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  1. Article: Lower serum extracellular superoxide dismutase levels are associated with polyneuropathy in recent-onset diabetes

    Roden, Michael / Ziegler, Dan

    Experimental & molecular medicine, 49:e394

    2017  

    Abstract: Increased oxidative stress is implicated in the pathogenesis of experimental diabetic neuropathy, but translational evidence in recent-onset diabetes is scarce. We aimed to determine whether markers of systemic oxidative stress are associated with ... ...

    Institution Deutsches Diabetes-Zentrum
    Abstract Increased oxidative stress is implicated in the pathogenesis of experimental diabetic neuropathy, but translational evidence in recent-onset diabetes is scarce. We aimed to determine whether markers of systemic oxidative stress are associated with diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. In this cross-sectional study, we measured serum concentrations of extracellular superoxide dismutase (SOD3), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) in 107 type 1 and 215 type 2 diabetes patients from the German Diabetes Study baseline cohort and 37 glucose-tolerant individuals (controls). DSPN was defined by electrophysiological and clinical criteria (Toronto Consensus, 2011). SOD3 and GSH concentrations were lower in individuals with type 1 and type 2 diabetes compared with concentrations in controls (P<0.0001). In contrast, the TBARS concentration was higher in participants with type 1 diabetes and type 2 diabetes compared with levels in controls (P<0.0001). In addition, the SOD3 concentration was higher in participants with type 1 diabetes compared to concentrations in those with type 2 diabetes (P<0.0001). A low SOD3 concentration was associated with DSPN in individuals with type 1 diabetes (β=−0.306, P=0.002), type 2 diabetes (β=−0.164, P=0.017), and in both groups combined (β=−0.206, P=0.0003). Lower SOD3 concentrations were associated with decreased motor nerve conduction velocity (NCV) in men and, to a lesser degree, with reduced sensory NCV in women with diabetes. In conclusion, several biomarkers of oxidative stress are altered in recent-onset diabetes, with only a lower SOD3 concentration being linked to the presence of DSPN, suggesting a role for reduced extracellular antioxidative defense against superoxide in the early development of DSPN.
    Keywords Diabetes complications ; Predictive markers
    Language English
    Document type Article
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  2. Article: Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

    Bierwagen, Alessandra / Ziegler, Dan / Roden, Michael

    Molecular metabolism, 7:71-79

    2017  

    Abstract: OBJECTIVE: Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus ... ...

    Institution Deutsches Diabetes-Zentrum
    Abstract OBJECTIVE: Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes models. We examined the effects of 14-min taVNS vs sham stimulation by Cerbomed Nemos® on glucose metabolism, lipids, and hepatic energy homeostasis in fasted healthy humans (n = 10, age 51 ± 6 yrs, BMI 25.5 ± 2.7 kg/m2). METHODS: Heart rate variability (HRV), reflecting sympathetic and parasympathetic nerve activity, was measured before, during and after taVNS or sham stimulation. Endogenous glucose production was determined using [6,6-2H2]glucose, and hepatic concentrations of triglycerides (HCL), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified from 1H/31P magnetic resonance spectroscopy at baseline and for 180 min following stimulation. RESULTS: taVNS did not affect circulating glucose, free fatty acids, insulin, glucagon, or pancreatic polypeptide. Rates of endogenous glucose production (P = 0.79), hepatic HCL, ATP, and Pi were also not different (P = 0.91, P = 0.48 and P = 0.24) between taVNS or sham stimulation. Hepatic HCL, ATP, and Pi remained constant during prolonged fasting for 3 h. No changes in heart rate or shift in cardiac autonomic function from HRV towards sympathetic or parasympathetic predominance were detected. CONCLUSION: Non-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans.
    Keywords Hepatic energy metabolism ; Hepatic insulin sensitivity ; Liver fat content ; Vagus nerve stimulation
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  3. Article: Spatial analysis improves the detection of early corneal nerve fiber loss in patients with recently diagnosed type 2 diabetes

    Ziegler, Dan / PAPANAS, NIKOLAOS / Roden, Michael

    PLOS ONE, 12(3):e0173832

    2017  

    Abstract: Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the ... ...

