OpenAccessBelV2, Pmc, Corpus, bibRecord, 000397

Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

Identifieur interne : 000397 ( Pmc/Corpus ); précédent : 000396; suivant : 000398

Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

Auteurs : Semah Tagougui ; Erwan Leclair ; Pierre Fontaine ; Régis Matran ; Gaelle Marais ; Julien Aucouturier ; Aurélien Descatoire ; Anne Vambergue ; Kahina Oussaidene ; Georges Baquet ; Elsa Heyman

Source :

Medicine and Science in Sports and Exercise [ 0195-9131 ] ; 2015.

RBID : PMC:4323553

Abstract

ABSTRACTPurpose

Aerobic fitness, as reflected by maximal oxygen (O₂) uptake (V˙O_2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA_1c) influence O₂ supply including O₂ delivery and release to active muscles during maximal exercise.

Methods

Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA_1c <7.0%; T1D-I, n = 12 with inadequate glycemic control, HbA_1c >8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O_2max. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O₂ transport and factors able to shift the oxyhemoglobin dissociation curve.

Results

Arterial O₂ content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O_2max was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A.

Conclusions

Poorly controlled patients displayed lower V˙O_2max and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O₂ affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323553

DOI: 10.1249/MSS.0000000000000424
PubMed: 24983346
PubMed Central: 4323553

Links to Exploration step

PMC:4323553

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes</title>
<author><name sortKey="Tagougui, Semah" sort="Tagougui, Semah" uniqKey="Tagougui S" first="Semah" last="Tagougui">Semah Tagougui</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Leclair, Erwan" sort="Leclair, Erwan" uniqKey="Leclair E" first="Erwan" last="Leclair">Erwan Leclair</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fontaine, Pierre" sort="Fontaine, Pierre" uniqKey="Fontaine P" first="Pierre" last="Fontaine">Pierre Fontaine</name>
<affiliation><nlm:aff id="aff1">Department of Diabetology, Lille University Hospital, EA 4489, Lille, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matran, Regis" sort="Matran, Regis" uniqKey="Matran R" first="Régis" last="Matran">Régis Matran</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff1">Department of Physiology, EA 2689 and IFR 22, Lille, FRANCE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marais, Gaelle" sort="Marais, Gaelle" uniqKey="Marais G" first="Gaelle" last="Marais">Gaelle Marais</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Aucouturier, Julien" sort="Aucouturier, Julien" uniqKey="Aucouturier J" first="Julien" last="Aucouturier">Julien Aucouturier</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Descatoire, Aurelien" sort="Descatoire, Aurelien" uniqKey="Descatoire A" first="Aurélien" last="Descatoire">Aurélien Descatoire</name>
<affiliation><nlm:aff id="aff1">Regional Hospital Centre of Roubaix, FRANCE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vambergue, Anne" sort="Vambergue, Anne" uniqKey="Vambergue A" first="Anne" last="Vambergue">Anne Vambergue</name>
<affiliation><nlm:aff id="aff1">Department of Diabetology, Lille University Hospital, EA 4489, Lille, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oussaidene, Kahina" sort="Oussaidene, Kahina" uniqKey="Oussaidene K" first="Kahina" last="Oussaidene">Kahina Oussaidene</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baquet, Georges" sort="Baquet, Georges" uniqKey="Baquet G" first="Georges" last="Baquet">Georges Baquet</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Heyman, Elsa" sort="Heyman, Elsa" uniqKey="Heyman E" first="Elsa" last="Heyman">Elsa Heyman</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24983346</idno>
