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ZusammenfassungAkute Stoffwechselentgleisungen können für Erwachsene in Abhängigkeit von ihrem Ausmaß lebensbedrohlich sein. Dementsprechend sind eine rasche umfassende Diagnostik und Therapie sowie eine enge Überwachung der Vitalparameter und Laborbefunde erforderlich. Bei der Therapie, die sich bei der ketoazidotischen (DKA) und hyperglykämisch-hyperosmolaren (HHS) Form nicht wesentlich unterscheidet, kommt dem Ausgleich des meist beträchtlichen Flüssigkeitsdefizits mit mehreren Litern einer physiologischen kristalloiden Lösung eine vorrangige Rolle zu. Bei den Elektrolyten ist insbesondere auf eine ausgeglichene Serum-Kalium-Konzentration zu achten. Normal-Insulin oder rasch wirksame Analoga können initial als i.v.-Bolus verabreicht werden, in der Folge jedoch kontinuierlich über einen Perfusor. Die Umstellung auf eine subkutane Insulintherapie soll erst bei ausgeglichenem Säure-Basen-Haushalt und zufriedenstellender Glykämie erfolgen.

ZusammenfassungDas vorliegende Positionspapier beschreibt die Sicht der Österreichischen Diabetes Gesellschaft hinsichtlich des perioperativen Managements von Menschen mit Diabetes mellitus auf Basis der verfügbaren wissenschaftlichen Evidenz. Dabei wird Bezug genommen auf die präoperative Begutachtung und Vorbereitung sowie auf die perioperative Stoffwechselkontrolle mittels oraler Antidiabetika und/oder injektabler Therapie (Insulin‑/GLP-1-RA-therapie).

ZusammenfassungDie Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt.

ZusammenfassungEpidemiologische Untersuchungen zeigen, dass etwa 2–3 % aller Österreicher*innen einen Diabetes mellitus mit Nierenbeteiligung aufweisen. Dies betrifft somit in Österreich etwa 250.000 Menschen. Das Risiko des Auftretens und Fortschreitens der diabetischen Nierenerkrankung kann durch Lebensstilinterventionen und Optimierung des arteriellen Blutdrucks, Blutzuckers und spezielle Medikamentenklassen vermindert werden. In diesem gemeinsamen Artikel der Österreichischen Gesellschaften für Nephrologie und Diabetologie werden die entsprechende Diagnostik und therapeutische Strategien bei diabetischer Nierenerkrankung vorgeschlagen.

ZusammenfassungBei der Beurteilung der gesundheitlichen Eignung zum Lenken eines Kraftfahrzeuges ist die öffentliche Sicherheit (Unfallprävention) das vorrangige Ziel. Der generelle Zugang zu Mobilität sollte jedoch nicht eingeschränkt werden, wenn kein besonderes Risiko für die öffentliche Sicherheit besteht. Für Menschen mit Diabetes mellitus sind im Führerscheingesetz (FSG) und in der Führerscheingesetz-Gesundheitsversorgung (FSG-GV) wichtige Aspekte zur Fahrsicherheit in Zusammenhang mit akuten und chronischen Komplikationen der Erkrankung geregelt. Zu den kritischen Komplikationen, die für die Verkehrssicherheit relevant sind, gehören schwere Hypoglykämie, ausgeprägte Hyperglykämie und Hypoglykämiewahrnehmungsstörung, sowie schwere Retinopathie und Neuropathie, weiters fortgeschrittene Nierenerkrankung und bestimmte kardiovaskuläre Manifestationen. Bei Verdacht auf Präsenz einer dieser Akutkomplikationen oder Folgeschäden ist eine genaue Evaluierung erforderlich.Darüber hinaus ist die individuelle antihyperglykämische Medikation auf vorhandenes Potenzial für Hypoglykämien zu überprüfen. Sulfonylharnstoffe, Glinide und Insulin gehören in diese Gruppe und sind daher automatisch mit der Auflage einer 5‑jährigen Befristung des Führerscheines assoziiert. Metformin, DPP-4-Hemmer (Dipeptidyl-Peptidase-4-Hemmer, Gliptine), SGLT2-Hemmer (Sodium-dependent-glucose-transporter‑2 inhibitors, Gliflozine), Glitazone und die zu injizierenden GLP-1 Analoga (GLP‑1 Rezeptor Agonisten) weisen kein Hypoglykämiepotential auf und sind daher nicht mit einer Befristung verbunden.Die FSG-GV gibt Spielraum für Interpretation, sodass im Folgenden spezifische Themen zur Fahrsicherheit für Menschen mit Diabetes mellitus aus fachärztlicher und verkehrsrelevanter Sicht aufgearbeitet wurden. Dieses Positionspapier dient zur Unterstützung von Personen, die mit dieser herausfordernden Materie befasst sind.