    Institution Deutsches Diabetes-Zentrum
    Abstract Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the distribution of corneal nerve branching points (CNBPs) may contribute to improving the detection of early CNF loss. We hypothesized that early CNF decline follows a clustered rather than random distribution pattern of CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed in a cross-sectional study including 86 patients recently diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern analysis (SPPA) including 10 indices and functional statistics. Compared to controls, patients with diabetes showed lower CNBP density and higher nearest neighbor distances, and all SPPA parameters indicated increased clustering of CNBPs (all P<0.05). SPPA parameters were abnormally increased >97.5th percentile of controls in up to 23.5% of patients. When combining an individual SPPA parameter with CNFL, ≥1 of 2 indices were >99th or <1st percentile of controls in 28.6% of patients compared to 2.1% of controls, while for the conventional CNFL/CNFD/CNBD combination the corresponding rates were 16.3% vs 2.1%. SPPA parameters correlated with CNFL and several NCS and QST indices in the controls (all P<0.001), whereas in patients with diabetes these correlations were markedly weaker or lost. In conclusion, SPPA reveals increased clustering of early CNF loss and substantially improves its detection when combined with a conventional CCM measure in patients with recently diagnosed type 2 diabetes.
    Keywords Cornea ; Diabetes mellitus ; Morphometry ; Neuropathy ; Nerve fibers ; Spatial analysis ; Permutation ; Type 2 diabetes
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  4. Book: Cardiovascular genetics and genomics

    Roden, Dan M.

    (The AHA clinical series)

    2009  

    Institution American Heart Association
    Author's details ed. by Dan Roden
    Series title The AHA clinical series
    Keywords Heart Diseases / genetics ; Heart Diseases / therapy ; Cardiovascular Diseases / genetics ; Cardiovascular Diseases / therapy ; Genomics / methods ; Pharmacogenetics
    Language English
    Size XVII, 265 S. : Ill., graph. Darst.
    Publisher Wiley-Blackwell
    Publishing place Chichester
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT015540956
    ISBN 978-1-4051-7540-1 ; 1-4051-7540-0
    Database Catalogue ZB MED Medicine, Health

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  5. Article ; Online: Clopidogrel Pharmacogenetics - Why the Wait?

    Roden, Dan M

    The New England journal of medicine

    2019  Volume 381, Issue 17, Page(s) 1677–1678

    MeSH term(s) Clopidogrel ; Genotype ; Percutaneous Coronary Intervention ; Pharmacogenetics ; Platelet Aggregation Inhibitors ; Ticlopidine
    Chemical Substances Platelet Aggregation Inhibitors ; Clopidogrel (A74586SNO7) ; Ticlopidine (OM90ZUW7M1)
    Language English
    Publishing date 2019-10-22
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMe1911496
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  6. Article ; Online: A current understanding of drug-induced QT prolongation and its implications for anticancer therapy.

    Roden, Dan M

    Cardiovascular research

    2019  Volume 115, Issue 5, Page(s) 895–903

    Abstract: The QT interval, a global index of ventricular repolarization, varies among individuals and is influenced by diverse physiologic and pathophysiologic stimuli such as gender, age, heart rate, electrolyte concentrations, concomitant cardiac disease, and ... ...

    Abstract The QT interval, a global index of ventricular repolarization, varies among individuals and is influenced by diverse physiologic and pathophysiologic stimuli such as gender, age, heart rate, electrolyte concentrations, concomitant cardiac disease, and other diseases such as diabetes. Many drugs produce a small but reproducible effect on QT interval but in rare instances this is exaggerated and marked QT prolongation can provoke the polymorphic ventricular tachycardia 'torsades de pointes', which can cause syncope or sudden cardiac death. The generally accepted common mechanism whereby drugs prolong QT is block of a key repolarizing potassium current in heart, IKr, generated by expression of KCNH2, also known as HERG. Thus, evaluation of the potential that a new drug entity may cause torsades de pointes has relied on exposure of normal volunteers or patients to drug at usual and high concentrations, and on assessment of IKr block in vitro. More recent work, focusing on anticancer drugs with QT prolonging liability, is defining new pathways whereby drugs can prolong QT. Notably, the in vitro effects of some tyrosine kinase inhibitors to prolong cardiac action potentials (the cellular correlate of QT) can be rescued by intracellular phosphatidylinositol 3,4,5-trisphosphate, the downstream effector of phosphoinositide 3-kinase. This finding supports a role for inhibition of this enzyme, either directly or by inhibition of upstream kinases, to prolong QT through mechanisms that are being worked out, but include enhanced inward 'late' sodium current during the plateau of the action potential. The definition of non-IKr-dependent pathways to QT prolongation will be important for assessing risk, not only with anticancer therapies but also with other QT prolonging drugs and for generating a refined understanding how variable activity of intracellular signalling systems can modulate QT and associated arrhythmia risk.
    MeSH term(s) Action Potentials ; Animals ; Antineoplastic Agents/adverse effects ; Genetic Predisposition to Disease ; Heart Conduction System/drug effects ; Heart Conduction System/physiopathology ; Heart Rate/drug effects ; Humans ; Long QT Syndrome/chemically induced ; Long QT Syndrome/genetics ; Long QT Syndrome/physiopathology ; Membrane Transport Proteins/genetics ; Molecular Targeted Therapy/adverse effects ; Prognosis ; Risk Assessment ; Risk Factors
    Chemical Substances Antineoplastic Agents ; Membrane Transport Proteins
    Language English
    Publishing date 2019-01-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvz013
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  7. Article ; Online: John A. Oates: A Founding Father of Clinical Pharmacology.