<idno type="pmc">4323553</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323553</idno>
<idno type="RBID">PMC:4323553</idno>
<idno type="doi">10.1249/MSS.0000000000000424</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000397</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes</title>
<author><name sortKey="Tagougui, Semah" sort="Tagougui, Semah" uniqKey="Tagougui S" first="Semah" last="Tagougui">Semah Tagougui</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Leclair, Erwan" sort="Leclair, Erwan" uniqKey="Leclair E" first="Erwan" last="Leclair">Erwan Leclair</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fontaine, Pierre" sort="Fontaine, Pierre" uniqKey="Fontaine P" first="Pierre" last="Fontaine">Pierre Fontaine</name>
<affiliation><nlm:aff id="aff1">Department of Diabetology, Lille University Hospital, EA 4489, Lille, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matran, Regis" sort="Matran, Regis" uniqKey="Matran R" first="Régis" last="Matran">Régis Matran</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff1">Department of Physiology, EA 2689 and IFR 22, Lille, FRANCE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marais, Gaelle" sort="Marais, Gaelle" uniqKey="Marais G" first="Gaelle" last="Marais">Gaelle Marais</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Aucouturier, Julien" sort="Aucouturier, Julien" uniqKey="Aucouturier J" first="Julien" last="Aucouturier">Julien Aucouturier</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Descatoire, Aurelien" sort="Descatoire, Aurelien" uniqKey="Descatoire A" first="Aurélien" last="Descatoire">Aurélien Descatoire</name>
<affiliation><nlm:aff id="aff1">Regional Hospital Centre of Roubaix, FRANCE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vambergue, Anne" sort="Vambergue, Anne" uniqKey="Vambergue A" first="Anne" last="Vambergue">Anne Vambergue</name>
<affiliation><nlm:aff id="aff1">Department of Diabetology, Lille University Hospital, EA 4489, Lille, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oussaidene, Kahina" sort="Oussaidene, Kahina" uniqKey="Oussaidene K" first="Kahina" last="Oussaidene">Kahina Oussaidene</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baquet, Georges" sort="Baquet, Georges" uniqKey="Baquet G" first="Georges" last="Baquet">Georges Baquet</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Heyman, Elsa" sort="Heyman, Elsa" uniqKey="Heyman E" first="Elsa" last="Heyman">Elsa Heyman</name>
<affiliation><nlm:aff id="aff1">Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Medicine and Science in Sports and Exercise</title>
<idno type="ISSN">0195-9131</idno>
<idno type="eISSN">1530-0315</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<sec><title>Purpose</title>
<p>Aerobic fitness, as reflected by maximal oxygen (O<sub>2</sub>
) uptake (V˙O<sub>2max</sub>
), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA<sub>1c</sub>
) influence O<sub>2</sub>
 supply including O<sub>2</sub>
 delivery and release to active muscles during maximal exercise.</p>
</sec>
<sec><title>Methods</title>
<p>Two groups of patients with uncomplicated type 1 diabetes (T1D-A, <italic>n</italic>
 = 11, with adequate glycemic control, HbA<sub>1c</sub>
 <7.0%; T1D-I, <italic>n</italic>
 = 12 with inadequate glycemic control, HbA<sub>1c</sub>
 >8%) were compared with healthy controls (CON-A, <italic>n</italic>
 = 11; CON-I, <italic>n</italic>
 = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O<sub>2max</sub>
. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O<sub>2</sub>
 transport and factors able to shift the oxyhemoglobin dissociation curve.</p>
</sec>
<sec><title>Results</title>
<p>Arterial O<sub>2</sub>
 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O<sub>2max</sub>
