[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.

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients.

OBJECTIVE: The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe a real-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals. METHODS: Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type 9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using a Monte Carlo simulation. RESULTS: A cohort of patients (N = 144) with a mean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with a decrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall. CONCLUSIONS: The SANTORINI real-world data in Austria suggest that a proportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

[Other specific types of diabetes and exocrine pancreatic insufficiency (update 2023)]. / Andere spezifische Diabetesformen und exokrine Pankreasinsuffizienz (Update 2023).

The heterogenous category "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e.g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART), checkpoint inhibitors), genetic forms of diabetes (e.g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down­, Klinefelter- and Turner Syndrome), pancreatogenic diabetes (e.g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

[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.

[Lipids-Diagnosis and therapy in diabetes mellitus (Update 2023)]. / Lipide: Diagnostik und Therapie bei Diabetes mellitus (Update 2023).

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

[Inhibition of platelet aggregation (Update 2023)]. / Thrombozytenaggregationshemmer (Update 2023).

Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in patients with diabetes. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in patients with diabetes according to current scientific evidence.

Patient adherence to fully reimbursed proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) treatment.

AIMS: Proprotein convertase subtilisin/kexin-type 9 inhibitor (PCSK9i) treatment reduces cardiovascular events when taken over a long time for secondary prevention. Data on treatment adherence are scarce and maybe affected by co-payment of patients. The aim of this study was to elucidate PCSK9i treatment adherence in a setting of full cost coverage as it is the case in a number of European countries. METHODS AND RESULTS: Baseline data and prescription patterns of all 7302 patients with PCSK9i prescriptions dispensed on the account of Austrian Social Insurances between September 2015 and December 2020 were retrieved and analyzed. A gap of ≥ 60 days between prescriptions was defined as treatment discontinuation. Patient adherence was evaluated as the proportion of days covered (PDC) over the observation period and treatment discontinuation rates were investigated by the Kaplan-Meier method. The mean PDC was 81.8% and was significantly lower in female patients. A PDC of ≥ 80% indicating adequate adherence was found in 73.8%. Of the study population 27.4% discontinued PCSK9i treatment and 49.2% thereof re-initiated treatment during the observation period. Most of the patients who discontinued treatment did so within the first year. Male patients and patients under 64 years showed significantly lower discontinuation and higher re-initiation rates. CONCLUSION: Considering the high PDC and low discontinuation rates, the majority of patients adhere to PCSK9i treatment. Hence, in a system where PCSK9i treatment is made available at virtually no costs for patients this highly effective treatment is well-accepted as a long-term treatment.

Biomarkers Predictive for In-Hospital Mortality in Patients with Diabetes Mellitus and Prediabetes Hospitalized for COVID-19 in Austria: An Analysis of COVID-19 in Diabetes Registry.

BACKGROUND: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. METHODS: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. RESULTS: In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate (p = 0.302), while it was inadequate for Troponin T (p = 0.010). CONCLUSION: Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients.

Long-term eliglustat treatment of Gaucher patients over up to 10 years in Vienna.

Gaucher disease has been the first lysosomal storage disorder for which an enzyme replacement therapy has been approved in the 1990s and was the first to receive approval for a first-line substrate reduction therapy in 2015. Eliglustat treatment has been started in Austria in patients recruited to a clinical trial, followed by its long-term extension and prescription treatment overall covering up to 10 years. In this case series the experience of treating Gaucher patients with eliglustat in Vienna is summarized. Patients were either switched from enzyme replacement therapy or were therapy naïve. Significant improvements were shown in hematological (thrombocytes, hemoglobin) and visceral (spleen volume) manifestations as well as in biomarkers (chitotriosidase, glucosylsphingosine [lyso-GL1], angiotensin converting enzyme) in a routine setting in a therapy-naïve patient. Stability was found in switch patients with slight improvement in bone density. Eliglustat was generally very well tolerated. Patient selection and regular monitoring is required to ensure effective and safe use.

Thrombin cleavage of osteopontin initiates osteopontin's tumor-promoting activity.

