Maria Apostolopoulou1,2, Klaus Strassburger2,3, Christian Herder1,2, Birgit Knebel2,4, Jörg Kotzka2,4, Julia Szendroedi1,2,5, Michael Roden6,7,8. 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 for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. 4. Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. 5. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, c/o German Diabetes Center at Heinrich-Heine University, Auf dem Hennekamp 65, 40225, Düsseldorf, Germany. 6. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de. 7. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. michael.roden@ddz.uni-duesseldorf.de. 8. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, c/o German Diabetes Center at Heinrich-Heine University, Auf dem Hennekamp 65, 40225, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de.
Abstract
AIMS/HYPOTHESIS: Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake ([Formula: see text]) and/or metabolic flexibility (as given by ΔRQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that [Formula: see text] and ΔRQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships. METHODS: Near-normoglycaemic individuals with type 2 diabetes mellitus (n = 136) with a short known disease duration (<12 months) underwent cycling spiroergometry, indirect calorimetry and hyperinsulinaemic-euglycaemic clamp tests. RESULTS: Both [Formula: see text] (r = 0.39, p < 0.0001) and ΔRQ (r = 0.32, p < 0.0001) correlated positively with whole-body insulin sensitivity, even after adjusting for anthropometric variables, glycaemia and glucose-lowering medication, but not after adjusting for NEFA. [Formula: see text] further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, [Formula: see text] did not relate to ΔRQ, even after adjusting for whole-body insulin sensitivity. CONCLUSIONS/ INTERPRETATION: Oxidative capacity and metabolic flexibility are independent determinants of insulin sensitivity but are influenced by circulating NEFA in recent-onset type 2 diabetes. ClinicalTrial.gov registration no: NCT01055093.
AIMS/HYPOTHESIS: Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake ([Formula: see text]) and/or metabolic flexibility (as given by ΔRQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that [Formula: see text] and ΔRQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships. METHODS: Near-normoglycaemic individuals with type 2 diabetes mellitus (n = 136) with a short known disease duration (<12 months) underwent cycling spiroergometry, indirect calorimetry and hyperinsulinaemic-euglycaemic clamp tests. RESULTS: Both [Formula: see text] (r = 0.39, p < 0.0001) and ΔRQ (r = 0.32, p < 0.0001) correlated positively with whole-body insulin sensitivity, even after adjusting for anthropometric variables, glycaemia and glucose-lowering medication, but not after adjusting for NEFA. [Formula: see text] further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, [Formula: see text] did not relate to ΔRQ, even after adjusting for whole-body insulin sensitivity. CONCLUSIONS/ INTERPRETATION: Oxidative capacity and metabolic flexibility are independent determinants of insulin sensitivity but are influenced by circulating NEFA in recent-onset type 2 diabetes. ClinicalTrial.gov registration no: NCT01055093.
Entities:
Keywords:
Energy metabolism; Inflammation; Insulin sensitivity; Mitochondria; Muscle
Authors: Attila Brehm; Martin Krssak; Albrecht I Schmid; Peter Nowotny; Werner Waldhäusl; Michael Roden Journal: Diabetes Date: 2006-01 Impact factor: 9.461
Authors: Joris Hoeks; Noud A van Herpen; Marco Mensink; Esther Moonen-Kornips; Denis van Beurden; Matthijs K C Hesselink; Patrick Schrauwen Journal: Diabetes Date: 2010-06-23 Impact factor: 9.461
Authors: Julia Szendroedi; Toru Yoshimura; Esther Phielix; Chrysi Koliaki; Mellissa Marcucci; Dongyan Zhang; Tomas Jelenik; Janette Müller; Christian Herder; Peter Nowotny; Gerald I Shulman; Michael Roden Journal: Proc Natl Acad Sci U S A Date: 2014-06-16 Impact factor: 11.205
Authors: Timothy M Frayling; Nicholas J Timpson; Michael N Weedon; Eleftheria Zeggini; Rachel M Freathy; Cecilia M Lindgren; John R B Perry; Katherine S Elliott; Hana Lango; Nigel W Rayner; Beverley Shields; Lorna W Harries; Jeffrey C Barrett; Sian Ellard; Christopher J Groves; Bridget Knight; Ann-Marie Patch; Andrew R Ness; Shah Ebrahim; Debbie A Lawlor; Susan M Ring; Yoav Ben-Shlomo; Marjo-Riitta Jarvelin; Ulla Sovio; Amanda J Bennett; David Melzer; Luigi Ferrucci; Ruth J F Loos; Inês Barroso; Nicholas J Wareham; Fredrik Karpe; Katharine R Owen; Lon R Cardon; Mark Walker; Graham A Hitman; Colin N A Palmer; Alex S F Doney; Andrew D Morris; George Davey Smith; Andrew T Hattersley; Mark I McCarthy Journal: Science Date: 2007-04-12 Impact factor: 47.728
Authors: Tineke van de Weijer; Lauren Marie Sparks; Esther Phielix; Ruth Carla Meex; Noud Antonius van Herpen; Matthijs Karel C Hesselink; Patrick Schrauwen; Vera Bettina Schrauwen-Hinderling Journal: PLoS One Date: 2013-02-13 Impact factor: 3.240
Authors: Julia Szendroedi; Aaruni Saxena; Katharina S Weber; Klaus Strassburger; Christian Herder; Volker Burkart; Bettina Nowotny; Andrea Icks; Oliver Kuss; Dan Ziegler; Hadi Al-Hasani; Karsten Müssig; Michael Roden Journal: Cardiovasc Diabetol Date: 2016-04-07 Impact factor: 9.951
Authors: Karen R Jonscher; Michael S Stewart; Alba Alfonso-Garcia; Brian C DeFelice; Xiaoxin X Wang; Yuhuan Luo; Moshe Levi; Margaret J R Heerwagen; Rachel C Janssen; Becky A de la Houssaye; Ellen Wiitala; Garrett Florey; Raleigh L Jonscher; Eric O Potma; Oliver Fiehn; Jacob E Friedman Journal: FASEB J Date: 2016-12-22 Impact factor: 5.191
Authors: Maria Apostolopoulou; Lucia Mastrototaro; Sonja Hartwig; Dominik Pesta; Klaus Straßburger; Elisabetta de Filippo; Tomas Jelenik; Yanislava Karusheva; Sofiya Gancheva; Daniel Markgraf; Christian Herder; K Sreekumaran Nair; Andreas S Reichert; Stefan Lehr; Karsten Müssig; Hadi Al-Hasani; Julia Szendroedi; Michael Roden Journal: Sci Adv Date: 2021-10-08 Impact factor: 14.136
Authors: Rafael Zapata-Lamana; Carlos Henríquez-Olguín; Carlos Burgos; Roberto Meneses-Valdés; Igor Cigarroa; Claudio Soto; Valentín E Fernández-Elías; Sonia García-Merino; Rodrigo Ramirez-Campillo; Antonio García-Hermoso; Hugo Cerda-Kohler Journal: Front Physiol Date: 2018-09-18 Impact factor: 4.566
Authors: Robert M Edinburgh; Helen E Bradley; Nurul-Fadhilah Abdullah; Scott L Robinson; Oliver J Chrzanowski-Smith; Jean-Philippe Walhin; Sophie Joanisse; Konstantinos N Manolopoulos; Andrew Philp; Aaron Hengist; Adrian Chabowski; Frances M Brodsky; Francoise Koumanov; James A Betts; Dylan Thompson; Gareth A Wallis; Javier T Gonzalez Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958