ZusammenfassungJe nach Diabetesform und -therapie sollen alle Menschen mit Diabetes eine individuelle ernährungsmedizinische Beratung und Schulung durch Fachpersonal erhalten. Im Vordergrund sollte eine patientinnen- und patientenzentrierte, individualisierte Beratung stehen, angepasst an die jeweiligen Bedürfnisse und Lebensumstände der Menschen mit Diabetes. Neben der Unterstützung zur Umsetzung einer ausgewogenen Ernährung gilt es, gemeinsam mit Patient:innen individuelle Stoffwechselziele und Gewichtsziele zu definieren, um mithilfe der Ernährung den Krankheitsverlauf positiv zu beeinflussen und mögliche Spätfolgen zu vermeiden. Dabei sollten vor allem praxisbezogene Empfehlungen unter Berücksichtigung der persönlichen Nahrungsmittel-Präferenzen ausgesprochen werden und Hilfsmittel zur Planung von geeigneten Portionsgrößen und der geeigneten Mahlzeitenzusammenstellung zum Einsatz kommen. Entsprechend aktueller internationaler und nationaler Standards sollen Menschen mit Diabetes im Diabetes-Selbstmanagement unterstützt werden (DSMES) und erlernen, die postprandiale Reaktion auf Speisen und Getränke besser einschätzen und durch die geeignete Lebensmittel- und Getränkeauswahl positiv beeinflussen zu können. Alle Menschen mit Diabetes sollten regelmäßig, je nach individuellem Bedarf, die Möglichkeit haben, eine ernährungstherapeutische Beratung oder Schulung in Anspruch nehmen zu können.Diese Praxisempfehlung stellt eine Zusammenfassung der aktuellen Literatur zu ernährungsrelevanten Aspekten bei Diabetes dar.

ZusammenfassungDer Body-Mass-Index (BMI) ist individuell betrachtet ein sehr grobes Maß für den Anteil des Körperfetts am Körpergewicht. Sogar Normalgewichtige können bei Muskelmangel zu viel Körperfett aufweisen (Sarkopenie), weswegen zusätzlich Messungen der Körperzusammensetzung (z. B. Bioimpedanzanalyse [BIA]) empfohlen werden. Lebensstilmanagement mit Ernährungsumstellung und Bewegung ist eine der wichtigsten Maßnahmen in der Diabetesprävention und -therapie. In der Therapie des Typ-2-Diabetes hat das Gewicht als sekundärer Zielparameter zunehmende Bedeutung erlangt. Auch die Wahl der antidiabetischen Therapie, aber auch der Begleittherapien nimmt immer mehr darauf Rücksicht. Die modernen GLP‑1 Analoga als auch der kombinierte GLP-1–GIP-Agonist Tirzepatid nehmen einen wichtigen Stellenwert in der gemeinsamen Behandlung von Adipositas und Diabetes mellitus Typ 2 ein. Die bariatrische Chirurgie ist derzeit bei an Diabetes mellitus Typ 2 erkrankten Menschen mit BMI > 35 kg/m2 indiziert und kann zumindest teilweise zur Diabetesremission beitragen, sie muss aber in ein entsprechendes lebenslanges Betreuungskonzept eingebunden sein.

ZusammenfassungDie unter der Kategorie „andere spezifische Diabetesformen“ zusammengefassten Störungen des Glukosestoffwechsels stellen pathophysiologisch und therapeutisch eine sehr heterogene Krankheitsgruppe dar. Umfasst werden Diabetesformen, die im Rahmen von anderen endokrinologischen Erkrankungen auftreten (z. B. Akromegalie, Cushing-Syndrom), medikamentös induzierte Diabetesformen (z. B. Antipsychotikatherapie, Glukokortikoidtherapie, HAART, Checkpoint-Inhibitoren, genetische Formen (z. B. i. R. eines MODY, neonataler Diabetes, Down-Syndrom, Klinefelter-Syndrom, Turner-Syndrom), pankreoprive Formen (z. B. postoperativ, Pankreatitis, Pankreastumoren, Hämochromatose, zystische Fibrose), Infektionen (z. B. kongenitale Rötelninfektion) und seltene autoimmune Formen (z. B. Stiffman-Syndrom). Die Diagnose der spezifischen Diabetesform kann die therapeutischen Erwägungen beeinflussen. Nicht nur pankreoprive Formen, sondern auch Typ 1 oder langjähriger Typ 2 Diabetes mellitus sind häufig mit einer exokrinen Pankreasinsuffizienz assoziiert.

