165 results on '"Eberhard, A."'
Search Results
2. CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes
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Oliver Schnell, Katharine Barnard-Kelly, Tadej Battelino, Antonio Ceriello, Helena Elding Larsson, Beatriz Fernández-Fernández, Thomas Forst, Juan-Pablo Frias, James R. Gavin, Francesco Giorgino, Per-Henrik Groop, Hiddo J. L. Heerspink, Stephan Herzig, Michael Hummel, George Huntley, Mahmoud Ibrahim, Baruch Itzhak, Stephan Jacob, Linong Ji, Mikhail Kosiborod, Nebosja Lalic, Sofia Macieira, Rayaz A. Malik, Boris Mankovsky, Nikolaus Marx, Chantal Mathieu, Timo D. Müller, Kausik Ray, Helena W. Rodbard, Peter Rossing, Lars Rydén, Petra-Maria Schumm-Draeger, Peter Schwarz, Jan Škrha, Frank Snoek, Frank Tacke, Bruce Taylor, Britta Tendal Jeppesen, Solomon Tesfaye, Pinar Topsever, Tina Vilsbøll, Xuefeng Yu, and Eberhard Standl
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Cardiovascular disease ,Chronic kidney disease ,CGM ,Diabetes ,Finerenone ,GLP-1 RA ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5–6, 2024 ( http://www.cvot.org ).
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- 2024
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3. CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes
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Schnell, Oliver, Battelino, Tadej, Bergenstal, Richard, Birkenfeld, Andreas L., Ceriello, Antonio, Cheng, Alice, Davies, Melanie, Edelman, Steve, Forst, Thomas, Giorgino, Francesco, Green, Jennifer, Groop, Per-Henrik, Hadjadj, Samy, J.L.Heerspink, Hiddo, Hompesch, Marcus, Izthak, Baruch, Ji, Linong, Kanumilli, Naresh, Mankovsky, Boris, Mathieu, Chantal, Miszon, Martin, Mustafa, Reem, Nauck, Michael, Pecoits-Filho, Roberto, Pettus, Jeremy, Ranta, Kari, Rodbard, Helena W., Rossing, Peter, Ryden, Lars, Schumm-Draeger, Petra-Maria, Solomon, Scott D., Škrha, Jan, Topsever, Pinar, Vilsbøll, Tina, Wilding, John, and Standl, Eberhard
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- 2023
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4. CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes
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Oliver Schnell, Tadej Battelino, Richard Bergenstal, Andreas L. Birkenfeld, Antonio Ceriello, Alice Cheng, Melanie Davies, Steve Edelman, Thomas Forst, Francesco Giorgino, Jennifer Green, Per-Henrik Groop, Samy Hadjadj, Hiddo J.L.Heerspink, Marcus Hompesch, Baruch Izthak, Linong Ji, Naresh Kanumilli, Boris Mankovsky, Chantal Mathieu, Martin Miszon, Reem Mustafa, Michael Nauck, Roberto Pecoits-Filho, Jeremy Pettus, Kari Ranta, Helena W. Rodbard, Peter Rossing, Lars Ryden, Petra-Maria Schumm-Draeger, Scott D. Solomon, Jan Škrha, Pinar Topsever, Tina Vilsbøll, John Wilding, and Eberhard Standl
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Cardiovascular disease ,Chronic kidney disease ,Diabetes ,GIP/GLP-1 receptor agonist ,Heart failure ,Obesity ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10–12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year’s focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23–24, 2023 ( http://www.cvot.org ).
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- 2023
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5. Report from the CVOT Summit 2021: new cardiovascular, renal, and glycemic outcomes
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Schnell, Oliver, Battelino, Tadej, Bergenstal, Richard, Blüher, Matthias, Böhm, Michael, Brosius, Frank, Carr, Richard D., Ceriello, Antonio, Forst, Thomas, Giorgino, Francesco, Guerci, Bruno, Heerspink, Hiddo J. L., Itzhak, Baruch, Ji, Linong, Kosiborod, Mikhail, Lalić, Nebojša, Lehrke, Michael, Marx, Nikolaus, Nauck, Michael, Rodbard, Helena W., Rosano, Giuseppe M. C., Rossing, Peter, Rydén, Lars, Santilli, Francesca, Schumm-Draeger, Petra-Maria, Vandvik, Per Olav, Vilsbøll, Tina, Wanner, Christoph, Wysham, Carol, and Standl, Eberhard
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- 2022
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6. Report from the CVOT Summit 2021: new cardiovascular, renal, and glycemic outcomes
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Oliver Schnell, Tadej Battelino, Richard Bergenstal, Matthias Blüher, Michael Böhm, Frank Brosius, Richard D. Carr, Antonio Ceriello, Thomas Forst, Francesco Giorgino, Bruno Guerci, Hiddo J. L. Heerspink, Baruch Itzhak, Linong Ji, Mikhail Kosiborod, Nebojša Lalić, Michael Lehrke, Nikolaus Marx, Michael Nauck, Helena W. Rodbard, Giuseppe M. C. Rosano, Peter Rossing, Lars Rydén, Francesca Santilli, Petra-Maria Schumm-Draeger, Per Olav Vandvik, Tina Vilsbøll, Christoph Wanner, Carol Wysham, and Eberhard Standl
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Diabetes ,Cardiovascular disease ,Heart failure ,Chronic kidney disease ,Obesity ,SGLT2 inhibitor ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18–19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year’s focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1–5, and STEP 1–5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed. Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10–11, 2022 ( http://www.cvot.org )
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- 2022
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7. The benefits of ventriculoperitoneal shunting in normal pressure hydrocephalus patients—a follow-up of three years.
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Gencer, Aylin H., Schwarm, Frank P., Nagl, Jasmin, Uhl, Eberhard, and Kolodziej, Malgorzata A.
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HYDROCEPHALUS ,DIABETES ,STATISTICAL correlation ,CEREBROVASCULAR disease ,VALVES ,CEREBROSPINAL fluid shunts - Abstract
Objective: The ventriculoperitoneal shunt (VPS) is an established approach in treating normal pressure hydrocephalus (NPH). This study aims to examine the long-term effects of VPS regarding clinical and radiological outcomes, to explore interdependencies with comorbidities and medication, and to determine a suitable opening pressure of the programmable valve. Methods: 127 patients with VPS were retrospectively evaluated. The Hakim triad along with Evans index (EI) and callosal angle (CA) were examined preoperatively and postoperatively at various time points up to over thirty-six months. Preexisting comorbidities and medication were considered. Adjustments to valve settings were documented along with symptom development and complications. Wilcoxon and paired-sample t-tests were used to analyze postoperative change. Chi-square, Eta-squared, and Pearson coefficients were used in correlation analyses. Results: Relief from individual symptoms was most prominent within the first 6 months (p < 0.01). EI and CA significantly decreased and increased, respectively (p < 0.05). Postoperative clinical and radiological improvement was largely maintained over the follow-up period. Diabetes mellitus and apoplexy correlated with surgical outcomes (p < 0.05). The median opening pressure as a function of overall symptom management was determined to be 120 mmH
2 O for women and 140 mmH2 O for men. Conclusion: VPS is effective in treating NPH with respect to both clinical and radiological outcomes, although these two components are independent of each other. Improvement is most pronounced in short-term and maintained in the long-term. Comorbidities have significant influence on the course of NPH. The valve setting does not forecast change in radiological findings; consequently, priority should be placed on the patient's clinical condition. [ABSTRACT FROM AUTHOR]- Published
- 2024
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8. Regulation of Transporters for Organic Cations by High Glucose
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Martin Steinbüchel, Johannes Menne, Rita Schröter, Ute Neugebauer, Eberhard Schlatter, and Giuliano Ciarimboli
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organic cation transporters ,glucose ,regulation ,diabetes ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Endogenous positively charged organic substances, including neurotransmitters and cationic uremic toxins, as well as exogenous organic cations such as the anti-diabetic medication metformin, serve as substrates for organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs). These proteins facilitate their transport across cell membranes. Vectorial transport through the OCT/MATE axis mediates the hepatic and renal excretion of organic cations, regulating their systemic and local concentrations. Organic cation transporters are part of the remote sensing and signaling system, whose activity can be regulated to cope with changes in the composition of extra- and intracellular fluids. Glucose, as a source of energy, can also function as a crucial signaling molecule, regulating gene expression in various organs and tissues. Its concentration in the blood may fluctuate in specific physiological and pathophysiological conditions. In this work, the regulation of the activity of organic cation transporters was measured by incubating human embryonic kidney cells stably expressing human OCT1 (hOCT1), hOCT2, or hMATE1 with high glucose concentrations (16.7 mM). Incubation with this high glucose concentration for 48 h significantly stimulated the activity of hOCT1, hOCT2, and hMATE1 by increasing their maximal velocity (Vmax), but without significantly changing their affinity for the substrates. These effects were independent of changes in osmolarity, as the addition of equimolar concentrations of mannitol did not alter transporter activity. The stimulation of transporter activity was associated with a significant increase in transporter mRNA expression. Inhibition of the mechanistic target of rapamycin (mTOR) kinase with Torin-1 suppressed the transporter stimulation induced by incubation with 16.7 mM glucose. Focusing on hOCT2, it was shown that incubation with 16.7 mM glucose increased hOCT2 protein expression in the plasma membrane. Interestingly, an apparent trend towards higher hOCT2 mRNA expression was observed in kidneys from diabetic patients, a pathology characterized by high serum glucose levels. Due to the small number of samples from diabetic patients (three), this observation must be interpreted with caution. In conclusion, incubation for 48 h with a high glucose concentration of 16.7 mM stimulated the activity and expression of organic cation transporters compared to those measured in the presence of 5.6 mM glucose. This stimulation by a diabetic environment could increase cellular uptake of the anti-diabetic drug metformin and increase renal tubular secretion of organic cations in an early stage of diabetes.
