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Muscle Oxygen Supply and Use in Type 1 Diabetes, From Ambient Air to the Mitochondrial Respiratory Chain: Is There a Limiting Step?
- Source :
- Diabetes Care, Diabetes Care, American Diabetes Association, 2019, pp.dc191125. ⟨10.2337/dc19-1125⟩, Diabetes Care, 2019, pp.dc191125. ⟨10.2337/dc19-1125⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
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. 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.
- Subjects :
- Male
Oxyhemoglobins/analysis
Endocrinology, Diabetes and Metabolism
[SDV]Life Sciences [q-bio]
Blood volume
Oxygen Consumption/physiology
0302 clinical medicine
Exercise/physiology
Diabetes Mellitus, Type 1/metabolism
030212 general & internal medicine
Spectroscopy, Near-Infrared
Oxygen–haemoglobin dissociation curve
3. Good health
[SDV] Life Sciences [q-bio]
Mitochondrial respiratory chain
medicine.anatomical_structure
RESPIRATION
young adult
Female
Adult
medicine.medical_specialty
Adolescent
Vastus lateralis muscle
Cell Respiration
030209 endocrinology & metabolism
Case-control studies
Electron Transport
03 medical and health sciences
Oxygen Consumption
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Aerobic exercise
Humans
Muscle, Skeletal
Exercise
Advanced and Specialized Nursing
Muscle, Skeletal/metabolism
business.industry
Skeletal muscle
Mitochondria, Muscle/metabolism
medicine.disease
Mitochondria, Muscle
Oxygen/analysis
Oxygen
Endocrinology
Diabetes Mellitus, Type 1
Oxyhemoglobins
Hemoglobin
business
Electron Transport/physiology
Subjects
Details
- Language :
- English
- ISSN :
- 01495992
- Database :
- OpenAIRE
- Journal :
- Diabetes Care, Diabetes Care, American Diabetes Association, 2019, pp.dc191125. ⟨10.2337/dc19-1125⟩, Diabetes Care, 2019, pp.dc191125. ⟨10.2337/dc19-1125⟩
- Accession number :
- edsair.doi.dedup.....5d3f23c53ebebc2d298e4beafe3e4f18