 was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A.</p>
</sec>
<sec><title>Conclusions</title>
<p>Poorly controlled patients displayed lower V˙O<sub>2max</sub>
 and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O<sub>2</sub>
 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Arturson, G" uniqKey="Arturson G">G Arturson</name>
</author>
<author><name sortKey="Garby, L" uniqKey="Garby L">L Garby</name>
</author>
<author><name sortKey="Robert, M" uniqKey="Robert M">M Robert</name>
</author>
<author><name sortKey="Zaar, B" uniqKey="Zaar B">B Zaar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aspenes, St" uniqKey="Aspenes S">ST Aspenes</name>
</author>
<author><name sortKey="Nilsen, Til" uniqKey="Nilsen T">TIL Nilsen</name>
</author>
<author><name sortKey="Skaug, Ea" uniqKey="Skaug E">EA Skaug</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Astorino, Ta" uniqKey="Astorino T">TA Astorino</name>
</author>
<author><name sortKey="White, Ac" uniqKey="White A">AC White</name>
</author>
<author><name sortKey="Dalleck, Lc" uniqKey="Dalleck L">LC Dalleck</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Astrand, Po" uniqKey="Astrand P">PO Astrand</name>
</author>
<author><name sortKey="Rodahl, K" uniqKey="Rodahl K">K Rodahl</name>
</author>
<author><name sortKey="Dahl, Ha" uniqKey="Dahl H">HA Dahl</name>
</author>
<author><name sortKey="Stromme, Sb" uniqKey="Stromme S">SB Stromme</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Baldi, Jc" uniqKey="Baldi J">JC Baldi</name>
</author>
<author><name sortKey="Cassuto, Na" uniqKey="Cassuto N">NA Cassuto</name>
</author>
<author><name sortKey="Foxx Lupo, Wt" uniqKey="Foxx Lupo W">WT Foxx-Lupo</name>
</author>
<author><name sortKey="Wheatley, Cm" uniqKey="Wheatley C">CM Wheatley</name>
</author>
<author><name sortKey="Snyder, Em" uniqKey="Snyder E">EM Snyder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bassett, Dr" uniqKey="Bassett D">DR Bassett</name>
</author>
<author><name sortKey="Howley, Et" uniqKey="Howley E">ET Howley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bhambhani, Yn" uniqKey="Bhambhani Y">YN Bhambhani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bodnar, Pn" uniqKey="Bodnar P">PN Bodnar</name>
</author>
<author><name sortKey="Pristupiuk, Am" uniqKey="Pristupiuk A">AM Pristupiuk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brazeau, As" uniqKey="Brazeau A">AS Brazeau</name>
</author>
<author><name sortKey="Rabasa Lhoret, R" uniqKey="Rabasa Lhoret R">R Rabasa-Lhoret</name>
</author>
<author><name sortKey="Strychar, I" uniqKey="Strychar I">I Strychar</name>
</author>
<author><name sortKey="Mircescu, H" uniqKey="Mircescu H">H Mircescu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bunn, Hf" uniqKey="Bunn H">HF Bunn</name>
</author>
<author><name sortKey="Briehl, Rw" uniqKey="Briehl R">RW Briehl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chance, Ww" uniqKey="Chance W">WW Chance</name>
</author>
<author><name sortKey="Rhee, C" uniqKey="Rhee C">C Rhee</name>
</author>
<author><name sortKey="Yilmaz, C" uniqKey="Yilmaz C">C Yilmaz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Clark, Mg" uniqKey="Clark M">MG Clark</name>
</author>
<author><name sortKey="Rattigan, S" uniqKey="Rattigan S">S Rattigan</name>
</author>
<author><name sortKey="Clerk, Lh" uniqKey="Clerk L">LH Clerk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Delorey, Ds" uniqKey="Delorey D">DS DeLorey</name>
</author>
<author><name sortKey="Kowalchuk, Jm" uniqKey="Kowalchuk J">JM Kowalchuk</name>
</author>
<author><name sortKey="Paterson, Dh" uniqKey="Paterson D">DH Paterson</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Ditzel, J" uniqKey="Ditzel J">J Ditzel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ditzel, J" uniqKey="Ditzel J">J Ditzel</name>