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- 2023
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9. Influence of physical activity on periodontal health in patients with type 2 diabetes mellitus. A blinded, randomized, controlled trial
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Wernicke, K., Grischke, J., Stiesch, M., Zeissler, S., Krüger, K., Bauer, P., Hillebrecht, A., and Eberhard, J.
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- 2021
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10. Report from the CVOT Summit 2020: new cardiovascular and renal outcomes
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Oliver Schnell, Xavier Cos, Francesco Cosentino, Thomas Forst, Francesco Giorgino, Hiddo J. L. Heersprink, Mikhail Kosiborod, Christoph Wanner, and Eberhard Standl
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Diabetes ,Cardiovascular disease ,Heart failure ,Chronic kidney disease ,Obesity ,VERTIS-CV ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 6th Cardiovascular Outcome Trial (CVOT) Summit “Cardiovascular and Renal Outcomes 2020” was the first to be held virtually on October 29–30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed. The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18–19, 2021 ( http://www.cvot.org ).
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- 2021
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11. Association Between Corneal Changes and Retinal Oximetry in Diabetes Mellitus.
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Ramm, Lisa, Spoerl, Eberhard, Terai, Naim, Herber, Robert, and Pillunat, Lutz E
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CORNEA , *DIABETES , *OXIMETRY , *DIABETIC retinopathy , *OXYGEN saturation , *RETINAL blood vessels - Abstract
aim Terai, Robert Herber, Lutz E Pillunat Department of Ophthalmology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, 01307, Germany Correspondence: Lisa Ramm, Department of Ophthalmology, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr 74, Dresden, 01307, Germany, Tel +49 351 458 3381, Fax +49 351 458 4335, Email [email protected] Purpose: Diabetes mellitus (DM) causes different corneal changes that are associated with the severity of diabetic retinopathy. To identify the pathophysiological reasons for this, corneal tomography and optical densitometry (COD) were combined with retinal oximetry. Methods: Patients with DM and healthy subjects were included in this pilot study. Spatially resolved corneal thickness and COD were assessed using the Pentacam HR (Oculus). The pachymetry difference (PACDiff) was calculated as an indicator of an increase in the peripheral corneal thickness. Oxygen saturation (SO2) of the retinal vessels was measured using the Retinal Vessel Analyzer (Imedos Systems UG). Subsequently, the associations between corneal and retinal parameters were analyzed. Results: Data from 30 patients with DM were compared with those from 30 age-matched healthy subjects. In DM, arterial (P = 0.048) and venous (P < 0.001) SO2 levels were increased, and arteriovenous SO2 difference was decreased (P < 0.001). In patients, PACDiff was higher than that in healthy subjects (P < 0.05), indicating a stronger increase in peripheral corneal thickness. The COD was reduced in DM (P = 0.004). The PACDiff of concentric rings with a diameter of 4 mm (r = − 0.404; P = 0.033) to 8 mm (r = − 0.522; P = 0.004) was inversely correlated with the arteriovenous SO2 difference. Furthermore, PACDiff 4 mm was negatively associated with arterial SO2 (r = − 0.389; P = 0.041), and the COD of the peripheral corneal areas correlated positive with arterial SO2 (COD total 10– 12 mm: r = 0.408; P = 0.025). Conclusion: These associations might indicate a common pathogenesis of corneal and retinal changes in DM, which could be caused by reduced oxygen supply, mitochondrial dysfunction, oxidative stress, and cytokine effects. Plain Language Summary: Retinal changes are particularly important for ophthalmologists in the management of diabetes mellitus. These are primarily consequences of diabetic vascular changes that can lead to a lack of oxygen. However, there is also evidence of significant changes in the cornea of patients with diabetes. In the present study, the associations between changes in corneal thickness profile, optical density of the cornea, and oxygen saturation of retinal vessels in diabetes mellitus were demonstrated for the first time. Therefore, this study could contribute to clarifying the possible causes of corneal changes in patients with diabetes. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Report from the 5th cardiovascular outcome trial (CVOT) summit
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Oliver Schnell, Eberhard Standl, Xavier Cos, Hiddo JL Heerspink, Baruch Itzhak, Nebojsa Lalic, Michael Nauck, and Antonio Ceriello
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Cardiovascular risk ,Diabetes ,CVOT ,CAROLINA ,CREDENCE ,DAPA-HF ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 5th Cardiovascular Outcome Trial (CVOT) Summit was held in Munich on October 24th–25th, 2019. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CAROLINA, CREDENCE, DAPA-HF, REWIND, and PIONEER-6. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for the treatment and prevention of heart failure and diabetic kidney disease in populations with and without diabetes, particularly using SGLT-2 inhibitors and GLP-1 receptor agonists. Furthermore, the ever increasing impact of CVOTs and substances tested for primary prevention and primary care was discussed. The 6th Cardiovascular Outcome Trial Summit will be held in Munich on October 29th–30th, 2020 ( https://www.cvot.org ).
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- 2020
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13. Report from the CVOT Summit 2020: new cardiovascular and renal outcomes
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Schnell, Oliver, Cos, Xavier, Cosentino, Francesco, Forst, Thomas, Giorgino, Francesco, Heersprink, Hiddo J. L., Kosiborod, Mikhail, Wanner, Christoph, and Standl, Eberhard
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- 2021
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14. The N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan Improves Glucose Homeostasis and Preserves Pancreatic Islets in NOD Mice.
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Wörmeyer, Laura, Nortmann, Oliver, Hamacher, Anna, Uhlemeyer, Celina, Belgardt, Bengt, Eberhard, Daniel, Mayatepek, Ertan, Meissner, Thomas, Lammert, Eckhard, and Welters, Alena
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ISLANDS of Langerhans ,METHYL aspartate receptors ,TYPE 1 diabetes ,TYPE 2 diabetes ,DEXTROMETHORPHAN - Abstract
For treatment of type 1 diabetes mellitus, a combination of immune-based interventions and medication to promote beta-cell survival and proliferation has been proposed. Dextromethorphan (DXM) is an N -methyl-D-aspartate receptor antagonist with a good safety profile, and to date, preclinical and clinical evidence for blood glucose-lowering and islet-cell-protective effects of DXM have only been provided for animals and individuals with type 2 diabetes mellitus. Here, we assessed the potential anti-diabetic effects of DXM in the non-obese diabetic mouse model of type 1 diabetes. More specifically, we showed that DXM treatment led to five-fold higher numbers of pancreatic islets and more than two-fold larger alpha- and beta-cell areas compared to untreated mice. Further, DXM treatment improved glucose homeostasis and reduced diabetes incidence by 50%. Our data highlight DXM as a novel candidate for adjunct treatment of preclinical or recent-onset type 1 diabetes. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group
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Oliver Schnell, Eberhard Standl, Doina Catrinoiu, Baruch Itzhak, Nebojsa Lalic, Dario Rahelic, Jan Skrha, Paul Valensi, and Antonio Ceriello
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Cardiovascular risk ,Diabetes ,CVOT ,CARMELINA ,DECLARE-TIMI 58 ,Harmony Outcomes ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held in Munich on 25–26 October 2018. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CARMELINA, DECLARE-TIMI 58 and Harmony Outcomes. Trial implications for diabetes management and the impact of the new ADA/EASD consensus statement treatment algorithm were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for adjunct therapy of type 1 diabetes and, on the occasion of the 10 year anniversary of the FDA’s “Guidance for Industry: “should CVOTs be continued and/or modified?” The 5th Cardiovascular Outcome Trial Summit will be held in Munich on 24–25 October 2019 (http://www.cvot.org).