BACKGROUND: Osteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and metastases. Thrombin cleavage of OPN reveals a cryptic binding site for α4 ß1 and α9 ß1 integrins. METHODS: Thrombin cleavage-resistant OPNR153A knock-in (OPN-KI) mice were generated and compared to OPN deficient mice (OPN-KO) and wild type (WT) mice in their ability to support growth of melanoma cells. Flow cytometry was used to analyze tumor infiltrating leukocytes. RESULTS: OPN-KI mice engineered with a thrombin cleavage-resistant OPN had reduced B16 melanoma growth and fewer pulmonary metastases than WT mice. The tumor suppression phenotype of the OPN-KI mouse was identical to that observed in OPN-KO mice and was replicated in WT mice by pharmacologic inhibition of thrombin with dabigatran. Tumors isolated from OPN-KI mice had increased tumor-associated macrophages with an altered activation phenotype. Immunodeficient OPN-KI mice (NOG-OPN-KI) or macrophage-depleted OPN-KI mice did not exhibit the tumor suppression phenotype. As B16 cells do not express OPN, thrombin-cleaved fragments of host OPN suppress host antitumor immune response by functionally modulating the tumor-associated macrophages. YUMM3.1 cells, which express OPN, showed less tumor suppression in the OPN-KI and OPN-KO mice than B16 cells, but its growth was suppressed by dabigatran similar to B16 cells. CONCLUSIONS: Thrombin cleavage of OPN, derived from the host and the tumor, initiates OPN's tumor-promoting activity in vivo.

100 years of inherited metabolic disorders in Austria-A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021.

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the "Registry for Inherited Metabolic Disorders" started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000-113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months-100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the "Registry for Inherited Metabolic Disorders" is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.

Diabetes and COVID-19: What 2 Years of the Pandemic Has Taught Us.

As the world enters its third year of the COVID-19 pandemic, individuals with diabetes have faced particular challenges from the virus. A deleterious bidirectional relationship exists between the two disorders, with heightened inflammatory, immunologic, and cellular mechanisms leading to a more severe illness and increased morbidity and mortality. Tight glucose control, though necessary, is hampered by physical restrictions and difficulty accessing health care. Novel glucose-lowering medications may provide unique benefits in this regard. It is imperative that multi-pronged efforts be prioritized in order to reduce adverse outcomes in patients with diabetes at risk for COVID-19.

COVID-19 In-Hospital Mortality in People with Diabetes Is Driven by Comorbidities and Age-Propensity Score-Matched Analysis of Austrian National Public Health Institute Data.

BACKGROUND: It is a matter of debate whether diabetes alone or its associated comorbidities are responsible for severe COVID-19 outcomes. This study assessed the impact of diabetes on intensive care unit (ICU) admission and in-hospital mortality in hospitalized COVID-19 patients. METHODS: A retrospective analysis was performed on a countrywide cohort of 40,632 COVID-19 patients hospitalized between March 2020 and March 2021. Data were provided by the Austrian data platform. The association of diabetes with outcomes was assessed using unmatched and propensity-score matched (PSM) logistic regression. RESULTS: 12.2% of patients had diabetes, 14.5% were admitted to the ICU, and 16.2% died in the hospital. Unmatched logistic regression analysis showed a significant association of diabetes (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.15-1.34, p < 0.001) with in-hospital mortality, whereas PSM analysis showed no significant association of diabetes with in-hospital mortality (OR: 1.08, 95%CI: 0.97-1.19, p = 0.146). Diabetes was associated with higher odds of ICU admissions in both unmatched (OR: 1.36, 95%CI: 1.25-1.47, p < 0.001) and PSM analysis (OR: 1.15, 95%CI: 1.04-1.28, p = 0.009). CONCLUSIONS: People with diabetes were more likely to be admitted to ICU compared to those without diabetes. However, advanced age and comorbidities rather than diabetes itself were associated with increased in-hospital mortality in COVID-19 patients.

COVID-19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission.

AIM: To assess predictors of in-hospital mortality in people with prediabetes and diabetes hospitalized for COVID-19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome. MATERIALS AND METHODS: A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID-19. The primary outcome was in-hospital mortality and the predictor variables upon admission included clinical data, co-morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in-hospital mortality. RESULTS: The mean age of people hospitalized (n = 238) for COVID-19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P = .128). A score including age, arterial occlusive disease, C-reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in-hospital mortality with a C-statistic of 0.889 (95% CI: 0.837-0.941) and calibration of 1.000 (P = .909). CONCLUSIONS: The in-hospital mortality for COVID-19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in-hospital mortality.

Diabetes and COVID-19 : Disease-Management-People.

The current pandemic of SARS-CoV­2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.