</author>
<author><name sortKey="Kjaergaard, Jj" uniqKey="Kjaergaard J">JJ Kjaergaard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Esposito, F" uniqKey="Esposito F">F Esposito</name>
</author>
<author><name sortKey="Mathieu Costello, O" uniqKey="Mathieu Costello O">O Mathieu-Costello</name>
</author>
<author><name sortKey="Shabetai, R" uniqKey="Shabetai R">R Shabetai</name>
</author>
<author><name sortKey="Wagner, Pd" uniqKey="Wagner P">PD Wagner</name>
</author>
<author><name sortKey="Richardson, Rs" uniqKey="Richardson R">RS Richardson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ferrari, M" uniqKey="Ferrari M">M Ferrari</name>
</author>
<author><name sortKey="Muthalib, M" uniqKey="Muthalib M">M Muthalib</name>
</author>
<author><name sortKey="Quaresima, V" uniqKey="Quaresima V">V Quaresima</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grassi, B" uniqKey="Grassi B">B Grassi</name>
</author>
<author><name sortKey="Pogliaghi, S" uniqKey="Pogliaghi S">S Pogliaghi</name>
</author>
<author><name sortKey="Rampichini, S" uniqKey="Rampichini S">S Rampichini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jones, Md" uniqKey="Jones M">MD Jones</name>
</author>
<author><name sortKey="Booth, J" uniqKey="Booth J">J Booth</name>
</author>
<author><name sortKey="Taylor, Jl" uniqKey="Taylor J">JL Taylor</name>
</author>
<author><name sortKey="Barry, Bk" uniqKey="Barry B">BK Barry</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Komatsu, Wr" uniqKey="Komatsu W">WR Komatsu</name>
</author>
<author><name sortKey="Barros Neto, Tl" uniqKey="Barros Neto T">TL Barros Neto</name>
</author>
<author><name sortKey="Chacra, Ar" uniqKey="Chacra A">AR Chacra</name>
</author>
<author><name sortKey="Dib, Sa" uniqKey="Dib S">SA Dib</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lakoski, Sg" uniqKey="Lakoski S">SG Lakoski</name>
</author>
<author><name sortKey="Barlow, Ce" uniqKey="Barlow C">CE Barlow</name>
</author>
<author><name sortKey="Farrell, Sw" uniqKey="Farrell S">SW Farrell</name>
</author>
<author><name sortKey="Berry, Jd" uniqKey="Berry J">JD Berry</name>
</author>
<author><name sortKey="Morrow, Jr" uniqKey="Morrow J">JR Morrow</name>
</author>
<author><name sortKey="Haskell, Wl" uniqKey="Haskell W">WL Haskell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Laplaud, D" uniqKey="Laplaud D">D Laplaud</name>
</author>
<author><name sortKey="Hug, F" uniqKey="Hug F">F Hug</name>
</author>
<author><name sortKey="Grelot, L" uniqKey="Grelot L">L Grélot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lukacs, A" uniqKey="Lukacs A">A Lukács</name>
</author>
<author><name sortKey="Mayer, K" uniqKey="Mayer K">K Mayer</name>
</author>
<author><name sortKey="Juhasz, E" uniqKey="Juhasz E">E Juhász</name>
</author>
<author><name sortKey="Varga, B" uniqKey="Varga B">B Varga</name>
</author>
<author><name sortKey="Fodor, B" uniqKey="Fodor B">B Fodor</name>
</author>
<author><name sortKey="Barkai, L" uniqKey="Barkai L">L Barkai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Marschner, Jp" uniqKey="Marschner J">JP Marschner</name>
</author>
<author><name sortKey="Seidlitz, T" uniqKey="Seidlitz T">T Seidlitz</name>
</author>
<author><name sortKey="Rietbrock, N" uniqKey="Rietbrock N">N Rietbrock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcdonald, Mj" uniqKey="Mcdonald M">MJ McDonald</name>
</author>
<author><name sortKey="Bleichman, M" uniqKey="Bleichman M">M Bleichman</name>
</author>
<author><name sortKey="Bunn, Hf" uniqKey="Bunn H">HF Bunn</name>
</author>
<author><name sortKey="Noble, Rw" uniqKey="Noble R">RW Noble</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mollard, P" uniqKey="Mollard P">P Mollard</name>
</author>
<author><name sortKey="Bourdillon, N" uniqKey="Bourdillon N">N Bourdillon</name>