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- 2019
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16. Comparison of mechanisms and transferability of outcomes of SGLT2 inhibition between type 1 and type 2 diabetes
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Oliver Schnell, Paul Valensi, Eberhard Standl, and Antonio Ceriello
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Diabetes ,mechanisms of SGLT‐2 inhibition ,SGLT‐2 inhibitor ,transferability ,type 2 diabetes ,type 1 diabetes ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Abstract Diabetes mellitus (DM) is a major chronic disease with ever‐increasing prevalence and a variety of serious complications for persons with DM, such as cardiovascular and/or renal complications. New glucose‐lowering therapies like DPP‐4 inhibitors, GLP‐1 receptor agonists, and SGLT‐2 inhibitors have undergone cardiovascular outcome trials (CVOTs) for type 2 diabetes (T2DM), as by the guidance of the FDA. However, CVOTs for type 1 diabetes (T1DM) are generally lacking. Both, persons with T1DM and T2DM, are burdened with a high incidence of cardiovascular and renal disease such as atherosclerotic cardiovascular disease (ASCVD) and diabetic kidney disease (DKD). Although pathologies of the two types of diabetes cannot be compared, similar mechanisms and risk factors like sex, hyperglycaemia, hypertension, endothelial damage and (background) inflammation have been identified in the development of CVD and DKD in T1DM and T2DM. Recent CVOTs in T2DM demonstrated that SGLT‐2 inhibitors, besides exerting a glucose‐lowering effect, have beneficial effects on cardiovascular and renal mechanisms. These mechanisms are reviewed in detail in this manuscript and evaluated for possible transferability to, and thus efficacy in, T1DM. Our review of current literature suggests that SGLT‐2 inhibitors have cardioprotective benefits beyond their glucose‐lowering effects. As this mainly has been observed in CVOTs in T2DM, further investigation in the adjunctive therapy for type 1 diabetes is suggested.
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- 2020
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17. Report from the 3rd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group
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Oliver Schnell, Eberhard Standl, Doina Catrinoiu, Stefano Genovese, Nebojsa Lalic, Katarina Lalic, Jan Skrha, Paul Valensi, and Antonio Ceriello
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CVOT Summit ,D&CVD EASD Study Group ,Diabetes ,Cardiovascular risk ,CVOT ,DEVOTE ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract The 3rd Cardiovascular Outcome Trial Summit of the Diabetes & Cardiovascular Disease EASD Study Group was held on the 26–27 October 2017 in Munich. As in 2015 and 2016, this summit was organised in light of recently completed and published CVOTs on diabetes, aiming to serve as a reference meeting for in-depth discussions on the topic. Amongst others, the CVOTs EXSCEL, DEVOTE, the CANVAS program and the ACE-trial, which released primary outcome results in 2017, were discussed. Trial implications for diabetes management and recent perspectives of diabetologists, cardiologists, endocrinologists, nephrologists and general practitioners were highlighted. The clinical relevance of cardiovascular outcome trials and its implications regarding reimbursement were compared with real-world studies. The 4th Cardiovascular Outcome Trial Summit will be held in Munich 25–26 October 2018 (http://www.dcvd.org).
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- 2018
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18. Report from the 5th cardiovascular outcome trial (CVOT) summit
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Schnell, Oliver, Standl, Eberhard, Cos, Xavier, Heerspink, Hiddo JL, Itzhak, Baruch, Lalic, Nebojsa, Nauck, Michael, and Ceriello, Antonio
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- 2020
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19. Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by Biallelic DNAJC3 Variants.
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Welters, Alena, Nortmann, Oliver, Wörmeyer, Laura, Freiberg, Clemens, Eberhard, Daniel, Bachmann, Nadine, Bergmann, Carsten, Mayatepek, Ertan, Meissner, Thomas, and Kummer, Sebastian
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HYPERINSULINISM ,MICE ,INSULIN ,INTRACELLULAR calcium ,HYPOGLYCEMIA ,DIABETES ,ADOLESCENCE ,HOMEOSTASIS - Abstract
The BiP co-chaperone DNAJC3 protects cells during ER stress. In mice, the deficiency of DNAJC3 leads to beta-cell apoptosis and the gradual onset of hyperglycemia. In humans, biallelic DNAJC3 variants cause a multisystem disease, including early-onset diabetes mellitus. Recently, hyperinsulinemic hypoglycemia (HH) has been recognized as part of this syndrome. This report presents a case study of an individual with HH caused by DNAJC3 variants and provides an overview of the metabolic phenotype of individuals with HH and DNAJC3 variants. The study demonstrates that HH may be a primary symptom of DNAJC3 deficiency and can persist until adolescence. Additionally, glycemia and insulin release were analyzed in young DNACJ3 knockout (K.O.) mice, which are equivalent to human infants. In the youngest experimentally accessible age group of 4-week-old mice, the in vivo glycemic phenotype was already dominated by a reduced total insulin secretion capacity. However, on a cellular level, the degree of insulin release of DNAJC3 K.O. islets was higher during periods of increased synthetic activity (high-glucose stimulation). We propose that calcium leakage from the ER into the cytosol, due to disrupted DNAJC3-controlled gating of the Sec61 channel, is the most likely mechanism for HH. This is the first genetic mechanism explaining HH solely by the disruption of intracellular calcium homeostasis. Clinicians should screen for HH in DNAJC3 deficiency and consider DNAJC3 variants in the differential diagnosis of congenital hyperinsulinism. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Updates on cardiovascular outcome trials in diabetes
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Oliver Schnell, Lars Rydén, Eberhard Standl, Antonio Ceriello, and on behalf of the D&CVD EASD Study Group
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Cardiovascular risk ,Diabetes ,CVOT ,DEVOTE ,CANVAS program ,EXSCEL ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk. The present review summarizes the results of the DEVOTE, CANVAS, EXSCEL and ACE trials that tested cardiovascular safety of Insulin degludec, canagliflozin, once-weekly exenatide and acarbose and were published in 2017. We provide context on these results by comparing them with earlier trials of glucose-lowering drugs and give an outlook on what to expect in coming years.
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- 2017
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21. The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats
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Sebastian Steven, Matthias Oelze, Alina Hanf, Swenja Kröller-Schön, Fatemeh Kashani, Siyer Roohani, Philipp Welschof, Maximilian Kopp, Ute Gödtel-Armbrust, Ning Xia, Huige Li, Eberhard Schulz, Karl J. Lackner, Leszek Wojnowski, Serge P. Bottari, Philip Wenzel, Eric Mayoux, Thomas Münzel, and Andreas Daiber
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SGLT2 inhibitor ,Zucker diabetic fatty rats ,Diabetes ,Oxidative stress ,Endothelial dysfunction ,Low-grade inflammation ,AGE/RAGE signaling ,β-cell content ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male ZDF rats were used as a model of T2DM (35 diabetic ZDF‐Leprfa/fa and 16 ZDF-Lepr+/+ controls). Empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 6 weeks. Treatment with empagliflozin restored glycemic control. Empagliflozin improved endothelial function (thoracic aorta) and reduced oxidative stress in the aorta and in blood of diabetic rats. Inflammation and glucotoxicity (AGE/RAGE signaling) were epigenetically prevented by SGLT2i treatment (ChIP). Linear regression analysis revealed a significant inverse correlation of endothelial function with HbA1c, whereas leukocyte-dependent oxidative burst and C-reactive protein (CRP) were positively correlated with HbA1c. Viability of hyperglycemic endothelial cells was pleiotropically improved by SGLT2i. Empagliflozin reduces glucotoxicity and thereby prevents the development of endothelial dysfunction, reduces oxidative stress and exhibits anti-inflammatory effects in ZDF rats, despite persisting hyperlipidemia and hyperinsulinemia. Our preclinical observations provide insights into the mechanisms by which empagliflozin reduces cardiovascular mortality in humans (EMPA-REG trial).
- Published
- 2017
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22. Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group
- Author
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Schnell, Oliver, Standl, Eberhard, Catrinoiu, Doina, Itzhak, Baruch, Lalic, Nebojsa, Rahelic, Dario, Skrha, Jan, Valensi, Paul, and Ceriello, Antonio
- Published
- 2019
- Full Text
- View/download PDF
23. Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.
- Author
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Ceriello, Antonio, Rodbard, Helena W., Battelino, Tadej, Brosius, Frank, Cosentino, Francesco, Green, Jennifer, Ji, Linong, Kellerer, Monika, Koob, Susan, Kosiborod, Mikhail, Lalic, Nebojsa, Marx, Nikolaus, Nedungadi, T. Prashant, Parkin, Christopher G., Rydén, Lars, Sheu, Wayne Huey-Herng, Standl, Eberhard, Vandvik, Per Olav, and Schnell, Oliver
- Subjects
TYPE 2 diabetes ,MINERALOCORTICOID receptors ,GLUCAGON-like peptide-1 receptor ,DIABETES ,GLUCAGON-like peptide-1 agonists ,HYPERGLYCEMIA - Abstract
In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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24. Regulation of Transporters for Organic Cations by High Glucose.