ZusammenfassungDiabetesschulung und Selbstmanagement nehmen eine zentrale Rolle in der Diabetesbetreuung ein. Das dabei angestrebte Patient:innen-Empowerment zielt auf die aktive Beeinflussung des Diabetesverlaufs durch Selbstkontrolle und Therapieanpassung sowie die Befähigung der Betroffenen, den Diabetes in ihren Alltag zu integrieren und an ihre Lebensumstände entsprechend anzupassen. Eine Diabetesschulung ist allen Personen mit Diabetes zugänglich zu machen. Um ein strukturiertes und validiertes Schulungsprogramm anbieten zu können, sind adäquate personelle, räumliche, organisatorische und finanzielle Voraussetzungen nötig. Neben dem Zuwachs an Wissen über die Erkrankung konnte gezeigt werden, dass eine strukturierte Diabetesschulung ergebnisorientiert Parameter wie Blutzucker, HbA1c, Blutfette, Blutdruck und Körpergewicht positiv beeinflussen kann. Neuere Schulungsmodelle betonen neben der Ernährung die körperliche Bewegung als wichtigen Bestandteil der Lebensstil-Therapie und bedienen sich interaktiver Methoden, um die persönliche Verantwortung herauszuarbeiten. Spezifische Situationen (z. B. verminderte Hypoglykämie-Erkennung, Krankheit, Reisen), das Auftreten diabetischer Folgeerkrankungen und der Einsatz technischer Geräte wie Glukosesensor-Systeme und Insulinpumpen bedürfen zusätzlicher Schulungsmaßnahmen unterstützt durch adäquate elektronische Hilfsmittel (Diabetes-Apps, Diabetes-Web-Portale). Neue Erkenntnisse belegen den Nutzen telemedizinischer oder internetbasierter Dienste für die Diabetesprävention und das Diabetesmanagement.

ZusammenfassungDie Zusammenhänge zwischen Diabetes mellitus, koronarer Herzkrankheit und Herzinsuffizienz sind wechselseitig. Bei Erstmanifestation einer koronaren Herzkrankheit sollte aktiv auf Diabetes mellitus gescreent werden, während bei an Diabetes mellitus erkrankten Patient:innen die kardiovaskuläre Risikostratifizierung immer in Zusammenschau sämtlicher Risikofaktoren, Biomarker und dem klinischen Befinden des Patient:innen durchgeführt werden sollte. Eine bereits bekannte kardiovaskuläre Erkrankung wie auch das Vorliegen zahlreicher Risikofaktoren stellen wesentliche Kriterien für die Auswahl der individuellen Therapiestrategien dar.

ZusammenfassungEs besteht eine hohe Prävalenz an Diabetes mellitus Typ 2 bei über 70-Jährigen in industrialisierten Ländern. Dieser Artikel enthält Empfehlungen für Diagnose, Prävention und Therapieziele in der Behandlung älterer Menschen mit Diabetes anhand der aktuellen Evidenzlage.

Fibroblast growth factor 21 (FGF21) affects the regulation of metabolism. Additionally, anti-inflammatory properties are attributed to FGF21, and studies in animals and humans show conflicting results. This study aimed to investigate how FGF21 is affected by glucose and lipopolysaccharide (LPS) in humans. Therefore, FGF21 was measured eight times at different time points within 48 h in this prospective cross-over trial after glucose and LPS on two different study days. The study included ten healthy, non-smoking male subjects aged 18-40. Repeated measures analysis of variance and paired t-test as post hoc analysis were applied. The administration of glucose and LPS resulted in a significant difference in regulating FGF21 (p 0.001). After glucose administration, FGF21 declined sharply at 360 min, with a subsequent steep increase that exceeded baseline levels. LPS induced a drop in FGF21 after 180 min, while the baseline concentrations were not reached. After 180 min and 24 h, a statistically significant difference was demonstrated after adjusting the Bonferroni-Holm method. So, our results support the hypothesis that glucose and LPS differentially affect the human expression of FGF21 over 48 h.