</author>
<author><name sortKey="Letournel, M" uniqKey="Letournel M">M Letournel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nadeau, Kj" uniqKey="Nadeau K">KJ Nadeau</name>
</author>
<author><name sortKey="Regensteiner, Jg" uniqKey="Regensteiner J">JG Regensteiner</name>
</author>
<author><name sortKey="Bauer, Ta" uniqKey="Bauer T">TA Bauer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nielsen, Hb" uniqKey="Nielsen H">HB Nielsen</name>
</author>
<author><name sortKey="Madsen, P" uniqKey="Madsen P">P Madsen</name>
</author>
<author><name sortKey="Svendsen, Lb" uniqKey="Svendsen L">LB Svendsen</name>
</author>
<author><name sortKey="Roach, Rc" uniqKey="Roach R">RC Roach</name>
</author>
<author><name sortKey="Secher, Nh" uniqKey="Secher N">NH Secher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Niranjan, V" uniqKey="Niranjan V">V Niranjan</name>
</author>
<author><name sortKey="Mcbrayer, Dg" uniqKey="Mcbrayer D">DG McBrayer</name>
</author>
<author><name sortKey="Ramirez, Lc" uniqKey="Ramirez L">LC Ramirez</name>
</author>
<author><name sortKey="Raskin, P" uniqKey="Raskin P">P Raskin</name>
</author>
<author><name sortKey="Hsia, Cc" uniqKey="Hsia C">CC Hsia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Padilla, Dj" uniqKey="Padilla D">DJ Padilla</name>
</author>
<author><name sortKey="Mcdonough, P" uniqKey="Mcdonough P">P McDonough</name>
</author>
<author><name sortKey="Behnke, Bj" uniqKey="Behnke B">BJ Behnke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peltonen, Je" uniqKey="Peltonen J">JE Peltonen</name>
</author>
<author><name sortKey="Koponen, As" uniqKey="Koponen A">AS Koponen</name>
</author>
<author><name sortKey="Pullinen, K" uniqKey="Pullinen K">K Pullinen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pichler, G" uniqKey="Pichler G">G Pichler</name>
</author>
<author><name sortKey="Urlesberger, B" uniqKey="Urlesberger B">B Urlesberger</name>
</author>
<author><name sortKey="Jirak, P" uniqKey="Jirak P">P Jirak</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Plasqui, G" uniqKey="Plasqui G">G Plasqui</name>
</author>
<author><name sortKey="Westerterp, Kr" uniqKey="Westerterp K">KR Westerterp</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Poortmans, Jr" uniqKey="Poortmans J">JR Poortmans</name>
</author>
<author><name sortKey="Saerens, P" uniqKey="Saerens P">P Saerens</name>
</author>
<author><name sortKey="Edelman, R" uniqKey="Edelman R">R Edelman</name>
</author>
<author><name sortKey="Vertongen, F" uniqKey="Vertongen F">F Vertongen</name>
</author>
<author><name sortKey="Dorchy, H" uniqKey="Dorchy H">H Dorchy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roberts, Ap" uniqKey="Roberts A">AP Roberts</name>
</author>
<author><name sortKey="Story, Cj" uniqKey="Story C">CJ Story</name>
</author>
<author><name sortKey="Ryall, Rg" uniqKey="Ryall R">RG Ryall</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roca, J" uniqKey="Roca J">J Roca</name>
</author>
<author><name sortKey="Agusti, Ag" uniqKey="Agusti A">AG Agusti</name>
</author>
<author><name sortKey="Alonso, A" uniqKey="Alonso A">A Alonso</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wanke, T" uniqKey="Wanke T">T Wanke</name>
</author>
<author><name sortKey="Formanek, D" uniqKey="Formanek D">D Formanek</name>
</author>
<author><name sortKey="Auinger, M" uniqKey="Auinger M">M Auinger</name>
</author>
<author><name sortKey="Zwick, H" uniqKey="Zwick H">H Zwick</name>
</author>
<author><name sortKey="Irsigler, K" uniqKey="Irsigler K">K Irsigler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wheatley, Cm" uniqKey="Wheatley C">CM Wheatley</name>
</author>
<author><name sortKey="Baldi, Jc" uniqKey="Baldi J">JC Baldi</name>
</author>
<author><name sortKey="Cassuto, Na" uniqKey="Cassuto N">NA Cassuto</name>