- Author
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Steinbüchel, Martin, Menne, Johannes, Schröter, Rita, Neugebauer, Ute, Schlatter, Eberhard, and Ciarimboli, Giuliano
- Subjects
ORGANIC cation transporters ,METFORMIN ,REMOTE sensing ,GLUCOSE ,PROTEIN transport ,CARRIER proteins ,BLOOD proteins - Abstract
Endogenous positively charged organic substances, including neurotransmitters and cationic uremic toxins, as well as exogenous organic cations such as the anti-diabetic medication metformin, serve as substrates for organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs). These proteins facilitate their transport across cell membranes. Vectorial transport through the OCT/MATE axis mediates the hepatic and renal excretion of organic cations, regulating their systemic and local concentrations. Organic cation transporters are part of the remote sensing and signaling system, whose activity can be regulated to cope with changes in the composition of extra- and intracellular fluids. Glucose, as a source of energy, can also function as a crucial signaling molecule, regulating gene expression in various organs and tissues. Its concentration in the blood may fluctuate in specific physiological and pathophysiological conditions. In this work, the regulation of the activity of organic cation transporters was measured by incubating human embryonic kidney cells stably expressing human OCT1 (hOCT1), hOCT2, or hMATE1 with high glucose concentrations (16.7 mM). Incubation with this high glucose concentration for 48 h significantly stimulated the activity of hOCT1, hOCT2, and hMATE1 by increasing their maximal velocity (V
max ), but without significantly changing their affinity for the substrates. These effects were independent of changes in osmolarity, as the addition of equimolar concentrations of mannitol did not alter transporter activity. The stimulation of transporter activity was associated with a significant increase in transporter mRNA expression. Inhibition of the mechanistic target of rapamycin (mTOR) kinase with Torin-1 suppressed the transporter stimulation induced by incubation with 16.7 mM glucose. Focusing on hOCT2, it was shown that incubation with 16.7 mM glucose increased hOCT2 protein expression in the plasma membrane. Interestingly, an apparent trend towards higher hOCT2 mRNA expression was observed in kidneys from diabetic patients, a pathology characterized by high serum glucose levels. Due to the small number of samples from diabetic patients (three), this observation must be interpreted with caution. In conclusion, incubation for 48 h with a high glucose concentration of 16.7 mM stimulated the activity and expression of organic cation transporters compared to those measured in the presence of 5.6 mM glucose. This stimulation by a diabetic environment could increase cellular uptake of the anti-diabetic drug metformin and increase renal tubular secretion of organic cations in an early stage of diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2023
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25. CVOT Summit 2022 Report:new cardiovascular, kidney, and glycemic outcomes
- Author
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Schnell, Oliver, Battelino, Tadej, Bergenstal, Richard, Birkenfeld, Andreas L., Ceriello, Antonio, Cheng, Alice, Davies, Melanie, Edelman, Steve, Forst, Thomas, Giorgino, Francesco, Green, Jennifer, Groop, Per Henrik, Hadjadj, Samy, J.L.Heerspink, Hiddo, Hompesch, Marcus, Izthak, Baruch, Ji, Linong, Kanumilli, Naresh, Mankovsky, Boris, Mathieu, Chantal, Miszon, Martin, Mustafa, Reem, Nauck, Michael, Pecoits-Filho, Roberto, Pettus, Jeremy, Ranta, Kari, Rodbard, Helena W., Rossing, Peter, Ryden, Lars, Schumm-Draeger, Petra Maria, Solomon, Scott D., Škrha, Jan, Topsever, Pinar, Vilsbøll, Tina, Wilding, John, Standl, Eberhard, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
- Subjects
Endocrinology, Diabetes and Metabolism ,Chronic kidney disease ,Diabetes ,Heart failure ,SGLT2 inhibitor ,Obesity ,Cardiology and Cardiovascular Medicine ,Cardiovascular disease ,GIP/GLP-1 receptor agonist - Abstract
The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10–12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year’s focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23–24, 2023 (http://www.cvot.org).
- Published
- 2023
26. Report from the 3rd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group
- Author
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Schnell, Oliver, Standl, Eberhard, Catrinoiu, Doina, Genovese, Stefano, Lalic, Nebojsa, Lalic, Katarina, Skrha, Jan, Valensi, Paul, and Ceriello, Antonio
- Published
- 2018
- Full Text
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27. Issues for the management of people with diabetes and COVID-19 in ICU
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Antonio Ceriello, Paul Valensi, Jan Škrha, Baruch Itzhak, Dario Rahelić, Eberhard Standl, Nebojsa Lalic, Oliver Schnell, and Doina Catrinoiu
- Subjects
Blood Glucose ,Diabetes, Intensive Care Unit ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Coronavirus disease 2019 (COVID-19) ,Endocrinology, Diabetes and Metabolism ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Review ,Hypoglycemia ,Risk Assessment ,law.invention ,Betacoronavirus ,law ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Pandemic ,medicine ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,Cardiovascular complications ,Intensive care medicine ,Pandemics ,Antihypertensive Agents ,Glycemic ,Dyslipidemias ,business.industry ,SARS-CoV-2 ,COVID-19 ,medicine.disease ,Intensive care unit ,Intensive Care Units ,Treatment Outcome ,lcsh:RC666-701 ,Diabetes ,Intensive Care Unit ,Host-Pathogen Interactions ,Hypertension ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,Coronavirus Infections ,Biomarkers - Abstract
In the pandemic “Corona Virus Disease 2019” (COVID-19) people with diabetes have a high risk to require ICU admission. The management of diabetes in Intensive Care Unit is always challenging, however, when diabetes is present in COVID-19 the situation seems even more complicated. An optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. In this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by “Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells. A real issue is the usefulness of several biomarkers, which have been suggested to be measured during the COVID-19. N-Terminal-pro-Brain Natriuretic-Peptide, D-dimer and hs-Troponin are often increased in diabetes. Their meaning in the case of diabetes and COVID-19 should be therefore very carefully evaluated. Even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act.
- Published
- 2020
28. Report from the CVOT Summit 2021:new cardiovascular, renal, and glycemic outcomes
- Author
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Oliver Schnell, Tadej Battelino, Richard Bergenstal, Matthias Blüher, Michael Böhm, Frank Brosius, Richard D. Carr, Antonio Ceriello, Thomas Forst, Francesco Giorgino, Bruno Guerci, Hiddo J. L. Heerspink, Baruch Itzhak, Linong Ji, Mikhail Kosiborod, Nebojša Lalić, Michael Lehrke, Nikolaus Marx, Michael Nauck, Helena W. Rodbard, Giuseppe M. C. Rosano, Peter Rossing, Lars Rydén, Francesca Santilli, Petra-Maria Schumm-Draeger, Per Olav Vandvik, Tina Vilsbøll, Christoph Wanner, Carol Wysham, Eberhard Standl, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
- Subjects
Blood Glucose ,Clinical Trials as Topic ,GLP-1 receptor agonist ,Mineralocorticoid receptor antagonist ,Endocrinology, Diabetes and Metabolism ,Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ,education ,Diabetes ,COVID-19 ,Heart failure ,SGLT2 inhibitor ,7. Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, online, 2021-11-18 - 2021-11-19 ,Hypoglycemic Agents/therapeutic use ,Cardiovascular disease ,Tirzepatide ,Diabetes Mellitus/drug therapy ,Living guidelines ,Treatment Outcome ,Chronic kidney disease ,Humans ,Obesity ,Cardiovascular Diseases/drug therapy ,Cardiology and Cardiovascular Medicine - Abstract
Cardiovascular diabetology 21, 50 (2022). doi:10.1186/s12933-022-01481-0, Published by BioMed Central, London
- Published
- 2022
29. Report from the CVOT Summit 2020
- Author
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Thomas Forst, Christoph Wanner, Oliver Schnell, Xavier Cos, Eberhard Standl, Francesco Cosentino, Francesco Giorgino, Hiddo J. L. Heersprink, Mikhail Kosiborod, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
- Subjects
Research Report ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Coronavirus disease 2019 (COVID-19) ,GLP-1 receptor agonist ,Endocrinology, Diabetes and Metabolism ,Heart failure ,Kidney ,Diabetes management ,Internal medicine ,Diabetes mellitus ,Chronic kidney disease ,Epidemiology ,medicine ,Humans ,Obesity ,Renal Insufficiency, Chronic ,SGLT2i inhibitor ,Intensive care medicine ,Sodium-Glucose Transporter 2 Inhibitors ,Mineralocorticoid Receptor Antagonists ,VERTIS-CV ,geography ,Clinical Trials as Topic ,Summit ,geography.geographical_feature_category ,business.industry ,Mineralocorticoid receptor antagonist ,DAPA-CKD ,Diabetes ,COVID-19 ,Congresses as Topic ,medicine.disease ,Cardiovascular disease ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,lcsh:RC666-701 ,Cardiovascular Diseases ,Commentary ,EMPEROR-Reduced ,Cardiology and Cardiovascular Medicine ,business ,FIDELIO-DKD ,Kidney disease - Abstract
The 6th Cardiovascular Outcome Trial (CVOT) Summit “Cardiovascular and Renal Outcomes 2020” was the first to be held virtually on October 29–30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed.The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18–19, 2021 (http://www.cvot.org).