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Background: Although vaccination against COVID-19 is highly effective, breakthrough infections occur, often leading to severe courses and death. The extent of protection provided by individual antibody levels in breakthrough infections is still unknown and cut-off levels have yet to be determined. Methods: In 80 consecutive fully vaccinated patients hospitalized between August and December 2021 with COVID-19 breakthrough infection (Delta variant), anti-CoV2S antibody levels were analyzed for the endpoint of death. Results: Ten out of the 12 patients who died (83.3%) had antibody levels < 600 U/mL; 5 (41.7%) of these had antibody levels < 200 U/mL. Only 2 patients with a level of >600 U/mL died from vaccine breakthrough infection. Correction for the number of comorbidities and age revealed that anti-CoV2S antibody levels at the time of hospitalization were a significant predictor for reduced risk of death (OR = 0.402 for every 1000 U/mL, p = 0.018). Conclusions: In this retrospective data analysis, we show that almost all patients who died from COVID-19 vaccine breakthrough infection had antibody levels < 600 U/mL, most of them below 200 U/mL. In logistic regression corrected for the number of comorbidities and age, anti-CoV2S antibody levels at the time of hospitalization proved to be a significantly protective predictor against death.

Acute infections are associated with an elevated cardiovascular risk. However, little is known about the interactions of acute inflammatory responses and the cardiovascular system. We therefore aimed to evaluate effects of acute inflammatory stimuli mediated by LPS administration on a set of 89 cardiovascular biomarkers. A single-blinded, placebo-controlled cross-over study using the human endotoxin model was performed. Ten healthy men were administered lipopolysaccharide (LPS) or placebo on two different study days after an overnight fast. Eighty-nine different cardiovascular biomarkers were measured repetitively over 48 h. Out of 89 cardiovascular biomarkers, 54 markers were significantly influenced by LPS infusion. The observed biomarker response to inflammation was more pronounced and complex than anticipated. In conclusion, our data show that the cardiovascular system is under enormous distress in response to experimental low-dose inflammation in humans, as demonstrated by a significant effect on 54 of the 89 biomarkers tested.

Background: Current means of diagnosis of acute kidney injury (AKI) based on serum creatinine have poor sensitivity and may miss possible therapeutic windows in subclinical kidney injury, especially in septic AKI. Kidney injury molecule-1 (KIM-1) may be a valuable biomarker to improve diagnostic algorithms for AKI. The understanding of septic AKI is still insufficient, and knowledge about KIM-1 kinetics in inflammation is scarce. The aim of this study was to investigate the possible effect of lipopolysaccharide (LPS) on KIM-1 as a marker of structural kidney injury in healthy volunteers. Methods: A single-blinded, placebo-controlled cross-over study using the human endotoxin model (LPS administration) was performed in 10 healthy men. Kidney injury molecule-1 and serum creatinine were measured repetitively for 48 hours. Results: We observed a significant elevation of serum KIM-1 levels after the administration of LPS ( P0.001). Furthermore, LPS caused a significant elevation of serum creatinine at an early time point ( P = 0.013) as compared with placebo. Conclusion: Even a relatively small inflammatory stimulus is sufficient to cause subclinical structural kidney injury with elevated KIM-1 and serum creatinine in healthy volunteers. This outlines the insufficiency of the current diagnostic approach regarding AKI and the urgency to develop novel diagnostic algorithms including markers of kidney injury. Clinical Trial Registration:www.clinicaltrials.gov . Unique identifier: NCT03392701 (August 1, 2018).

Highlights • Evaluation of EDITM ELISAs for detection of SARS-CoV-2 IgM and IgG in human plasma. • Antibodies were measured in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients. • with serial blood samples collected at different time points from symptom onset, • in 200 healthy blood donors, and in 256 intensive care unit patients. • High “true” vs. low “false” positivity rates for the SARS-CoV-2 IgM and IgG ELISAs., Background Besides SARS-CoV-2 RT-PCR testing, serological testing is emerging as additional option in COVID-19 diagnostics. Aim of this study was to evaluate novel immunoassays for detection of SARS-CoV-2 antibodies in human plasma. Methods Using EDITM Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. Results The positivity rates in the COVID-19 patients were 5.9% for IgM and 2.9% for IgG ≤5 days after symptom onset; Between day 5 and day 10 the positivity rates were 37.1% for IgM and 37.1% for IgG and rose to 76.4% for IgM and 82.4% for IgG after >10-15 days. After 15-22 days the “true” positivity rates were 94.4% for IgM and 100% for IgG. The “false” positivity rates were 0.5% for IgM and 1.0% for IgG in the healthy blood donors, 1.6% for IgM and 1.2% for IgG in ICU patients. Conclusions This study shows high “true” vs. low “false” positivity rates for the EDITM SARS-CoV-2 IgM and IgG ELISAs.

