmaceutical Design | Year: 2015

Contradictory results exist for levels of vitamin D measured in patients with cardiovascular disease (CVD), obesity and metabolic syndrome (MetS). To clarify this, we investigated 527 participants of the STYJOBS/ EDECTA cohort (NCT00482924)[1], with ages between 10 and 65 years. A cross-sectional analysis of anthropometry, carotid intima media thickness (IMT), and laboratory measurements for 25OH-Vitamin D3 (vitD), glucose metabolism, ultra-sensitive C-reactive protein (US-CRP), interleukin-6 (IL-6), lipids, liver-, renal-parameters, and kynurenine to tryptophan ratio were made for a selection of persons who were either obese or of normal weight. The homeostasis model assessment insulin resistance (HOMA) was also measured. As compared to the normal weight controls, significantly decreased blood levels of vitD were found in overweight/obese adults, which were not observed in the juveniles. Nevertheless, both overweight/obese juveniles and adults had significantly increased US-CRP, IL-6, HOMA, triglyceride, and LDL-cholesterol levels, and significantly decreased HDL-cholesterol levels. Juveniles with MetS displayed unchanged levels of vitD as compared to overweight/obese juveniles without MetS. Although IMT was significantly increased in both juvenile and adult overweight/obese subjects, vitD and IMT levels were not correlated. Assuming a minimum threshold of 20 ng/ml for the establishment of “low” or “normal” vitD levels, no significant alteration in IMT, metabolic, and inflammatory markers was observed in juveniles with a low vitD-status . In conclusion, although metabolic and inflammatory symptoms of obesity are displayed in juveniles, their vitD levels are unaffected. This, together with the complete lack of association with carotid IMT in both juveniles and adults, argues against a causative role of vitD in obesity-associated vascular pathology. © 2015 Bentham Science Publishers.

Mangge H.,Medical University of Graz | Zelzer S.,Medical University of Graz | Puerstner P.,Medical University of Graz | Schnedl W.J.,General Practice for Internal Medicine | And 3 more authors.
Obesity | Year: 2013

Objective: The obesity prevalence is growing worldwide and largely responsible for cardiovascular disease, the most common cause of death in the western world. The rationale of this study was to distinguish metabolically healthy from unhealthy overweight/obese young and adult patients as compared to healthy normal weight age matched controls by an extensive anthropometric, laboratory, and sonographic vascular assessment. Design and Methods: Three hundred fifty five young [8 to ≤ 18 years, 299 overweight/obese(ow/ob), 56 normal weight (nw)] and 354 adult [>18-60 years, 175 (ow/ob), 179 nw)] participants of the STYJOBS/EDECTA (STYrian Juvenile Obesity Study/Early DEteCTion of Atherosclerosis) cohort were analyzed. STYJOBS/ EDECTA (NCT00482924) is a crossectional study to investigate metabolic/cardiovascular risk profiles in normal and ow/ob people free of disease exceptmetabolic syndrome (MetS). Results: From 299 young ow/ob subjects (8-≤ 18 years), 108 (36%), and from 175 adult ow/ob subjects (>18-60 years), 79 (45%) had positive criteria for MetS. In both age groups, prevalence of MetS was greater among males. Overweight/obese subjects were divided into "healthy" (no MetS criterion except anthropometry fulfilled) and "unhealthy" (MetS positive). Although percentage body fat did not differ between "healthy" and "unhealthy" ow/ob, nuchal and visceral fat were significantly greater in the "unhealthy" group which had also significantly higher values of carotid intima media thickness (IMT). With MetS as the dependent variable, two logistic regressions including juveniles ≤18 years or adults >18 years were performed. The potential predictor variables selected with the exception of age and gender by t test comparisons included IMT, ultrasensitive c-reactive protein (US-CRP), IL-6, malondialdehyde (MDA), oxidized LDL, leptin, adiponectin, uric acid (UA), aldosterone, cortisol, transaminases, fibrinogen. In both groups, uric acid and in adults only, leptin and adiponectin, turned out as the best predictor. Conclusion: Serum levels of UA are a significant predictor of unhealthy obesity in juveniles and adults.