- Published
- 2021
30. Hypoglycaemia and its management in primary care setting
- Author
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Jaakko Tuomilehto, Eytan Roitman, Peter Gæde, Amy Hess Fischl, Guillermo E. Umpierrez, Mahmoud Ibrahim, Sandra L. Weber, Paolo Pozzilli, Jason Baker, R. David Leslie, Robert H. Eckel, Avivit Cahn, Bjørn Richelsen, Eberhard Standl, Yoel Toledano, Silvia Pieralice, Nuha El Sayed, and Dario Tuccinardi
- Subjects
medicine.medical_specialty ,COGNITIVE DYSFUNCTION ,diabetes self-management education ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Disease ,Type 2 diabetes ,DEPENDENT DIABETES-MELLITUS ,030204 cardiovascular system & hematology ,Hypoglycemia ,hypoglycaemia unawareness pregnancy ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Quality of life ,Diabetes mellitus ,GLYCEMIC CONTROL ,Internal Medicine ,Medicine ,Humans ,Hypoglycemic Agents ,Intensive care medicine ,Type 1 diabetes ,Primary Health Care ,diabetes ,business.industry ,Insulin ,REAL-TIME ,GLUCOSE-SENSING TECHNOLOGY ,AUTONOMIC FAILURE ,INTENSIVE INSULIN THERAPY ,Disease Management ,nutritional and metabolic diseases ,medicine.disease ,OPEN-LABEL ,IMPAIRED AWARENESS ,3. Good health ,Clinical trial ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,technology ,continuous glucose monitoring ,business ,PREGNANT-WOMEN ,hormones, hormone substitutes, and hormone antagonists ,hypoglycaemia - Abstract
Hypoglycaemia is common in patients with type 1 diabetes and type 2 diabetes and constitutes a major limiting factor in achieving glycaemic control among people with diabetes. While hypoglycaemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycaemic control. Severe hypoglycaemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycaemia is the most important safety outcome in clinical studies of glucose lowering agents. The American Diabetes Association Standards of Medical Care recommends that a management protocol for hypoglycaemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycaemic events with the use of newer anti-diabetic drugs. Increased hypoglycaemia risk is observed with the use of insulin and/or sulphonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycaemia and cardiovascular outcomes show features of “frailty.” Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia and with history of severe hypoglycaemia. Patients with impaired awareness of hypoglycaemia benefit from real-time CGM. The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycaemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycaemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycaemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycaemia. Several therapeutic considerations are important to reduce hypoglycaemia risk during pregnancy including administration of rapid-acting insulin analogues rather than human insulin, pre-conception initiation of insulin analogues, and immediate postpartum insulin dose reduction.
- Published
- 2020
31. Hypoglycaemia and its management in primary care setting
- Author
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Ibrahim, Mahmoud, Baker, Jason, Cahn, Avivit, Eckel, Robert H., Sayed, Nuha Ali El, Fischl, Amy Hess, Gaede, Peter, Leslie, R. David, Pieralice, Silvia, Tuccinardi, Dario, Pozzilli, Paolo, Richelsen, Bjørn, Roitman, Eytan, Standl, Eberhard, Toledano, Yoel, Tuomilehto, Jaakko, Weber, Sandra L., Umpierrez, Guillermo E., and Clinicum
- Subjects
Continuous glucose monitoring (CGM) ,Technology ,COGNITIVE DYSFUNCTION ,diabetes self-management education ,endocrine system diseases ,diabetes ,REAL-TIME ,GLUCOSE-SENSING TECHNOLOGY ,AUTONOMIC FAILURE ,nutritional and metabolic diseases ,INTENSIVE INSULIN THERAPY ,DEPENDENT DIABETES-MELLITUS ,OPEN-LABEL ,IMPAIRED AWARENESS ,Hypoglycemia ,hypoglycaemia unawareness pregnancy ,3121 General medicine, internal medicine and other clinical medicine ,GLYCEMIC CONTROL ,continuous glucose monitoring ,hypoglycemia unawareness Pregnancy ,PREGNANT-WOMEN ,hypoglycaemia - Abstract
Hypoglycemia is common in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) and constitutes a major limiting factor in achieving glycemic control among people with diabetes. While hypoglycemia is defined as a blood glucose level under 70 mg/dL (3.9?mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycemic control. Severe hypoglycemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycemia is the most important safety outcome in clinical studies of glucose lowering agents. The ADA Standards of Medical Care recommends that a management protocol for hypoglycemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycemic events with the use of newer antidiabetic drugs. Increased hypoglycemia risk is observed with the use of insulin and/or sulfonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycemia and Cardiovascular (CV) outcomes show features of ?frailty?. Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. CGM should be considered for all individuals with increased risk for hypoglycemia, impaired hypoglycemia awareness, frequent nocturnal hypoglycemia and with history of severe hypoglycemia. Patients with impaired awareness of hypoglycemia (IAH) benefit from real-time continuous glucose monitoring (CGM). The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycemia. Several therapeutic considerations are important to reduce hypoglycemia risk during pregnancy including administration of rapid-acting insulin analogs rather than human insulin, pre-conception initiation of insulin analogs, and immediate postpartum insulin dose reduction. This article is protected by copyright. All rights reserved.
- Published
- 2020
32. Diabetes and cardiovascular disease: Current status of trials
- Author
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Schnell, Oliver and Standl, Eberhard
- Published
- 2010
- Full Text
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33. Are Inflamed Periodontal Tissues Endogenous Source of Advanced Glycation End-Products (AGEs) in Individuals with and without Diabetes Mellitus? A Systematic Review.
- Author
-
Chopra, Aditi, Jayasinghe, Thilini N., and Eberhard, Joerg
- Subjects
ADVANCED glycation end-products ,HYPERGLYCEMIA ,DIABETES ,GLYCEMIC index ,GLYCEMIC control - Abstract
Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs are associated with insulin resistance and poor glycemic control. Recently, inflamed periodontal tissues and certain oral bacteria were observed to increase the local and systemic AGE levels in both normoglycemic and hyperglycemic individuals. Although hyperglycemia induced AGE and its effect on the periodontal tissues is known, periodontitis as an endogenous source of AGE formation is not well explored. Hence, this systematic review is aimed to explore, for the first time, whether inflamed periodontal tissues and periodontal pathogens have the capacity to modulate AGE levels in individuals with or without T2DM and how this affects the glycemic load. Six electronic databases were searched using the following keywords: (Periodontitis OR Periodontal disease OR Periodontal Inflammation) AND (Diabetes mellitus OR Hyperglycemia OR Insulin resistance) AND Advanced glycation end products. The results yielded 1140 articles, of which 13 articles were included for the review. The results showed that the mean AGE levels in gingival crevicular fluid was higher in individuals with diabetes mellitus and periodontitis (521.9 pg/mL) compared to healthy individuals with periodontitis (234.84 pg/mL). The serum AGE levels in normoglycemic subjects having periodontitis was higher compared to those without periodontitis (15.91 ng/mL vs. 6.60 ng/mL). Tannerella forsythia, a common gram-negative anaerobe periodontal pathogen in the oral biofilm, was observed to produce methylglyoxal (precursor of AGE) in the gingival tissues. Increased AGE deposition and activate of AGE receptors was noted in the presence of periodontitis in both normoglycemic and hyperglycemic individuals. Hence, it can be concluded that periodontitis can modulate the local and systemic levels of AGE levels even in absence of hyperglycemia. This explains the bidirectional relationship between periodontitis and development of prediabetes, incident diabetes, poor glycemic control, and insulin resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
34. Diabetes as a cardiovascular risk factor : An overview of global trends of macro and micro vascular complications
- Author
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Antonio Ceriello, Joline W.J. Beulens, Marc Ferrini, Elisa Dal Canto, Tina Birgitte Hansen, Oliver Schnell, Lars Rydén, Eberhard Standl, Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, and ACS - Heart failure & arrhythmias
- Subjects
microvascular complications ,medicine.medical_specialty ,Epidemiology ,Population ,030209 endocrinology & metabolism ,Disease ,030204 cardiovascular system & hematology ,Overweight ,Global Health ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,macrovascular complications ,Risk Factors ,cardiovascular disease ,cardiovascular mortality ,Diabetes mellitus ,medicine ,Humans ,Risk factor ,Intensive care medicine ,education ,Cause of death ,education.field_of_study ,business.industry ,Mortality rate ,Diabetes ,Type 2 Diabetes Mellitus ,medicine.disease ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,medicine.symptom ,business ,Cardiology and Cardiovascular Medicine - Abstract
The global prevalence of diabetes is predicted to increase dramatically in the coming decades as the population grows and ages, in parallel with the rising burden of overweight and obesity, in both developed and developing countries. Cardiovascular disease represents the principal cause of death and morbidity among people with diabetes, especially in those with type 2 diabetes mellitus. Adults with diabetes have 2–4 times increased cardiovascular risk compared with adults without diabetes, and the risk rises with worsening glycaemic control. Diabetes has been associated with 75% increase in mortality rate in adults, and cardiovascular disease accounts for a large part of the excess mortality. Diabetes-related macrovascular and microvascular complications, including coronary heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, chronic renal disease, diabetic retinopathy and cardiovascular autonomic neuropathy are responsible for the impaired quality of life, disability and premature death associated with diabetes. Given the substantial clinical impact of diabetes as a cardiovascular risk factor, there has been a growing focus on diabetes-related complications. While some population-based studies suggest that the epidemiology of such complications is changing and that rates of all-cause and cardiovascular mortality among individuals with diabetes are decreasing in high-income countries, the economic and social burden of diabetes is expected to rise due to changing demographics and lifestyle especially in middle- and low-income countries. In this review we outline data from population-based studies on recent and long-term trends in diabetes-related complications.