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Two review articles previously published from our working group were dedicated to the selection of endpoints as well as to reasons for premature stopping of randomized clinical trials (RCTs).1,2 We there first discussed the importance of mortality and morbidity endpoints vs. softer endpoints like revascularization rates and the issue of endpoint adjudication. Second, we have shed light on the statistical methods and requirements to stop RCTs prematurely due to safety, futility, or overwhelming efficacy (vs. the control arm).The main objective of this article is now to provide the clinical cardiologist with information how to judge and interpret published subgroup analyses. The next section will summarize the situation regarding subgroup analysis and put the current article in context.

Hypothesis Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals. Methods An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours. Results We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion. Conclusions Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1. Clinical trial registration NCT04488848.

Background Administration of lipopolysaccharide (LPS) from Gram-negative bacteria, also known as the human endotoxemia model, is a standardized and safe model of human inflammation. Experimental studies have revealed that peripheral administration of LPS leads to induction of the kynurenine pathway followed by depressive-like behavior and cognitive dysfunction in animals. The aim of the present study is to investigate how acute intravenous LPS administration affects the kynurenine pathway in healthy male human subjects. Methods The present study is a prospective, single-blinded, randomized, placebo-controlled cross-over study to investigate the effects of intravenously administered LPS (Escherichia coli O113, 2 ng/kg) on tryptophan and kynurenine metabolites over 48 h and their association with interleukin-6 (IL-6) and C-reactive protein (CRP). The study included 10 healthy, non-smoking men (18–40 years) free from medication. Statistical differences in tryptophan and kynurenine metabolites as well as associations with IL-6 and CRP in LPS and placebo treated subjects were assessed with linear mixed-effects models. Results Systemic injection of LPS was associated with significantly lower concentrations of plasma tryptophan and kynurenine after 4 h, as well as higher concentrations of quinolinic acid (QUIN) after 48 h compared to the placebo injection. No differences were found in kynurenic acid (KYNA) or picolinic acid plasma concentrations between LPS or placebo treatment. The KYNA/kynurenine ratio peaked at 6 h post LPS injection while QUIN/kynurenine maintained significantly higher from 3 h post LPS injection until 24 h. The kynurenine/tryptophan ratio was higher at 24 h and 48 h post LPS treatment. Finally, we report an association between the kynurenine/tryptophan ratio and CRP. Conclusions Our findings strongly support the concept that an inflammatory challenge with LPS induces the kynurenine pathway in humans, activating both the neurotoxic (QUIN) and neuroprotective (KYNA) branch of the kynurenine pathway. Trial registration This study is based on a study registered at ClinicalTrials.gov, NCT03392701. Registered 21 December 2017.

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.

Die Leitlinie nimmt Bezug auf die Diagnostik, einschlieslich begleitender Autoimmunerkrankungen, bei Typ 1 Diabetes mellitus, die Insulintherapie und die glykamischen Zielwerte.

Diabetes mellitus, cardiovascular disease and heart failure are interacting dynamically. Patients being diagnosed with cardiovascular disease should be screened for diabetes mellitus. Enhanced cardiovascular risk stratification based on biomarkers, symptoms and classical risk factors should be performed in patients with pre-existing diabetes mellitus. In patients with previously diagnosed arterosclerotic cardiovascular disease an agent proven to reduce major adverse cardiovascular events or cardiovascular mortality is recommended after therapy failure of metformin.

