Martin Clodi - Academia.edu (original) (raw)
Papers by Martin Clodi
International Journal of Molecular Sciences
Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is... more Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is a phenomenon that is increasingly becoming the target of scientific attention when it comes to increased risk of coronary heart disease. Effects of GV may contribute to the development of metabolic syndrome and type 2 diabetes. Hyperglycemia can lead to oxidative stress resulting in molecular damage due to accumulation of reactive oxygen species (ROS). To discover more about the immediate effects of GV, continuous vs. bolus intravenous glucose administration was applied to 10 healthy men aged 21–30 years over a time frame of 48 h. Whole blood and plasma were analyzed for DNA damage using a comet assay with 3 different treatments (lysis buffer, H2O2, and the lesion-specific enzyme formamidopyrimidine DNA glycosylase (FPG)) as well as for the oxidative stress markers protein carbonyls (PC), unconjugated bilirubin (UCB), and ferric reducing antioxidant power (FRAP). A significant time effe...
International Journal of Environmental Research and Public Health
Background: Although vaccination against COVID-19 is highly effective, breakthrough infections oc... more 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 retr...
Wiener klinische Wochenschrift
ZusammenfassungDer Body-Mass-Index (BMI) ist individuell betrachtet ein sehr grobes Maß für den A... more 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 i...
Wiener klinische Wochenschrift
ZusammenfassungDiabetesschulung und Selbstmanagement nehmen eine zentrale Rolle in der Diabetesbe... more 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...
Wiener klinische Wochenschrift
ZusammenfassungBei kritisch kranken PatientInnen kommt es häufig zum Auftreten einer Hyperglykämi... more ZusammenfassungBei kritisch kranken PatientInnen kommt es häufig zum Auftreten einer Hyperglykämie welche eindeutig mit einer gesteigerten Mortalitätsrate assoziiert ist. Der aktuell verfügbaren Datenlage entsprechend sollte eine intravenöse Insulintherapie bei Blutzuckerwerten > 180 mg/dl begonnen werden und ein Zielbereich zwischen meist 140–180 mg/dl angestrebt werden.
Wiener klinische Wochenschrift
ZusammenfassungJe nach Diabetesform und -therapie sollen alle Menschen mit Diabetes eine individu... more 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...
Wiener Klinische Wochenschrift, 2019
Diabetes Care, 2022
OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney ... more OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS...
Diabetes, Obesity and Metabolism, 2020
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phas... more 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.
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier ph... more 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.
BASIC/TRANSLATIONAL/CLINICAL - Late Breaking Research in Endocrinology, 2011
Wiener klinische Wochenschrift, 2019
Geriatric aspects for the management of diabetes mellitus (Update 2019) Summary There is a high p... more Geriatric aspects for the management of diabetes mellitus (Update 2019) Summary 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.
Wiener klinische Wochenschrift, 2019
Zusammenfassung Bei kritisch kranken Patienten kommt es häufig zum Auftreten einer Hyperglykämie,... more Zusammenfassung Bei kritisch kranken Patienten kommt es häufig zum Auftreten einer Hyperglykämie, welche eindeutig mit einer gesteigerten Mortalitätsrate assoziiert ist. Der aktuell verfügbaren Datenlage entsprechend sollte eine intravenöse Insulintherapie bei Blutzuckerwerten >180 mg/dl begonnen werden und ein Zielbereich zwischen meist 140-180 mg/dl angestrebt werden.
Endocrine Abstracts, 2016
Heart (British Cardiac Society), Oct 25, 2016
Based on previous experiences, the Food and Drug Administration and the European Medicines Agency... more Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels. 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proB...
Molecular and Cellular Biology, 1999
Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) ... more Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) and the subsequent formation of phosphatidylinositides (PtdIns) 3,4-P2 and PtdIns 3,4,5-P3, which are thought to be involved in signaling for glucose transporter GLUT4 translocation, cytoskeletal rearrangement, and DNA synthesis. However, the specific role of each of these PtdIns in insulin and growth factor signaling is still mainly unknown. Therefore, we assessed, in the current study, the effect of SH2-containing inositol phosphatase (SHIP) expression on these biological effects. SHIP is a 5′ phosphatase that decreases the intracellular levels of PtdIns 3,4,5-P3. Expression of SHIP after nuclear microinjection in 3T3-L1 adipocytes inhibited insulin-induced GLUT4 translocation by 100 ± 21% (mean ± the standard error) at submaximal (3 ng/ml) and 64 ± 5% at maximal (10 ng/ml) insulin concentrations ( P < 0.05 and P < 0.001, respectively). A catalytically inactive mutant of SHIP had...