- Published
- 2019
35. Oral health and cardiometabolic disease: understanding the relationship.
- Author
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King, Shalinie, Chow, Clara K., and Eberhard, Joerg
- Subjects
CARDIOVASCULAR diseases risk factors ,ORAL health ,PERIODONTITIS ,CARDIOVASCULAR diseases ,TYPE 2 diabetes ,XEROSTOMIA - Abstract
Examination of the oral cavity can identify clinical signs indicative of underlying systemic disease. Key features to examine include the general appearance and number of the teeth, signs of inflammation of the mucosa or gingival tissues including bleeding of the gums and redness, swelling or hyperplasia. Additionally, the tongue should be assessed for any ulceration or discolouration and the presence of excessive build‐up (coating). Cardiovascular disease and diabetes, together known as cardiometabolic disease have an impact on oral health. Similarly, oral health conditions, such as gum disease (periodontitis) and dryness of the mouth (xerostomia), are associated with an increased risk for both cardiovascular disease and type 2 diabetes mellitus. The aim of this narrative review is to outline both the impact of periodontitis and xerostomia on cardiometabolic disease and the impact of cardiometabolic health on these oral health conditions. Key features of periodontitis and xerostomia will be provided along with a brief discussion of current concepts in early prevention and management of these oral health conditions. The biological mechanisms linking cardiometabolic disease and periodontitis will be outlined and the evidence supporting the association between cardiometabolic disease and oral health conditions will be presented together with an identification of areas where further research is indicated. Last, guidance for general practitioners to assess and support early diagnosis and management of oral health conditions by raising awareness of the relationship between oral health and cardiometabolic disease, providing simple oral health advice and referring to a dental practitioner will be presented. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
36. Is the Corneal Thickness Profile Altered in Diabetes Mellitus?
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Ramm, Lisa, Spoerl, Eberhard, Pillunat, Lutz E., and Terai, Naim
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- *
DIABETES , *INTRAOCULAR pressure , *DIABETIC retinopathy , *DISEASE duration , *PEOPLE with diabetes - Abstract
Purpose: To investigate the influence of chronic hyperglycemia in diabetes mellitus (DM) on spatial corneal thickness distribution and to analyze the influence of disease-specific factors. Methods: DM patients and healthy subjects were matched according to age and intraocular pressure (IOP). In diabetics, disease duration, DM type, and HbA1c value were assessed. Spatially resolved corneal thickness was measured by Pentacam HR. Thinnest corneal thickness (TCT) and peripheral pachymetry of concentric circles around TCT were determined. The Dynamic Scheimpflug Analyzer Corvis ST (CST) was used to measure the parameter pachy slope, which is an indicator of the change of corneal thickness from the apex to the periphery. Results: 59 DM patients and 57 healthy subjects were included. Age (P =.486) and IOP (P =.154) were not different between the groups. In DM, pachy slope was significantly higher than in healthy subjects (41.1 ± 9.87 vs. 35.18 ± 10.64 μm, P =.004). Also, the differences between TCT and the average of peripheral corneal thickness of concentric circles with a diameter of 2 mm (10.3 ± 1.7 vs. 9.3 ± 3.8 μm, P <.001) to 6 mm (82.2 ± 12.4 vs. 76.8 ± 12.6 μm, P =.011) were increased in patients. Changes in thickness profile were associated with HbA1c value and presence of diabetic retinopathy or maculopathy. Conclusion: In DM, a stronger peripheral corneal thickness increase was detectable. This change was shown using the novel CST parameter pachy slope and confirmed by Pentacam readings. These alterations might affect IOP and biomechanical measurements, and influence refractive procedures. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
37. Comparison of mechanisms and transferability of outcomes of SGLT2 inhibition between type 1 and type 2 diabetes.
- Author
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Schnell, Oliver, Valensi, Paul, Standl, Eberhard, and Ceriello, Antonio
- Subjects
TYPE 1 diabetes ,GLUCOSE - Abstract
Diabetes mellitus (DM) is a major chronic disease with ever‐increasing prevalence and a variety of serious complications for persons with DM, such as cardiovascular and/or renal complications. New glucose‐lowering therapies like DPP‐4 inhibitors, GLP‐1 receptor agonists, and SGLT‐2 inhibitors have undergone cardiovascular outcome trials (CVOTs) for type 2 diabetes (T2DM), as by the guidance of the FDA. However, CVOTs for type 1 diabetes (T1DM) are generally lacking. Both, persons with T1DM and T2DM, are burdened with a high incidence of cardiovascular and renal disease such as atherosclerotic cardiovascular disease (ASCVD) and diabetic kidney disease (DKD). Although pathologies of the two types of diabetes cannot be compared, similar mechanisms and risk factors like sex, hyperglycaemia, hypertension, endothelial damage and (background) inflammation have been identified in the development of CVD and DKD in T1DM and T2DM. Recent CVOTs in T2DM demonstrated that SGLT‐2 inhibitors, besides exerting a glucose‐lowering effect, have beneficial effects on cardiovascular and renal mechanisms. These mechanisms are reviewed in detail in this manuscript and evaluated for possible transferability to, and thus efficacy in, T1DM. Our review of current literature suggests that SGLT‐2 inhibitors have cardioprotective benefits beyond their glucose‐lowering effects. As this mainly has been observed in CVOTs in T2DM, further investigation in the adjunctive therapy for type 1 diabetes is suggested. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
38. A review of the hours dedicated to oral health education in medical programmes across Australia.
- Author
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Abbott, Bronwyn, Zybutz, Cian, Scott, Karen M., Eberhard, Joerg, and Widmer, Richard
- Subjects
CHRONIC disease diagnosis ,CHRONIC disease treatment ,WOUND care ,MOUTH anatomy ,ANATOMY ,DENTAL caries ,DENTAL health education ,DIABETES ,EXECUTIVES ,RESEARCH methodology ,MEDICAL schools ,MEDICAL students ,MOUTH tumors ,PATIENT education ,PERIODONTAL disease ,QUESTIONNAIRES ,SURVEYS ,TEACHING ,TIME ,UNIVERSITIES & colleges ,DISEASE management ,HEALTH literacy ,EARLY diagnosis ,EVALUATION of human services programs - Abstract
Abstract: Background: Oral health is an important predictor for general health, and poor oral health is interrelated with the manifestations of systemic disease. Aim: To determine the extent of oral health education in medical schools across Australia. Methods: A survey of Australian medical schools was conducted (September 2013 to June 2014). Participants were administrators and curricula coordinators of medical programmes. The main outcome measures were teaching hours of specific areas of oral health education. Data were descriptively analysed. Results: Participants from 8 of 18 universities responded to the questionnaire. The total hours dedicated to oral health in the medical programmes were: zero in one school; less than 2 h in three schools, 6–10 h in three schools and 30 h in one school. Only four schools taught the correlation between oral health and overall health, two schools taught about dental diseases (caries and periodontal disease), three schools taught dental trauma management and six schools taught oral anatomy. Only five schools taught about oral cancer: two of these taught about cancer for 10–15 min. No school reported hands‐on training in an oral health setting. Conclusions: The results indicate that Australian medical school graduates have little, if any, foundational knowledge of oral health (dental caries, bidirectional relationship between diabetes and periodontal disease, oral cancer and dental emergencies). The recognition of poor oral health plays a significant part in the early detection and care of chronic diseases. The teaching of fundamental oral health to medical students is crucial and should be integrated into medical school curricula. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
39. Pancreatic islet protection at the expense of secretory function involves serine-linked mitochondrial one-carbon metabolism.