Zusammenfassung Akute Stoffwechselentgleisungen können für Erwachsene in Abhängigkeit von ihrem Ausmaß lebensbedrohlich sein. Dementsprechend sind eine rasche umfassende Diagnostik und Therapie sowie eine enge Überwachung der Vitalparameter und Laborbefunde erforderlich. Bei der Therapie, die sich bei der ketoazidotischen (DKA) und hyperglykämisch-hyperosmolaren (HHS) Form nicht wesentlich unterscheidet, kommt dem Ausgleich des meist beträchtlichen Flüssigkeitsdefizits mit mehreren Litern einer physiologischen kristalloiden Lösung eine vorrangige Rolle zu. Bei den Elektrolyten ist insbesondere auf eine ausgeglichene Serum-Kalium-Konzentration zu achten. Normal-Insulin oder rasch wirksame Analoga können initial als i.v.-Bolus verabreicht werden, in der Folge jedoch kontinuierlich über einen Perfusor. Die Umstellung auf eine subkutane Insulintherapie soll erst bei ausgeglichenem Säure-Basen-Haushalt und zufriedenstellender Glykämie erfolgen.

Diabetesschulung und Selbstmanagement nehmen eine zentrale Rolle in der Diabetesbetreuung ein. Das dabei angestrebte Patientenempowerment zielt auf die aktive Beeinflussung des Diabetesverlaufs durch Selbstkontrolle und Therapieanpassung sowie die Befahigung der Betroffenen, den Diabetes in ihren Alltag zu integrieren und an ihre Lebensumstande entsprechend anzupassen. Eine Diabetesschulung ist allen Personen mit Diabetes zuganglich zu machen. Um ein strukturiertes und validiertes Schulungsprogramm anbieten zu konnen, sind adaquate personelle, raumliche, organisatorische und finanzielle Voraussetzungen zu schaffen. Neben dem Zuwachs an Wissen uber die Erkrankung konnte gezeigt werden, dass eine strukturierte Diabetesschulung ergebnisorientiert Parameter wie Blutzucker, HbA1c, Blutdruck und Korpergewicht positiv beeinflussen kann. Neuere Schulungsmodelle betonen neben der Ernahrung die korperliche Bewegung als wichtigen Bestandteil der Lebensstiltherapie und bedienen sich interaktiver Methoden, um die personliche Verantwortung herauszuarbeiten. Spezifische Situationen (z. B. verminderte Hypoglykamieerkennung, Krankheit, Reisen) und technische Neuerungen wie Glukosesensorsysteme und Insulinpumpen bedurfen zusatzlicher Schulungsmasnahmen durch Informationsaustausch in Kleingruppen, unterstutzt durch adaquate elektronische Hilfsmittel (Diabetes-Apps, Diabetes-Web-Portale).

Recent epidemiological investigations have shown that approximately 2-3% of all Austrians suffer from diabetes with renal involvement, i. e. 250,000 people in Austria are affected. The risk of occurrence and progression of this disease can be ameliorated by life style interventions as well as optimization of blood pressure, blood glucose levels and special drug classes. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society for Nephrology for the diagnostics and treatment strategies of diabetic kidney disease.

Die vorliegende Leitlinie nimmt Bezug auf die Indikation und praktische Umsetzung der Insulintherapie bei Typ 2 Diabetes, insbesondere auch im Hinblick auf die unterschiedlichen Formen der Insulintherapie.

Das vorliegende Positionspapier beschreibt die Sicht der Osterreichischen Diabetes Gesellschaft hinsichtlich des perioperativen Managements von Patienten mit Diabetes mellitus auf Basis der verfugbaren wissenschaftlichen Evidenz. Dabei wird Bezug genommen auf die praoperative Begutachtung und Vorbereitung sowie auf die perioperative Stoffwechselkontrolle mittels oraler Antidiabetika und/oder injektabler Therapie (Insulin-/GLP-1-RA-therapie).

Die unter der Kategorie „andere spezifische Diabetesformen“ zusammengefassten Storungen des Glukosestoffwechsels stellen pathophysiologisch und therapeutisch eine sehr heterogene Krankheitsgruppe dar. Umfasst werden Diabetesformen, die im Rahmen von anderen endokrinologischen Erkrankungen auftreten (z. B. Akromegalie, Cushing-Syndrom), pankreoprive Formen (z. B. postoperativ, Pankreatitis, Pankreastumoren, Hamochromatose, zystische Fibrose), medikamentos induzierte Diabetesformen (z. B. Antipsychotikatherapie, Glukokortikoidtherapie, HAART), genetische Formen (z. B. i. R. eines MODY, neonataler Diabetes, Down-Syndrom, Klinefelter-Syndrom, Turner-Syndrom), Infektionen (z. B. kongenitale Rotelninfektion) und seltene autoimmune Formen (z. B. Stiffman-Syndrom). Nicht nur pankreoprive Formen, sondern auch Typ 1 oder langjahriger Typ 2 Diabetes mellitus sind haufig mit einer exokrinen Pankreasinsuffizienz assoziiert.