    Roden, Dan M

    Clinical pharmacology and therapeutics

    2019  Volume 106, Issue 6, Page(s) 1155–1157

    MeSH term(s) History, 20th Century ; History, 21st Century ; Pharmacology, Clinical/history
    Language English
    Publishing date 2019-09-16
    Publishing country United States
    Document type Biography ; Historical Article ; News
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.1614
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    Zs.A 20: Show issues Location:
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  8. Book: A re-examination of the relationship between drug induced QT-interval prolongation and proarrhythmic risk

    Roden, Dan M.

    (Europace ; 9, Suppl. 4)

    2007  

    Title variant A re-examination of the relationship between drug-induced QT-interval prolongation and proarrhythmic risk
    Author's details guest ed.: Dan M. Roden
    Series title Europace ; 9, Suppl. 4
    Collection
    Language English
    Size iv44 S. : graph. Darst.
    Publisher Oxford Univ. Press
    Publishing place Oxford
    Publishing country United States
    Document type Book
    HBZ-ID HT015299491
    Database Catalogue ZB MED Medicine, Health

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    Zs A 5434 -9,Suppl.4- not available for loan Zeitschriften-Lesesaal

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  9. Article ; Online: The Shape of Ventricular Tachycardia.

    Stevenson, William G / Tandri, Harikrishna / Roden, Dan M

    Circulation

    2023  Volume 148, Issue 18, Page(s) 1368–1370

    MeSH term(s) Humans ; Tachycardia, Ventricular/diagnosis ; Tachycardia, Ventricular/therapy ; Arrhythmias, Cardiac ; Electrocardiography
    Language English
    Publishing date 2023-10-30
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.123.066574
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  10. Article: Cohort profile: the German Diabetes Study (GDS)

    Herder, Christian / Icks, Andrea / Kuss, Oliver / Ziegler, Dan / Roden, Michael

    Cardiovascular diabetology, 15:59

    2016  

    Abstract: BACKGROUND: The German Diabetes Study (GDS) is a prospective longitudinal cohort study describing the impact of subphenotypes on the course of the disease. GDS aims at identifying prognostic factors and mechanisms underlying the development of related ... ...

    Institution Deutsches Diabetes-Zentrum
    Abstract BACKGROUND: The German Diabetes Study (GDS) is a prospective longitudinal cohort study describing the impact of subphenotypes on the course of the disease. GDS aims at identifying prognostic factors and mechanisms underlying the development of related comorbidities. STUDY DESIGN AND METHODS: The study comprises intensive phenotyping within 12 months after clinical diagnosis, at 5-year intervals for 20 years and annual telephone interviews in between. Dynamic tests, including glucagon, mixed meal, intravenous glucose tolerance and hyperinsulinemic clamp tests, serve to assess beta-cell function and tissue-specific insulin sensitivity. Magnetic resonance imaging and multinuclei spectroscopy allow quantifying whole-body fat distribution, tissue-specific lipid deposition and energy metabolism. Comprehensive analyses of microvascular (nerve, eye, kidney) and macrovascular (endothelial, cardiorespiratory) morphology and function enable identification and monitoring of comorbidities. The GDS biobank stores specimens from blood, stool, skeletal muscle, subcutaneous adipose tissue and skin for future analyses including multiomics, expression profiles and histology. Repeated questionnaires on socioeconomic conditions, patient-reported outcomes as quality of life, health-related behavior as physical activity and nutritional habits are a specific asset of GDS. This study will recruit 3000 patients and a group of humans without familiy history of diabetes. 237 type 1 and 456 type 2 diabetes patients have been already included.
    Keywords Beta cell function ; Diabetes comorbidities ; Insulin resistance ; Magnetic resonance spectroscopy ; Metabolic phenotyping
    Language English
    Document type Article
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