[Overweight and obesity in adults: general principles of treatment and conservative management]. / Übergewicht und Adipositas bei Erwachsenen: allgemeine Behandlungsgrundsätze und konservatives Management.

The prevalence of overweight and obesity is steadily increasing in Austria as well as internationally. Obesity in particular is associated with multiple health risks, comorbidities, functional disability, and social stigma. Obesity is an independent, complex, chronic disease and should be treated as such by a multidisciplinary team of appropriately qualified personnel. In addition to recent international guidelines, this consensus paper outlines the overall principles of the management of overweight and obesity and provides guidance for the diagnosis and conservative treatment, focusing on lifestyle modifications and pharmacotherapy. Using the "5A" framework of behavioral health intervention, guidelines for a structured, pragmatic, and patient-centered medical care of adults with overweight or obesity are presented.

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2023)]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2 (Update 2023).

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

[Position statement: surgery and diabetes mellitus (Update 2023)]. / Positionspapier: Operation und Diabetes mellitus (Update 2023).

This position statement reflects the perspective of the Austrian Diabetes Association concerning the perioperative management of people with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antihyperglycemic and/or insulin therapy.

[Geriatric aspects for the management of diabetes mellitus (Update 2023)]. / Geriatrische Aspekte bei Diabetes mellitus (Update 2023).

There is a high prevalence of diabetes mellitus in the elderly population of industrial countries. The present article provides recommendations for the screening, prevention and treatment of elderly diabetic patients according to current scientific evidence.

[Insulin therapy of type 2 diabetes mellitus (Update 2019)]. / Insulintherapie bei Typ 2 Diabetes mellitus (Update 2019).

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2019)]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2 (Update 2019).

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

[Position statement: surgery and diabetes mellitus (Update 2019)]. / Positionspapier: Operation und Diabetes mellitus (Update 2019).

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

[Geriatric aspects for the management of diabetes mellitus (Update 2019)]. / Geriatrische Aspekte bei Diabetes mellitus (Update 2019).

There is a high prevalence of diabetes mellitus in the elderly population of industrial countries. The present article provides recommendations for the screening, prevention and treatment of elderly diabetic patients according to current scientific evidence.

[Geriatric aspects for the management of diabetes mellitus]. / Geriatrische Aspekte bei Diabetes mellitus.

There is a high prevalence of diabetes mellitus in the elderly population of industrial countries. The present article provides recommendations for the screening, prevention and treatment of elderly diabetic patients according to current scientific evidence.

[Position statement: surgery and diabetes mellitus]. / Positionspapier: Operation und Diabetes mellitus.

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

[Position statement: Surgery and diabetes mellitus]. / Positionspapier: Operation und Diabetes mellitus.

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

[Geriatric aspects for the management of diabetes mellitus]. / Geriatrische Aspekte bei Diabetes mellitus.

There is a high incidence of Diabetes mellitus in the elderly population of industrial countries. The present article provides recommendations for the screening, prevention and treatment of elderly diabetic patients according to current scientific evidence.

Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients.

Accumulation of cytotoxic and T-helper (T(h))1 cells together with a loss of regulatory T cells in gonadal adipose tissue was recently shown to contribute to obesity-induced adipose tissue inflammation and insulin resistance in mice. Human data on T-cell populations in obese adipose tissue and their potential functional relevance are very limited. We aimed to investigate abundance and proportion of T-lymphocyte sub-populations in human adipose tissue in obesity and potential correlations with anthropometric data, insulin resistance, and systemic and adipose tissue inflammation. Therefore, we analyzed expression of marker genes specific for pan-T cells and T-cell subsets in visceral and subcutaneous adipose tissue from highly obese patients (BMI >40 kg/m(2), n = 20) and lean to overweight control subjects matched for age and sex (BMI <30 kg/m(2); n = 20). All T-cell markers were significantly upregulated in obese adipose tissue and correlated with adipose tissue inflammation. Proportions of cytotoxic T cells and T(h)1 cells were unchanged, whereas those of regulatory T cells and T(h)2 were increased in visceral adipose tissue from obese compared to control subjects. Systemic and adipose tissue inflammation positively correlated with the visceral adipose abundance of cytotoxic T cells and T(h)1 cells but also regulatory T cells within the obese group. Therefore, this study confirms a potential role of T cells in human obesity-driven inflammation but does not support a loss of protective regulatory T cells to contribute to adipose tissue inflammation in obese patients as suggested by recent animal studies.

CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity.

BACKGROUND/AIMS: Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined. METHODS: sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression. RESULTS: Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression. CONCLUSION: Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.

Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations.

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.

Specific monocyte adhesion to endothelial cells induced by oxidized phospholipids involves activation of cPLA2 and lipoxygenase.