Background and aims Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. Methods and results In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35–63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. Conclusion We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.

Background Recently, the European Society of Cardiology (ESC) and European Association for the Society of Diabetes (EASD) introduced a new cardiovascular disease (CVD) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to investigate the prognostic performance of the ESC/EASD risk model in comparison to the Systematic COronary Risk Evaluation (SCORE) risk model and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected cohort of type 2 diabetes mellitus (T2DM). Methods and results A total of 1690 T2DM patients with a 10-year follow up for fatal CVD and all-cause death and a 5-year follow up for CVD and all-cause hospitalizations were analyzed. According to ESC/EASD risk criteria 25 (1.5%) patients were classified as moderate, 252 (14.9%) high, 1125 (66.6%) very high risk and 288 (17.0%) were not classifiable. Both NT-proBNP and SCORE risk model were associated with 10-year CVD and all-cause death and 5-year CVD and all-cause hospitalizations while the ESC/EASD model was only associated with 10-year all-cause death and 5-year all-cause hospitalizations. NT-proBNP and SCORE showed significantly higher C-indices than the ESC/EASD risk model for CVD death [0.80 vs. 0.53, p Conclusion The new introduced ESC/EASD risk stratification model performed limited compared to SCORE and single NT-proBNP assessment for predicting 10-year CVD and all-cause fatal events in individuals with T2DM.

Background. Recently, the European Society of Cardiology (ESC) and European Association for the Society of Diabetes (EASD) introduced a new cardiovascular disease (CVD) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to investigate the prognostic performance of the ESC/EASD risk model and the Systematic COronary Risk Evaluation (SCORE) in comparison to NT-proBNP in an unselected cohort of type 2 diabetes mellitus (T2DM).Methods & Results. A total of 1690 T2DM patients with a 10-year follow up for fatal CVD and all-cause death and a 5-year follow up for CVD and all-cause hospitalizations were analyzed. According to ESC/EASD risk criteria 25 (1.5%) patients were classified as moderate, 252 (14.9%) high, 1125 (66.6%) very high risk and 288 (17.0%) were not classifiable. Both, NT-proBNP and SCORE risk model were associated with 10-year CVD and all-cause death and 5-year CVD and all-cause hospitalizations while the ESC/EASD model was only associated with 10-year all-cause death and 5-year all-cause hospitalizations. NT-proBNP showed significantly higher C-indices than the ESC/EASD and SCORE risk model for CVD death [0.80 vs 0.53 vs 0.64, pConclusion. The new introduced ESC/EASD risk stratification model performed limited compared to SCORE and single NT-proBNP assessment for predicting 10-year CVD and all-cause fatal events in individuals with T2DM.

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.

AIMWe assessed predictors of in-hospital mortality in people with prediabetes and diabetes hospitalized for COVID-19 infection and developed a risk score for identifying those at the highest risk of a fatal outcome.MATERIALS AND METHODSA combined prospective and retrospective multicenter cohort study was conducted in 10 sites in Austria on 247 people with diabetes or newly diagnosed prediabetes, who were hospitalised for COVID-19. The primary outcome was in-hospital mortality and predictor variables at the time of admission included clinical data, comorbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and develop a risk score for in-hospital mortality.RESULTSThe 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. Mortality rate in people with diabetes was numerically higher (26.7%) as compared to those with prediabetes (14.9%) but without statistical significance (p=0.128). A score including age, arterial occlusive disease, CRP, eGFR and AST levels at admission predicted in-hospital mortality with a C-statistics of 0.889 (95%CI: 0.837 – 0.941) and calibration of 1.000 (p=0.909).CONCLUSIONSThe in-hospital mortality for COVID-19 was high in people with diabetes and not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient parameters demonstrated excellent predictive performance for assessing in-hospital mortality.