</author>
<author><name sortKey="Foxx Lupo, Wt" uniqKey="Foxx Lupo W">WT Foxx-Lupo</name>
</author>
<author><name sortKey="Snyder, Em" uniqKey="Snyder E">EM Snyder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Whipp, Bj" uniqKey="Whipp B">BJ Whipp</name>
</author>
<author><name sortKey="Higgenbotham, Mb" uniqKey="Higgenbotham M">MB Higgenbotham</name>
</author>
<author><name sortKey="Cobb, Fc" uniqKey="Cobb F">FC Cobb</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Womack, L" uniqKey="Womack L">L Womack</name>
</author>
<author><name sortKey="Peters, D" uniqKey="Peters D">D Peters</name>
</author>
<author><name sortKey="Barrett, Ej" uniqKey="Barrett E">EJ Barrett</name>
</author>
<author><name sortKey="Kaul, S" uniqKey="Kaul S">S Kaul</name>
</author>
<author><name sortKey="Price, W" uniqKey="Price W">W Price</name>
</author>
<author><name sortKey="Lindner, Jr" uniqKey="Lindner J">JR Lindner</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Med Sci Sports Exerc</journal-id>
<journal-id journal-id-type="iso-abbrev">Med Sci Sports Exerc</journal-id>
<journal-id journal-id-type="publisher-id">MSS</journal-id>
<journal-title-group><journal-title>Medicine and Science in Sports and Exercise</journal-title>
</journal-title-group>
<issn pub-type="ppub">0195-9131</issn>
<issn pub-type="epub">1530-0315</issn>
<publisher><publisher-name>Lippincott Williams & Wilkins</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24983346</article-id>
<article-id pub-id-type="pmc">4323553</article-id>
<article-id pub-id-type="publisher-id">MSS14440</article-id>
<article-id pub-id-type="doi">10.1249/MSS.0000000000000424</article-id>
<article-id pub-id-type="art-access-id">00002</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Clinical Sciences</subject>
</subj-group>
</article-categories>
<title-group><article-title>Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>TAGOUGUI</surname>
<given-names>SEMAH</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>LECLAIR</surname>
<given-names>ERWAN</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1,2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>FONTAINE</surname>
<given-names>PIERRE</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>MATRAN</surname>
<given-names>RÉGIS</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>MARAIS</surname>
<given-names>GAELLE</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>AUCOUTURIER</surname>
<given-names>JULIEN</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>DESCATOIRE</surname>
<given-names>AURÉLIEN</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>VAMBERGUE</surname>
<given-names>ANNE</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>OUSSAIDENE</surname>
<given-names>KAHINA</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>BAQUET</surname>
<given-names>GEORGES</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>HEYMAN</surname>
<given-names>ELSA</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup>
Physical Activity, Muscle and Health, Lille, EA 4488, University of Lille 2, FRANCE;<sup>2</sup>
Department of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, CANADA;<sup>3</sup>
Department of Diabetology, Lille University Hospital, EA 4489, Lille, FRANCE;<sup>4</sup>
Department of Physiology, EA 2689 and IFR 22, Lille, FRANCE; and<sup>5</sup>
Regional Hospital Centre of Roubaix, FRANCE</aff>
<author-notes><corresp>Address for correspondence: Elsa Heyman, Ph.D., Physical Activity, Muscle and Health, EA 4488, Faculté des Sciences du Sport et de l’Education Physique, 9 rue de l’Université 59790 Ronchin, France; E-mail: 
<email>elsa.heyman@univ-lille2.fr</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>2</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>16</day>
<month>1</month>
<year>2015</year>