- Author
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Pelligra, Angela, Mrugala, Jessica, Griess, Kerstin, Kirschner, Philip, Nortmann, Oliver, Bartosinska, Barbara, Köster, Andrea, Krupenko, Natalia I., Gebel, Dominik, Westhoff, Philipp, Steckel, Bodo, Eberhard, Daniel, Herebian, Diran, Belgardt, Bengt-Frederik, Schrader, Jürgen, Weber, Andreas P.M., Krupenko, Sergey A., and Lammert, Eckhard
- Abstract
Type 2 diabetes is characterized by insulin hypersecretion followed by reduced glucose-stimulated insulin secretion (GSIS). Here we show that acute stimulation of pancreatic islets with the insulin secretagogue dextrorphan (DXO) or glibenclamide enhances GSIS, whereas chronic treatment with high concentrations of these drugs reduce GSIS but protect islets from cell death. Bulk RNA sequencing of islets shows increased expression of genes for serine-linked mitochondrial one-carbon metabolism (OCM) after chronic, but not acute, stimulation. In chronically stimulated islets, more glucose is metabolized to serine than to citrate, and the mitochondrial ATP/ADP ratio decreases, whereas the NADPH/NADP
+ ratio increases. Activating transcription factor-4 (Atf4) is required and sufficient to activate serine-linked mitochondrial OCM genes in islets, with gain- and loss-of-function experiments showing that Atf4 reduces GSIS and is required, but not sufficient, for full DXO-mediated islet protection. In sum, we identify a reversible metabolic pathway that provides islet protection at the expense of secretory function. [Display omitted] • Chronic insulin secretagogues increase islet viability but decrease secretory function • Insulin secretagogues can enhance serine-linked mitochondrial one-carbon metabolism • High-dose K ATP -dependent insulin secretagogue DXO can deviate glucose flux to serine • Phgdh , Mthfd2 , and Shmt2 limit insulin secretion but promote islet cell viability Pelligra et al. find that chronic exposure to high doses of K ATP -dependent insulin secretagogues protects islets from cell death at the expense of secretory function. Dysfunctional islets upregulate serine-linked OCM genes and glucose flux to serine. Simultaneous knockdown of serine-linked mitochondrial OCM genes enhances insulin secretion but decreases islet viability. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
40. Updates on cardiovascular outcome trials in diabetes.
- Author
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Schnell, Oliver, Rydén, Lars, Standl, Eberhard, and Ceriello, Antonio
- Subjects
DIABETES complications ,CARDIOVASCULAR disease etiology ,HYPERGLYCEMIA ,ENZYME inhibitors ,CLINICAL trials - Abstract
In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk. The present review summarizes the results of the DEVOTE, CANVAS, EXSCEL and ACE trials that tested cardiovascular safety of Insulin degludec, canagliflozin, once-weekly exenatide and acarbose and were published in 2017. We provide context on these results by comparing them with earlier trials of glucose-lowering drugs and give an outlook on what to expect in coming years. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
41. Report from the 2nd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group.
- Author
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Schnell, Oliver, Standl, Eberhard, Catrinoiu, Doina, Genovese, Stefano, Lalic, Nebojsa, Skra, Jan, Valensi, Paul, Raheli, Dario, and Ceriello, Antonio
- Subjects
- *
CARDIOVASCULAR diseases , *DIABETES , *CARDIOLOGISTS , *NEPHROLOGISTS , *CARDIOLOGY - Abstract
The 2nd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group was held on the 20th-21st October 2016 in Munich. This second Summit was organized in light of recently published CVOTs on diabetes, with the aim of serving as a reference meeting for discussion on this topic. Along with presentations on the results of the most recently published CVOTs, panel discussions on trial implications for reimbursement and the perspective of cardiologists and/or nephrologists, as well as on CVOTs weaknesses and potentials constituted the heart of the program. Future activities of the D&CVD EASD Study Group in 2017 include an annual meeting in Milano and the 3rd CVOT Summit on Diabetes of the D&CVD EASD Study Group, in Munich (http:// www.dcvd.org). [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
42. Current perspectives on cardiovascular outcome trials in diabetes.
- Author
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Schnell, Oliver, Rydén, Lars, Standl, Eberhard, and Ceriello, Antonio
- Subjects
CLINICAL trials ,DIABETES ,ENDOCRINE diseases ,GLUCOSE ,NUTRITION disorders - Abstract
Cardiovascular disease (CVD) is one of the most common diabetes-associated complications, as well as a leading cause for death in type 2 diabetes patients (T2D). Despite the well-known correlation between the two, up until the 2008 FDA industry guidance for licensing of new anti-hyperglycemic drugs, which required an investigation of cardiovascular outcomes (CVO) of glucose-lowering agents, only a few studies had looked into the relationship between glucose lowering drugs and cardiovascular (CV) risk. Thereafter, CVOT design has focused on non-inferiority short-term studies on high-risk patient populations aiming at capturing CV safety issues. Despite the wealth of information and useful data provided by CVOTs, this approach still suffers from certain limitations. The present review will condense the main results of the most recently completed CVOTs, reflect on the lessons learned, discuss on the issues presented by current CVOT design and offer some suggestions for improvement. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
43. Are there time and cost savings by using telemanagement for patients on intensified insulin therapy?: A randomised, controlled trial
- Author
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Biermann, Eberhard, Dietrich, Wolfgang, Rihl, Julian, and Standl, Eberhard
- Subjects
- *
TELEMEDICINE , *PEOPLE with diabetes - Abstract
Background: Patients with insulin dependent diabetes require frequent advice if their metabolic control is not optimal. This study focuses on the fiscal and administrative aspects of telemanagement, which was used to establish a supervised autonomy of patients on intensified insulin therapy. Methods: A prospective, randomised trial with 43 patients on intensified insulin therapy was conducted. Travelling distance to the diabetes centre was 50 min one way; all patients had undergone a diabetes education course with lessons in dose adaptation. Patients were randomly assigned to telecare (n=27) or conventional care (n=16). They used BG-meters with a storage capacity of 120 values (Precision QID™ Abbott/Medisense) and transmitted their data over a combined modem/interface via telephone line to the diabetes centre. Data were displayed and stored by a customised software (Precision Link Plus™, Abbott/Medisense). Advice for proper dose adjustment was given by telephone. Results: Average time needed for instruction in the telemedical system was 15 min. Data were transmitted every 1–3 weeks and a teleconsultation was performed by phone every 2–4 weeks, depending on the extent of specific problems. On average, personal visits in the control group were performed once a month. Physician''s time expenditure for telemanagement, compared to conventional advice was moderately higher (50 vs. 42 min per month). A substantial amount of time on the patients side could be saved through replacing personal communications by telephone contacts and data transmission reduction (96 vs. 163 min/month including data transmission time). Setting up an optimal telemanagement scenario, a cost analysis was carried out yielding savings of ≈650 EURO per year per patient. HbA1c dropped significantly from 8.2 to 7.0% after 8 months of observation, but there was no significant difference between the intervention and control groups. Major technical problems with the telematic system did not occur during the study. Conclusions: Telemanagement of insulin-requiring diabetic patients is a cost and time saving procedure for the patients and results in metabolic control comparable to conventional outpatient management. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
44. Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
- Author
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El Hajj, Nady, Schneider, Eberhard, Lehnen, Harald, and Haaf, Thomas
- Subjects
EPIGENETICS ,ENVIRONMENTAL exposure ,FETAL nutrition ,DIABETES ,NEUROENDOCRINE cells ,METABOLISM ,ANIMAL models in research - Abstract
The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as 'developmental origins of health and disease (DOHAD)' or 'Barker' hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene- environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10-20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
45. Longitudinal Assessments of Erythropoietin-Stimulating Agent Responsiveness and the Association with Specific Clinical Outcomes in Dialysis Patients.
- Author
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Schneider, andreas, Gutjahr-Lengsfeld, Lena, Ritz, Eberhard, Scharnagl, Hubert, Gelbrich, Götz, Pilz, Stefan, Macdougall, Iain C., Wanner, Christoph, and Drechsler, Christiane
- Subjects
BLOOD doping ,HEMATOPOIETIC growth factors ,ERYTHROPOIETIN ,HEMODIALYSIS patients ,MEDICAL care - Abstract
Background: Dose requirements of erythropoietin-stimulating agents (ESAs) can vary considerably over time and may be associated with cardiovascular outcomes. We aimed to longitudinally assess ESA responsiveness over time and to investigate its association with specific clinical end points in a time-dependent approach. Methods: The German Diabetes and Dialysis study (4D study) included 1,255 diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those patients, the erythropoietin resistance index (ERI) was assessed every 6 months during a median follow-up of 4 years. The association between the ERI and cardiovascular end points was analyzed by time-dependent Cox regression analyses with repeated ERI measures. Results: Patients had a mean age of 66 ± 8.2 years; 53% were male. During follow-up, a total of 495 patients died, of whom 136 died of sudden death and 102 of infectious death. The adjusted and time-dependent risk for sudden death was increased by 19% per 5-unit increase in the ERI (hazard ratio, HR = 1.19, 95% confidence interval, CI = 1.07-1.33). Similarly, mortality increased by 25% (HR = 1.25, 95% CI = 1.18-1.32) and infectious death increased by 27% (HR = 1.27, 95% CI = 1.13-1.42). Further analysis revealed that lower 25-hydroxyvitamin D levels were associated with lower ESA responsiveness (p = 0.046). Conclusions: In diabetic dialysis patients, we observed that time-varying erythropoietin resistance is associated with sudden death, infectious complications and all-cause mortality. Low 25-hydroxyvitamin D levels may contribute to a lower ESA responsiveness. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
46. The Sodium-Glucose Co-Transporter 2 Inhibitor Empagliflozin Improves Diabetes-Induced Vascular Dysfunction in the Streptozotocin Diabetes Rat Model by Interfering with Oxidative Stress and Glucotoxicity.
