Elsa Heyman1, Frédéric Daussin2, Valerie Wieczorek3, Robert Caiazzo4,5, Régis Matran6, Phanélie Berthon7, Julien Aucouturier2, Serge Berthoin2, Aurélien Descatoire8, Erwan Leclair2,9, Gaëlle Marais2, Adrien Combes2, Pierre Fontaine10, Sémah Tagougui2,11. 1. EA7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, Lille, France elsa.heyman@univ-lille.fr. 2. EA7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, Lille, France. 3. PRM Department, University Hospital of Lille, Lille, France. 4. Service de Chirurgie Générale et Endocrinienne, University Hospital of Lille, Lille, France. 5. UMR_1190 Recherche Translationnelle sur le Diabète, Faculté de Médecine de Lille, INSERM, Lille, France. 6. Department of Physiology, EA 2689 and IFR 22, Lille, France. 7. Inter-university Laboratory of Human Movement Sciences EA7424, University of Savoie Mont Blanc, Chambéry, France. 8. Regional Hospital Center of Roubaix, Roubaix, France. 9. Réseau québécois de recherche sur la douleur, Université de Sherbrooke, Montreal, Quebec, Canada. 10. Department of Diabetology, Lille University Hospital, EA 4489, Lille, France. 11. Metabolic Diseases, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada.
Abstract
OBJECTIVE: Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach. RESEARCH DESIGN AND METHODS: We compared 16 adults with T1D with 16 strictly matched healthy control subjects. We assessed lung diffusion capacity for carbon monoxide and nitric oxide, exercise-induced changes in arterial O2 content (SaO2, PaO2, hemoglobin), muscle blood volume, and O2 extraction (via near-infrared spectroscopy). We analyzed blood samples for metabolic and hormonal vasoactive moieties and factors that are able to shift the O2-hemoglobin dissociation curve. Mitochondrial oxidative capacities were assessed in permeabilized vastus lateralis muscle fibers. RESULTS: Lung diffusion capacity and arterial O2 transport were normal in patients with T1D. However, those patients displayed blunted exercise-induced increases in muscle blood volume, despite higher serum insulin, and in O2 extraction, despite higher erythrocyte 2,3-diphosphoglycerate. Although complex I- and complex II-supported mitochondrial respirations were unaltered, complex IV capacity (relative to complex I capacity) was impaired in patients with T1D, and this was even more apparent in those with long-standing diabetes and high HbA1c. [Formula: see text]O2max was lower in patients with T1D than in the control subjects. CONCLUSIONS: Early defects in microvascular delivery of blood to skeletal muscle and in complex IV capacity in the mitochondrial respiratory chain may negatively impact aerobic fitness. These findings are clinically relevant considering the main role of skeletal muscle oxidation in whole-body glucose disposal.
OBJECTIVE: Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach. RESEARCH DESIGN AND METHODS: We compared 16 adults with T1D with 16 strictly matched healthy control subjects. We assessed lung diffusion capacity for carbon monoxide and nitric oxide, exercise-induced changes in arterial O2 content (SaO2, PaO2, hemoglobin), muscle blood volume, and O2 extraction (via near-infrared spectroscopy). We analyzed blood samples for metabolic and hormonal vasoactive moieties and factors that are able to shift the O2-hemoglobin dissociation curve. Mitochondrial oxidative capacities were assessed in permeabilized vastus lateralis muscle fibers. RESULTS: Lung diffusion capacity and arterial O2 transport were normal in patients with T1D. However, those patients displayed blunted exercise-induced increases in muscle blood volume, despite higher serum insulin, and in O2 extraction, despite higher erythrocyte 2,3-diphosphoglycerate. Although complex I- and complex II-supported mitochondrial respirations were unaltered, complex IV capacity (relative to complex I capacity) was impaired in patients with T1D, and this was even more apparent in those with long-standing diabetes and high HbA1c. [Formula: see text]O2max was lower in patients with T1D than in the control subjects. CONCLUSIONS: Early defects in microvascular delivery of blood to skeletal muscle and in complex IV capacity in the mitochondrial respiratory chain may negatively impact aerobic fitness. These findings are clinically relevant considering the main role of skeletal muscle oxidation in whole-body glucose disposal.
Authors: Cynthia M F Monaco; Mark A Tarnopolsky; Athan G Dial; Joshua P Nederveen; Irena A Rebalka; Maria Nguyen; Lauren V Turner; Christopher G R Perry; Vladimir Ljubicic; Thomas J Hawke Journal: Diabetologia Date: 2021-08-14 Impact factor: 10.122
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