</pub-date>
<volume>47</volume>
<issue>2</issue>
<fpage>231</fpage>
<lpage>239</lpage>
<history><date date-type="received"><month>5</month>
<year>2014</year>
</date>
<date date-type="accepted"><month>6</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2015 by the American College of Sports Medicine</copyright-statement>
<copyright-year>2015</copyright-year>
<license><license-p>This is an open-access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:type="simple" xlink:href="mss-47-231.pdf"></self-uri>
<abstract><title>ABSTRACT</title>
<sec><title>Purpose</title>
<p>Aerobic fitness, as reflected by maximal oxygen (O<sub>2</sub>
) uptake (V˙O<sub>2max</sub>
), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA<sub>1c</sub>
) influence O<sub>2</sub>
 supply including O<sub>2</sub>
 delivery and release to active muscles during maximal exercise.</p>
</sec>
<sec><title>Methods</title>
<p>Two groups of patients with uncomplicated type 1 diabetes (T1D-A, <italic>n</italic>
 = 11, with adequate glycemic control, HbA<sub>1c</sub>
 <7.0%; T1D-I, <italic>n</italic>
 = 12 with inadequate glycemic control, HbA<sub>1c</sub>
 >8%) were compared with healthy controls (CON-A, <italic>n</italic>
 = 11; CON-I, <italic>n</italic>
 = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O<sub>2max</sub>
. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O<sub>2</sub>
 transport and factors able to shift the oxyhemoglobin dissociation curve.</p>
</sec>
<sec><title>Results</title>
<p>Arterial O<sub>2</sub>
 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O<sub>2max</sub>
 was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A.</p>
</sec>
<sec><title>Conclusions</title>
<p>Poorly controlled patients displayed lower V˙O<sub>2max</sub>
 and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O<sub>2</sub>
 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy.</p>
</sec>
</abstract>
<kwd-group><title>Key Words</title>
<kwd>AEROBIC FITNESS</kwd>
<kwd>GLYCATED HEMOGLOBIN</kwd>
<kwd>OXYGEN DELIVERY</kwd>
<kwd>OXYGEN RELEASE</kwd>
<kwd>SKELETAL MUSCLE</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>OPEN-ACCESS</meta-name>
<meta-value>TRUE</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body><p>The beneficial effects of physical activity and the advantages of good physical fitness are well established both in healthy individuals and in those with chronic disease (<xref rid="R20" ref-type="bibr">20</xref>
,<xref rid="R21" ref-type="bibr">21</xref>
). Aerobic fitness, as measured by maximal oxygen (O<sub>2</sub>
) uptake (V˙O<sub>2max</sub>
), is a strong predictor of cardiovascular risk (<xref rid="R2" ref-type="bibr">2</xref>
). In patients with type 1 diabetes, poor fitness represents an important barrier to regular physical activity (<xref rid="R9" ref-type="bibr">9</xref>
). Consequently, better understanding of the underlying factors involved in the possible impairment of V˙O<sub>2max</sub>
 in patients with type 1 diabetes is warranted.</p>
<p>Low aerobic fitness levels have been reported in several (<xref rid="R28" ref-type="bibr">28</xref>
,<xref rid="R32" ref-type="bibr">32</xref>
), albeit not all (<xref rid="R21" ref-type="bibr">21</xref>
,<xref rid="R39" ref-type="bibr">39</xref>
), studies in adults with type 1 diabetes and seem to be associated with poor glycemic control, as reflected by high glycated hemoglobin (HbA<sub>1c</sub>
) levels (<xref rid="R5" ref-type="bibr">5</xref>
,<xref rid="R24" ref-type="bibr">24</xref>
,<xref rid="R30" ref-type="bibr">30</xref>
). A high HbA<sub>1c</sub>
 level is indeed an important factor in the initiation and progression of micro- and macrovascular complications. In turn, these complications may alter the functioning of tissues that are important for exercise adaptations, such as blood vessels, lungs, and heart (<xref rid="R11" ref-type="bibr">11</xref>