Diabetologie kompakt, 2014
2.1 Leitlinien der Deutschen Diabetes Gesellschaft (DDG)-34 2.2 Leitlinien der Österreichischen D... more 2.1 Leitlinien der Deutschen Diabetes Gesellschaft (DDG)-34 2.2 Leitlinien der Österreichischen Diabetes Gesellschaft-36 2.3 Richtlinien der Schweizerischen Gesellschaft für Endokrinologie und Diabetologie-40 2.4 Betreuungsprogramme in Deutschland am Beispiel des Disease-Management-Programms (DMP)-45 2.5 Betreuungsprogramme in Österreich-47 2.6 Betreuungsprogramme in der Schweiz-48 2.7 Leitlinien der IDF und ADA/EASD-49 2.8 Versorgungsforschung und Evaluation-51 Literatur-53
International Journal of Molecular Sciences
Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is... more Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is a phenomenon that is increasingly becoming the target of scientific attention when it comes to increased risk of coronary heart disease. Effects of GV may contribute to the development of metabolic syndrome and type 2 diabetes. Hyperglycemia can lead to oxidative stress resulting in molecular damage due to accumulation of reactive oxygen species (ROS). To discover more about the immediate effects of GV, continuous vs. bolus intravenous glucose administration was applied to 10 healthy men aged 21–30 years over a time frame of 48 h. Whole blood and plasma were analyzed for DNA damage using a comet assay with 3 different treatments (lysis buffer, H2O2, and the lesion-specific enzyme formamidopyrimidine DNA glycosylase (FPG)) as well as for the oxidative stress markers protein carbonyls (PC), unconjugated bilirubin (UCB), and ferric reducing antioxidant power (FRAP). A significant time effe...
International Journal of Environmental Research and Public Health
Background: Although vaccination against COVID-19 is highly effective, breakthrough infections oc... more 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 retr...
Wiener klinische Wochenschrift
ZusammenfassungDer Body-Mass-Index (BMI) ist individuell betrachtet ein sehr grobes Maß für den A... more 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 i...
Wiener klinische Wochenschrift
ZusammenfassungDiabetesschulung und Selbstmanagement nehmen eine zentrale Rolle in der Diabetesbe... more 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...
Wiener klinische Wochenschrift
ZusammenfassungBei kritisch kranken PatientInnen kommt es häufig zum Auftreten einer Hyperglykämi... more ZusammenfassungBei kritisch kranken PatientInnen kommt es häufig zum Auftreten einer Hyperglykämie welche eindeutig mit einer gesteigerten Mortalitätsrate assoziiert ist. Der aktuell verfügbaren Datenlage entsprechend sollte eine intravenöse Insulintherapie bei Blutzuckerwerten > 180 mg/dl begonnen werden und ein Zielbereich zwischen meist 140–180 mg/dl angestrebt werden.
Wiener klinische Wochenschrift
ZusammenfassungJe nach Diabetesform und -therapie sollen alle Menschen mit Diabetes eine individu... more 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...
Wiener Klinische Wochenschrift, 2019
Diabetes Care, 2022
OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney ... more OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS...
Diabetes, Obesity and Metabolism, 2020
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phas... more 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.
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier ph... more 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.
BASIC/TRANSLATIONAL/CLINICAL - Late Breaking Research in Endocrinology, 2011
Wiener klinische Wochenschrift, 2019
Geriatric aspects for the management of diabetes mellitus (Update 2019) Summary There is a high p... more Geriatric aspects for the management of diabetes mellitus (Update 2019) Summary 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.
Wiener klinische Wochenschrift, 2019
Zusammenfassung Bei kritisch kranken Patienten kommt es häufig zum Auftreten einer Hyperglykämie,... more Zusammenfassung Bei kritisch kranken Patienten kommt es häufig zum Auftreten einer Hyperglykämie, welche eindeutig mit einer gesteigerten Mortalitätsrate assoziiert ist. Der aktuell verfügbaren Datenlage entsprechend sollte eine intravenöse Insulintherapie bei Blutzuckerwerten >180 mg/dl begonnen werden und ein Zielbereich zwischen meist 140-180 mg/dl angestrebt werden.
Endocrine Abstracts, 2016
Heart (British Cardiac Society), Oct 25, 2016
Based on previous experiences, the Food and Drug Administration and the European Medicines Agency... more Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels. 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proB...
Molecular and Cellular Biology, 1999
Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) ... more Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) and the subsequent formation of phosphatidylinositides (PtdIns) 3,4-P2 and PtdIns 3,4,5-P3, which are thought to be involved in signaling for glucose transporter GLUT4 translocation, cytoskeletal rearrangement, and DNA synthesis. However, the specific role of each of these PtdIns in insulin and growth factor signaling is still mainly unknown. Therefore, we assessed, in the current study, the effect of SH2-containing inositol phosphatase (SHIP) expression on these biological effects. SHIP is a 5′ phosphatase that decreases the intracellular levels of PtdIns 3,4,5-P3. Expression of SHIP after nuclear microinjection in 3T3-L1 adipocytes inhibited insulin-induced GLUT4 translocation by 100 ± 21% (mean ± the standard error) at submaximal (3 ng/ml) and 64 ± 5% at maximal (10 ng/ml) insulin concentrations ( P < 0.05 and P < 0.001, respectively). A catalytically inactive mutant of SHIP had...
Diabetologie kompakt, 2014
2.1 Leitlinien der Deutschen Diabetes Gesellschaft (DDG)-34 2.2 Leitlinien der Österreichischen D... more 2.1 Leitlinien der Deutschen Diabetes Gesellschaft (DDG)-34 2.2 Leitlinien der Österreichischen Diabetes Gesellschaft-36 2.3 Richtlinien der Schweizerischen Gesellschaft für Endokrinologie und Diabetologie-40 2.4 Betreuungsprogramme in Deutschland am Beispiel des Disease-Management-Programms (DMP)-45 2.5 Betreuungsprogramme in Österreich-47 2.6 Betreuungsprogramme in der Schweiz-48 2.7 Leitlinien der IDF und ADA/EASD-49 2.8 Versorgungsforschung und Evaluation-51 Literatur-53