Christian Herder1,2, Julia M Kannenberg1,2, Cornelia Huth2,3, Maren Carstensen-Kirberg1,2, Wolfgang Rathmann2,4, Wolfgang Koenig5,6, Alexander Strom1,2, Gidon J Bönhof1, Margit Heier3, Barbara Thorand2,3, Annette Peters2,3, Michael Roden1,2,7, Christa Meisinger2,3,8, Dan Ziegler1,2,7. 1. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 2. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. 3. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 4. Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 5. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. 6. German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany. 7. Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. 8. Chair of Epidemiology, Ludwig-Maximilian-Universität München, UNIKA-T Augsburg, Augsburg, Germany.
Abstract
BACKGROUND: Oxidative stress has been proposed as important pathomechanism of cardiometabolic diseases and distal sensorimotor polyneuropathy (DSPN). However, the relevance of biomarkers of oxidative stress has not been investigated in this context. Therefore, this study aimed to assess the association of the prooxidant myeloperoxidase (MPO) and the antioxidant extracellular superoxide dismutase (SOD3) with cardiometabolic risk factors and with prevalence and incidence of DSPN. METHODS: Cross-sectional analyses comprised 1069 participants (40.3% with prediabetes and 20.5% with type 2 diabetes) of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-2008), 181 of whom had DSPN at baseline. Prospective analyses included 524 individuals without DSPN at baseline who also participated in the KORA FF4 study (2013-2014), 132 of whom developed DSPN during the 6.5-year follow-up. Serum MPO and SOD3 were measured by ELISA, and their association with cardiometabolic risk factors and DSPN were estimated by using linear and logistic regression analyses. RESULTS: Higher MPO and SOD levels showed multiple positive associations with cardiometabolic risk factors including age, indices of obesity, insulin resistance, serum lipids, renal dysfunction, and biomarkers of inflammation. Higher MPO levels were associated with prevalent DSPN (fully adjusted OR 1.38 [95% CI 1.10; 1.72] per doubling of MPO). Higher baseline SOD3 levels were related to incident DSPN (age and sex-adjusted OR 2.14 [1.02; 4.48] per doubling of SOD3), which was partially explained by cardiometabolic risk factors. CONCLUSIONS: Systemic levels of both pro- and antioxidant enzymes appear involved in cardiometabolic risk and development of DSPN.
BACKGROUND: Oxidative stress has been proposed as important pathomechanism of cardiometabolic diseases and distal sensorimotor polyneuropathy (DSPN). However, the relevance of biomarkers of oxidative stress has not been investigated in this context. Therefore, this study aimed to assess the association of the prooxidant myeloperoxidase (MPO) and the antioxidant extracellular superoxide dismutase (SOD3) with cardiometabolic risk factors and with prevalence and incidence of DSPN. METHODS: Cross-sectional analyses comprised 1069 participants (40.3% with prediabetes and 20.5% with type 2 diabetes) of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-2008), 181 of whom had DSPN at baseline. Prospective analyses included 524 individuals without DSPN at baseline who also participated in the KORA FF4 study (2013-2014), 132 of whom developed DSPN during the 6.5-year follow-up. Serum MPO and SOD3 were measured by ELISA, and their association with cardiometabolic risk factors and DSPN were estimated by using linear and logistic regression analyses. RESULTS: Higher MPO and SOD levels showed multiple positive associations with cardiometabolic risk factors including age, indices of obesity, insulin resistance, serum lipids, renal dysfunction, and biomarkers of inflammation. Higher MPO levels were associated with prevalent DSPN (fully adjusted OR 1.38 [95% CI 1.10; 1.72] per doubling of MPO). Higher baseline SOD3 levels were related to incident DSPN (age and sex-adjusted OR 2.14 [1.02; 4.48] per doubling of SOD3), which was partially explained by cardiometabolic risk factors. CONCLUSIONS: Systemic levels of both pro- and antioxidant enzymes appear involved in cardiometabolic risk and development of DSPN.
Authors: Theresia Sarabhai; Lucia Mastrototaro; Sabine Kahl; Gidon J Bönhof; Marc Jonuscheit; Pavel Bobrov; Hisayuki Katsuyama; Rainer Guthoff; Martin Wolkersdorfer; Christian Herder; Sven G Meuth; Sven Dreyer; Michael Roden Journal: Diabetologia Date: 2022-09-30 Impact factor: 10.460
Authors: Cornelia Then; Chaterina Sujana; Christian Herder; Holger Then; Margit Heier; Christa Meisinger; Annette Peters; Wolfgang Koenig; Wolfgang Rathmann; Haifa Maalmi; Katrin Ritzel; Michael Roden; Michael Stumvoll; Barbara Thorand; Jochen Seissler Journal: Vasc Health Risk Manag Date: 2022-05-03
Authors: Christina Gar; Barbara Thorand; Christian Herder; Chaterina Sujana; Margit Heier; Christa Meisinger; Annette Peters; Wolfgang Koenig; Wolfgang Rathmann; Michael Roden; Michael Stumvoll; Haifa Maalmi; Thomas Meitinger; Holger Then; Jochen Seissler; Cornelia Then Journal: PLoS One Date: 2022-01-06 Impact factor: 3.240
Authors: Cornelia Then; Christian Herder; Holger Then; Barbara Thorand; Cornelia Huth; Margit Heier; Christa Meisinger; Annette Peters; Wolfgang Koenig; Wolfgang Rathmann; Michael Roden; Michael Stumvoll; Haifa Maalmi; Thomas Meitinger; Andreas Lechner; Jürgen Scherberich; Jochen Seissler Journal: Clin Kidney J Date: 2020-09-06