- Author
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Oelze, Matthias, Kröller-Schön, Swenja, Welschof, Philipp, Jansen, Thomas, Hausding, Michael, Mikhed, Yuliya, Stamm, Paul, Mader, Michael, Zinßius, Elena, Agdauletova, Saule, Gottschlich, Anna, Steven, Sebastian, Schulz, Eberhard, Bottari, Serge P., Mayoux, Eric, Münzel, Thomas, and Daiber, Andreas
- Subjects
SODIUM-glucose cotransporters ,EMPAGLIFLOZIN ,DIABETES ,VASCULAR diseases ,STREPTOZOTOCIN ,LABORATORY rats ,OXIDATIVE stress - Abstract
Objective: In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. Methods: Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 7 weeks. Vascular function was assessed by isometric tension recording, oxidative stress parameters by chemiluminescence and fluorescence techniques, protein expression by Western blot, mRNA expression by RT-PCR, and islet function by insulin ELISA in serum and immunohistochemical staining of pancreatic tissue. Advanced glycation end products (AGE) signaling was assessed by dot blot analysis and mRNA expression of the AGE-receptor (RAGE). Results: Treatment with empagliflozin reduced blood glucose levels, normalized endothelial function (aortic rings) and reduced oxidative stress in aortic vessels (dihydroethidium staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence) of diabetic rats. Additionally, the pro-inflammatory phenotype and glucotoxicity (AGE/RAGE signaling) in diabetic animals was reversed by SGLT2i therapy. Conclusions: Empagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction, reduces oxidative stress and improves the metabolic situation in type 1 diabetic rats. These preclinical observations illustrate the therapeutic potential of this new class of antidiabetic drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
47. On the potential of acarbose to reduce cardiovascular disease.
- Author
-
Standl, Eberhard, Theodorakis, Michael J., Erbach, Michael, Schnell, Oliver, and Tuomilehto, Jaakko
- Subjects
- *
ACARBOSE , *CARDIOVASCULAR diseases , *BLOOD sugar , *DIABETES , *GLUCOSIDASE inhibitors - Abstract
In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted - though not undisputed - the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
48. Promotion of Autoimmune Diabetes by Cereal Diet in the Presence or Absence of Microbes Associated With Gut Immune Activation, Regulatory Imbalance, and Altered Cathelicidin Antimicrobial Peptide.
- Author
-
Patrick, Christopher, Gen-Sheng Wang, Lefebvre, David E., Crookshank, Jennifer A., Sonier, Brigitte, Eberhard, Chandra, Mojibian, Majid, Kennedy, Christopher R., Brooks, Stephen P. J., Kalmokoff, Martin L., Maglio, Mariantonia, Troncone, Riccardo, Poussier, Philippe, and Scott, Fraser W.
- Subjects
GASTROINTESTINAL system ,TYPE 1 diabetes ,DIABETES ,LABORATORY rats ,GENE expression ,T cells ,MESSENGER RNA - Abstract
We are exposed to millions of microbial and dietary antigens via the gastrointestinal tract, which likely play a key role in type 1 diabetes (T1D). We differentiated the effects of these two major environmental factors on gut immunity and T1D. Diabetes-prone BioBreeding (BBdp) rats were housed in specific pathogen-free (SPF) or germ-free (GF) conditions and weaned onto diabetes- promoting cereal diets or a protective low-antigen hydrolyzed casein (HC) diet, and T1D incidence was monitored. Fecal microbiota 16S rRNA genes, immune cell distribution, and gene expression in the jejunum were analyzed. T1D was highest in cereal-SPF (65%) and cereal-GF rats (53%) but inhibited and delayed in HC-fed counterparts. Nearly all HC-GF rats remained diabetes-free, whereas HC-fed SPF rats were less protected (7 vs. 29%). Bacterial communities differed in SPF rats fed cereal compared with HC. Cereal-SPF rats displayed increased gut CD3
+ and CD8α+ lymphocytes, ratio of Ifng to Il4 mRNA, and Lck expression, indicating T-cell activation. The ratio of CD3+ T cells expressing the Treg marker Foxp3+ was highest in HC-GF and lowest in cereal-SPF rats. Resident CD163+ M2 macrophages were increased in HC-protected rats. The cathelicidin antimicrobial peptide (Camp) gene was upregulated in the jejunum of HC diet-protected rats, and CAMP+ cells colocalized with CD163. A cereal diet was a stronger promoter of T1D than gut microbes in association with impaired gut immune homeostasis. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
49. Effect of diabetes mellitus on corneal biomechanics and measurement of intraocular pressure.
- Author
-
Scheler, Annabelle, Spoerl, Eberhard, and Boehm, Andreas G.
- Subjects
- *
DIABETES , *INTRAOCULAR pressure , *CORNEAL topography , *PEOPLE with diabetes , *BLOOD sugar monitoring , *OPHTHALMOLOGY - Abstract
. Purpose: To determine whether corneal hysteresis (CH) and corneal resistance factor (CRF) are altered in diabetes and whether these parameters are related to HbA1c. Methods: One randomly chosen eye of 35 healthy subjects and 31 patients with diabetes was examined. Patients with diabetes were divided into group 1 with HbA1c <7% ( n = 14) and group 2 with HbA1c ≥7% ( n = 17). CH and CRF were measured using ocular response analyzer (ORA); central corneal thickness (CCT) using ultrasound pachymetry; increased intraocular pressure (IOP) using Goldmann tonometer (IOPGAT), Pascal dynamic contour tonometer (IOPpasc), and ORA (IOPcc). As CH and CRF are dependent on IOP and CCT, they were adjusted for IOP and CCT resulting in CHcorr and CRFcorr. Results: Mean HbA1c was 5.44 ± 0.46% in healthy subjects, 6.00 ± 0.78% in diabetic group 1, 8.58 ± 2.44% in group 2. CHcorr (p = 0.071) and CRFcorr (p = 0.067) were not statistically significantly different between healthy subjects and diabetic group 1, but significantly lower in healthy subjects compared to diabetic group 2 [CHcorr (p = 0.031), CRFcorr (p = 0.029)]. IOPpasc (p = 0.012), IOPGAT (p = 0.032) and HbA1c (p = 0.0001) were statistically significantly different between healthy subjects and all patients with diabetes (groups 1 + 2), but not age, sex and CCT. Over all patients with diabetes, CHcorr (p = 0.012, R2 = 0.197) and CRFcorr (p = 0.008, R2 = 0.217) were correlated to HbA1c but not in healthy subjects [CHcorr (p = 0.931, R2 = 0.0001), CRFcorr (p = 0.837, R2 = 0.001)]. Conclusion: In poorly controlled diabetics, CHcorr and CRFcorr are significantly higher compared with those of the healthy subjects and patients with well-controlled diabetes. In diabetes, CHcorr and CRFcorr are correlated to HbA1c, suggesting that the biomechanical properties of the cornea are altered depending on the glucose control. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
50. Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes.
- Author
-
Jain, Deepak, Jain, Ruchi, Eberhard, Daniel, Eglinger, Jan, Bugliani, Marco, Piemonti, Lorenzo, Marchetti, Piero, and Lammert, Eckhard
- Abstract
Elderly patients often suffer from multiple age-related diseases. Here we show that the expression of DJ-1, an antioxidant protein with reduced expression in the central nervous system of patients with Parkinson's disease, is reduced in pancreatic islets of patients with type 2 diabetes mellitus (T2DM). In contrast, under non-diabetic conditions, DJ-1 expression increases in mouse and human islets during aging. In mouse islets, we show that DJ-1 prevents an increase in reactive oxygen species levels as the mice age. This antioxidant function preserves mitochondrial integrity and physiology, prerequisites for glucose-stimulated insulin secretion. Accordingly, DJ-1-deficient mice develop glucose intolerance and reduced β cell area as they age or gain weight. Our data suggest that DJ-1 is more generally involved in age- and lifestyle-related human diseases and show for the first time that DJ-1 plays a key role in glucose homeostasis and might serve as a novel drug target for T2DM. [ABSTRACT FROM PUBLISHER]
- Published
- 2012
- Full Text
- View/download PDF
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