Mangge H.,Medical University of Graz | Baumgartner B.G.,Paracelsus Medical University | Zelzer S.,Medical University of Graz | Pruller F.,Medical University of Graz | And 7 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2015

Background Obesity is associated with non-alcoholic fatty liver disease (NAFLD), and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene polymorphism is one of the most important genetic determinants of NAFLD. Carriers have been reported to better respond to lifestyle modification. Aim To investigate the effect of rs738409 on overweight/obese adolescents and adults with and without metabolic syndrome (MetS). Methods Two hundred and eighty-eight overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort (NCT00482924) were analysed for PNPLA3 genotypes. Results Compared to overweight/obese without MetS, in overweight/obese study participants with MetS, the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs. 9.2%, Spearman's correlation, 0.12; P = 0.038). Persons with CG (heterozygote for the risk allele) and with GG (homozygote for the risk allele) genotypes showed significantly higher ALT levels than those with CC genotypes. Even young individuals aged below 20 years had significantly increased ALT levels if they were homozygote with the G allele. Conclusions The PNPLA3 rs738409 polymorphism is associated already in youths with increased ALT, and is more frequent in obese with MetS of all ages. Hence, overweight/obese rs738409 carriers should be identified early in life and treated with a rigorous life style intervention. © 2015 John Wiley & Sons Ltd.

Mangge H.,Medical University of Graz | Summers K.,Medical University of Graz | Almer G.,Medical University of Graz | Prassl R.,Medical University of Graz | And 3 more authors.
Current Medicinal Chemistry | Year: 2013

The obesity prevalence is growing worldwide and largely responsible for the increased incidence of cardiovascular disease, the most common cause of death in the western world. Excessive food intake along with insufficient physical exercise is the basic impetus for this development. The obese state is commonly associated with an increase in leptin levels and chronic immune-mediated inflammation. Despite high leptin levels, the leptin response, normally associated with satiety and satiation, seems to be impaired and individuals continue to consume calorie-rich food. Antioxidant food additives such as sodium sulphite, sodium benzoate and curcumin were shown to suppress the leptin release in lipopolysaccharide- treated murine adipocytes. Based on this, we hypothesize that the insufficient leptin release, caused by excessive consumption of food additives, may lead to a reduced exposure of the central nervous system to leptin and ultimately propagate obesity. On the other hand, leptin has been shown to favor Th1-type activity, which ultimately decreases tryptophan levels. Tryptophan derivatives, serotonin and melatonin, induce satiety/satiation through several mechanisms. In this context, the antioxidant suppression of leptin release and Th1-type activity is beneficial to increase serotonin and melatonin levels. The molecules in the mechanism described in this review are highly integrated in the reward system, and have been implicated in the addiction behavior of obesity. Based on these facts, the involvement of antioxidant food supplements in the mechanisms of the reward-deficiency syndrome which perpetuates obesity will be discussed. © 2013 Bentham Science Publishers.

PubMed | General Practice for Internal Medicine, Medical University of Graz, General Hospital Steyr, Uppsala University and Paracelsus Medical University
Type: | Journal: The Journal of nutritional biochemistry | Year: 2016

Cardiovascular risk is increased in obese subjects. Nevertheless, some overweight and obese remain cardiometabolically healthy (CMH), and normal-weight persons develop cardiovascular disease (CVD). Herein, we investigate the potential of branched-chain amino acids (BCAAs) to identify an increased CVD risk in a cross-sectional study of 666 adults and juveniles (age 25.312.8years), classified as lean, overweight or obese. Cardiometabolic groups were defined by cutoffs of systolic blood pressure<130mmHg, diastolic blood pressure<85mmHg, glucose<125mg/dl, triglycerides<150mg/dl, HDL-cholesterol>40mg/dl (males), HDL-cholesterol>50mg/dl (females) and HOMA-IR<5. CMH had 1 cutoff, and cardiometabolically abnormal (CMA) had 2 cutoffs. Amino acids were measured by high-pressure lipid chromatography after precipitation of serum with perchloric acid and derivatization with o-phthalaldehyde. Valine correlated with 5, leucine correlated with 3 and isoleucine correlated with 5 of the cardiac risk classification factors. Valine and leucine were significantly higher in the obese (P<.001, P=.015, respectively), overweight (P<.001, P=.015, respectively) and lean (P=.024, P=.012, respectively) CMA compared to CMH subjects. Isoleucine showed except of the lean group the same results. Taken together, BCAAs, especially valine and leucine, are proposed as a cardiometabolic risk marker independent of body mass index (BMI) category.

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