Impact of osteopontin on the development of non-alcoholic liver disease and related hepatocellular carcinoma.

BACKGROUND & AIMS: Osteopontin, a multifunctional protein and inflammatory cytokine, is overexpressed in adipose tissue and liver in obesity and contributes to the induction of adipose tissue inflammation and non-alcoholic fatty liver (NAFL). Studies performed in both mice and humans also point to a potential role for OPN in malignant transformation and tumour growth. To fully understand the role of OPN on the development of NAFL-derived hepatocellular carcinoma (HCC), we applied a non-alcoholic steatohepatitis (NASH)-HCC mouse model on osteopontin-deficient (Spp1-/- ) mice analysing time points of NASH, fibrosis and HCC compared to wild-type mice. METHODS: Two-day-old wild-type and Spp1-/- mice received a low-dose streptozotocin injection in order to induce diabetes, and were fed a high-fat diet starting from week 4. Different cohorts of mice of both genotypes were sacrificed at 8, 12 and 19 weeks of age to evaluate the NASH, fibrosis and HCC phenotypes respectively. RESULTS: Spp1-/- animals showed enhanced hepatic lipid accumulation and aggravated NASH, as also increased hepatocellular apoptosis and accelerated fibrosis. The worse steatotic and fibrotic phenotypes observed in Spp1-/- mice might be driven by enhanced hepatic fatty acid influx through CD36 overexpression and by a pathological accumulation of specific diacylglycerol species during NAFL. Lack of osteopontin lowered systemic inflammation, prevented HCC progression to less differentiated tumours and improved overall survival. CONCLUSIONS: Lack of osteopontin dissociates NASH-fibrosis severity from overall survival and HCC malignant transformation in NAFLD, and is therefore a putative therapeutic target only for advanced chronic liver disease.

Aquaporin regulation in metabolic organs.

Aquaporins (AQPs) are a family of 13 small trans-membrane proteins, which facilitate shuttling of glycerol, water and urea. The peculiar role of AQPs in glycerol transport makes them attractive targets in metabolic organs since glycerol represents the backbone of triglyceride synthesis. Importantly, AQPs are known to be regulated by various nuclear receptors which in turn govern lipid and glucose metabolism as well as inflammatory cascades. Here, we review the role of AQPs regulation in metabolic organs exploring their physiological impact in health and disease.

Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice.

PURPOSE OF REVIEW: A considerable body of data from genetic and epidemiological studies strongly support a causal relationship between high lipoprotein(a) [Lp(a)] levels, and the development of atherosclerosis and cardiovascular disease. This relationship is continuous, unrelated to Lp(a) threshold, and independent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. Unfortunately, the mechanism(s) through which Lp(a) promotes atherosclerosis are not clarified yet. Suggested hypotheses include: an increased Lp(a)-associated cholesterol entrapment in the arterial intima followed by inflammatory cell recruitment, abnormal upload of proinflammatory oxidized phospholipids, impaired fibrinolysis by inhibition of plasminogen activation, and enhanced coagulation, through inhibition of the tissue factor pathway inhibitor. This review is aimed at summarizing the available evidence on the topic. RECENT FINDINGS: There are two clinical forms, isolated hyperlipidemia(a) [HyperLp(a)] with acceptable LDL-C levels (< 70 mg/dL), and combined elevation of Lp(a) and LDL-C in plasma. To date, no drugs that selectively decrease Lp(a) are available. Some novel lipid-lowering drugs can lower Lp(a) levels, but to a limited extent, as their main effect is aimed at decreasing LDL-C levels. Significant Lp(a) lowering effects were obtained with nicotinic acid at high doses. However, adverse effects apart, nicotinic acid is no longer prescribed and available in Europe for clinical use, after European Agency of Medicines (EMA) ban. The only effective therapeutic option for now is Lipoprotein Apheresis (LA), albeit with some limitations. Lastly, it is to be acknowledged that the body of evidence confirming that reducing plasma isolated elevation of Lp(a) brings cardiovascular benefit is still insufficient. However, the growing bulk of clinical, genetic, mechanistic, and epidemiological available evidence strongly suggests that Lp(a) is likely to be the smoking gun.

[Lipids-Diagnosis and therapy in diabetes mellitus (Update 2019)]. / Lipide: Diagnostik und Therapie bei Diabetes mellitus (Update 2019).

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.