Background Recently, the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) introduced a new cardiovascular (CV) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to validate the ESC/EASD CV risk assessment in type 2 diabetes mellitus (T2DM) patients for the first time and to compare the prognostic significance of NT-proBNP with the ESC/EASD CV risk stratification model. Methods and results We prospectively included 2186 T2DM patients with a follow-up of 60 months. Patients were stratified according to ESC/EASD CV risk criteria, 33 (1.5%) were classified as moderate, 321 (14.9%) high and 1453 (67.6%) very high risk. Both, the ESC/EASD risk stratification model and NT-proBNP were associated with CV outcome (CV events: adj. HR: 1.47 [1.09–1.98], p=0.011 and adj. HR per IQR: 2.61 [2.27–3.01], p Conclusion NT-proBNP measurement provides a valid tool to identify T2DM patients at risk and shows superiority in terms of risk prediction and discriminatory power compared to the ESC/EASD CV assessment. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant from the Austrian Science Fund

Background. Recently, the European Society of Cardiology (ESC) and European Association for the Society of Diabetes (EASD) introduced a new cardiovascular (CV) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to investigate the prognostic performance of NT-proBNP and the Systematic COronary Risk Evaluation (SCORE) compared to the ESC/EASD risk model in an unselected cohort of type 2 diabetes mellitus (T2DM).Methods & Results. A total of 1690 T2DM patients with a 10-year follow up for fatal CV and all-cause death and a 5-year follow up for CV and all-cause hospitalizations were analyzed. According to ESC/EASD risk criteria 25 (1.5%) patients were classified as moderate, 252 (14.9%) high, 1125 (66.6%) very high risk and 288 (17.0%) were not classifiable. NT-proBNP, the ESC/EASD and SCORE risk model were all associated with 10-year CV and all-cause death and 5-year CV and all-cause hospitalizations. NT-proBNP showed significantly higher C-indices than the ESC/EASD and SCORE risk model for CV death [0.80 vs 0.53 vs 0.64, pConclusion. NT-proBNP is a high-performing biomarker for CV risk assessment in T2DM. Single NT-proBNP is superior compared to SCORE and the multiparameter ESC/EASD risk stratification model for predicting 10-year CV and all-cause fatal events.

Lipoproteins, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9), have been shown to play a key role in the innate immune response. However, knowledge about the role and kinetics of PCSK9 in human inflammation is currently insufficient. This study aimed to investigate the interaction between inflammation and lipid metabolism, including the possible role of PCSK9. A single-blinded, placebo-controlled cross-over study using the human endotoxin model was performed., Lipoproteins, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9), have been shown to play a key role in the innate immune response. However, knowledge about the role and kinetics of PCSK9 in human inflammation is currently insufficient. This study aimed to investigate the interaction between inflammation and lipid metabolism, including the possible role of PCSK9. A single-blinded, placebo-controlled cross-over study using the human endotoxin model was performed. Ten healthy men received lipopolysaccharide (LPS) or placebo on two different study days after overnight fasting. Lipoproteins as well as PCSK9 were measured repetitively over 48 h. PCSK9 plasma concentrations were not induced by LPS infusion, and no correlation between PCSK9 plasma concentrations and the degree of inflammation could be identified. The observed low-density lipoprotein (LDL) response to inflammation was more complex than anticipated, especially in the very early phase after the inflammatory stimulus. Baseline concentrations of LDL, as well as high-density lipoprotein (HDL), correlated negatively with inflammatory response. Our data suggest that the lipoprotein response to inflammation is independent of PCSK9. The proposed elevations of PCSK9 and suspected correlations between PCSK9 levels and inflammatory response are not supported by our data. (This study has been registered at ClinicalTrials.gov under registration no. NCT03392701.)

Hyper- und Dyslipidamie tragen zur kardiovaskularen Morbiditat und Mortalitat diabetischer Patienten bei. Uberzeugende Daten zeigen, dass eine medikamentose Therapie mit Statinen das kardiovaskulare Risiko von Patienten mit Diabetes senken kann. Der vorliegende Artikel stellt die Behandlungsvorschlage der Osterreichischen Diabetes Gesellschaft zum Einsatz lipidsenkender Medikamente dar.

Bei kritisch kranken Patienten kommt es haufig zum Auftreten einer Hyperglykamie, welche eindeutig mit einer gesteigerten Mortalitatsrate assoziiert ist. Der aktuell verfugbaren Datenlage entsprechend sollte eine intravenose Insulintherapie bei Blutzuckerwerten >180 mg/dl begonnen werden und ein Zielbereich zwischen meist 140–180 mg/dl angestrebt werden.