Oxidized phospholipids stimulate endothelial cells to bind monocytes, but not neutrophils, an initiating event in atherogenesis. Here, we investigate intracellular signaling events induced by oxidized phospholipids in human umbilical vein endothelial cells (HUVECs) that lead to specific monocyte adhesion. In a static adhesion assay, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and one of its components, 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine, stimulated HUVECs to bind U937 cells and human peripheral blood monocytes but not HL-60 cells or blood neutrophils. Monocyte adhesion was dependent on protein kinases A and C, extracellular signal-regulated kinase 1/2, p38 mitogen activated protein kinases (MAPKs), and cytosolic phospholipase A(2) (cPLA(2)). Inhibition of 12-lipoxygenase (12-LOX), but not cyclooxygenases, blocked monocyte adhesion, and addition of 12-hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized phospholipids. Peroxisome proliferator-activated receptor alpha (PPARalpha) was excluded as a possible target for 12-HETE, because monocyte adhesion was still induced in endothelial cells from PPARalpha null mice. Together, our results suggest that oxidized phospholipids stimulate HUVECs to specifically bind monocytes involving MAPK pathways, which lead to the activation of cPLA(2) and 12-LOX. Further analysis of signaling pathways induced by oxidized phospholipids that lead to specific monocyte adhesion should ultimately lead to the development of novel therapeutic approaches against chronic inflammatory diseases.

Apoptotic cells as sources for biologically active oxidized phospholipids.

Acute inflammation is characterized by an accumulation of polymorphonuclear cells (PMNs), generation of reactive oxygen species, subsequent apoptosis of PMNs, and finally phagocytosis of apoptotic cells by macrophages. Recently, it has been demonstrated that during apoptosis oxidation of membrane phospholipids, especially phosphatidylserine, occurs. Moreover, we have shown that membrane vesicles released from apoptotic cells contain biologically active oxidized phospholipids. The involvement of oxidized phospholipids in the development of atherosclerosis, which is described as a chronic inflammatory disease, is increasingly recognized. These oxidized phospholipids were shown to induce several proinflammatory genes, such as monocyte chemoattractant protein 1 or interleukin-8, and it is hypothesized that lipid oxidation products also play a role in other chronic inflammatory disorders. On the other hand, oxidized phospholipids were shown to exert antiendotoxin effects by inhibiting lipopolysaccharide-induced signaling, representing a possible feedback loop during gram-negative infection. Additionally, it has been described that oxidized phospholipids are capable of inducing genes such as heme oxygenase-1 that are important for the resolution of acute inflammation. Moreover, oxidized phospholipids serve as recognition signals on apoptotic cells facilitating phagocytosis. In this review, we discuss the hypothesis that oxidized phospholipids generated in apoptotic cells (a) propagate chronic inflammation and (b) contribute to the resolution of acute inflammation.

Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of cAMP-responsive element-binding protein.

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, protects against oxidative stress, and shows potent anti-inflammatory effects. Oxidized phospholipids, which are generated during inflammation and apoptosis, modulate the inflammatory response by inducing the expression of several genes including HO-1. Here we investigated the signaling pathways and transcriptional events involved in the induction of HO-1 gene expression by oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) in human umbilical vein endothelial cells. OxPAPC up-regulated HO-1 mRNA and protein in a time- and concentration-dependent manner, whereas pro-inflammatory agents like TNF-alpha and lipopolysaccharide did not significantly induce HO-1 expression in human umbilical vein endothelial cells. Signaling pathways involved in the OxPAPC-mediated HO-1 induction included protein kinases A and C, as well as the mitogen-activated protein kinases p38 and ERK. The cAMP-responsive element-binding protein (CREB) was phosphorylated via these pathways in response to OxPAPC treatment and expression of a dominant-negative mutant of CREB inhibited OxPAPC-induced activity of a human heme oxygenase-1 promoter-driven luciferase reporter construct. We identified a cAMP-responsive element and a Maf recognition element to be involved in the transcriptional activation of the HO-1 promoter by OxPAPC. In gel shift assays we observed binding of CREB to the cAMP-responsive element after OxPAPC treatment. Induction of HO-1 expression by lipid oxidation products via CREB may represent a feedback mechanism to limit inflammation and associated tissue damage.

The isoprostane 8-iso-PGE2 stimulates endothelial cells to bind monocytes via cyclic AMP- and p38 MAP kinase-dependent signaling pathways.

Increased levels of isoprostanes have been detected in human atherosclerotic lesions. To examine a possible role for 8-iso-prostaglandin E(2) (8-iso-PGE(2)) in atherogenesis, we tested the effect of 8-iso-PGE(2) on adhesion of leukocytes to human umbilical vein endothelial cells (EC). We demonstrate that 8-iso-PGE(2) stimulates EC to bind monocytes, but not neutrophils. This effect was inhibited by the thromboxane A(2) receptor antagonist SQ29548. Moreover, 8-iso-PGE(2) increased levels of cyclic AMP in EC, and monocyte adhesion induced by 8-iso-PGE(2) was blocked by a protein kinase A inhibitor, H89. In addition, 8-iso-PGE(2 )induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein (MAP) kinase and stimulated expression of EGR-1. A specific inhibitor of p38 MAP kinase (SB203580) abrogated monocyte binding, whereas an inhibitor of the ERK pathway (PD98059) did not block monocyte adhesion induced by 8-iso-PGE(2). Activation of nuclear factor-kappaB (NF-kappaB) and expression of NFkappaB-dependent genes intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin were not induced by 8-iso-PGE(2). Taken together, these results demonstrate that 8-iso-PGE(2) stimulates EC to specifically bind monocytes, but not neutrophils. This effect is mediated by cyclic AMP/protein kinase A- and p38 MAP kinase-dependent pathways and is independent of the classical inflammatory NFkappaB pathway. Thus, formation of 8-iso-PGE(2) may play an important role in chronic inflammatory diseases such as atherosclerosis by increasing adhesion and extravasation of monocytes.