,<xref rid="R41" ref-type="bibr">41</xref>
) and, consequently, reduce V˙O<sub>2max</sub>
.</p>
<p>However, there may be other factors involved in the impairment of aerobic fitness observed in individuals with poor glycemic control. In this respect, the HbA<sub>1c</sub>
– V˙O<sub>2max</sub>
 relation has been found even in the absence of diabetic complications in young patients with type 1 diabetes (<xref rid="R24" ref-type="bibr">24</xref>
,<xref rid="R35" ref-type="bibr">35</xref>
). O<sub>2</sub>
 supply, including arterial O<sub>2</sub>
 delivery and O<sub>2</sub>
 release (i.e., oxyhemoglobin (O<sub>2</sub>
Hb) dissociation) to active muscles, is a well-established factor influencing V˙O<sub>2max</sub>
 in healthy subjects or subjects with a chronic disease (<xref rid="R17" ref-type="bibr">17</xref>
,<xref rid="R29" ref-type="bibr">29</xref>
). In adolescents with type 1 diabetes, one study reported reduction in forearm blood flow after local exercise (rhythmic handgrip) despite the absence of any otherwise clinically detectable vascular disorders (<xref rid="R33" ref-type="bibr">33</xref>
). To our knowledge, arterial O<sub>2</sub>
 transport capacity has never been investigated during exercise in patients with type 1 diabetes and with different levels of HbA<sub>1c</sub>
.</p>
<p>Several <italic>in vitro</italic>
 studies suggest possibly increased O<sub>2</sub>
Hb affinity (i.e., a leftward shift of the O<sub>2</sub>
 dissociation curve) and/or decreased sensitivity of hemoglobin to the allosteric effect of organic phosphates as a result of hemoglobin glycation at a degree corresponding to HbA<sub>1c</sub>
 levels in patients with poor glycemic control (i.e., 8%) (<xref rid="R10" ref-type="bibr">10</xref>
,<xref rid="R25" ref-type="bibr">25</xref>
,<xref rid="R26" ref-type="bibr">26</xref>
,<xref rid="R36" ref-type="bibr">36</xref>
). Some further insight into muscle O<sub>2</sub>
Hb dissociation in type 1 diabetes is required, particularly <italic>in vivo</italic>
 during maximal exercise and in accordance with HbA<sub>1c</sub>
 levels. In this respect, near-infrared spectroscopy (NIRS) allows noninvasive and functional monitoring of changes in skeletal muscle oxygenation including O<sub>2</sub>
Hb dissociation (<xref rid="R18" ref-type="bibr">18</xref>
). Besides hemoglobin glycation, it is important to take into account the erythrocyte 2,3-diphosphoglycerate (2,3-DPG) level. This stimulus for a rightward shift of the O<sub>2</sub>
Hb dissociation curve has been found to be, contradictorily, either reduced (<xref rid="R15" ref-type="bibr">15</xref>
,<xref rid="R16" ref-type="bibr">16</xref>
) or elevated in patients with type 1 diabetes (<xref rid="R8" ref-type="bibr">8</xref>
), especially in cases of chronically impaired glycemic control (<xref rid="R1" ref-type="bibr">1</xref>
).</p>
<p>Therefore, we aimed to determine whether O<sub>2</sub>
 delivery and/or release to an active muscle during maximal exercise is altered in patients with uncomplicated type 1 diabetes and high levels of HbA<sub>1c</sub>
 and whether any subsequent relation to impairment in V˙O<sub>2max</sub>
 exists.</p>
<sec sec-type="materials|methods"><title>MATERIAL AND METHODS</title>
<p>A written informed consent was obtained from all participants before their inclusion in this study, which was approved by the North Western IV regional ethics committee (N° EudraCT, 2009-A00746-51). Twenty-three patients, age 18–40 yr, who had type 1 diabetes for at least 1 yr and were free from vascular complications, volunteered to participate in this study (Table <xref ref-type="table" rid="T1">1</xref>
). The absence of microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (high blood pressure, coronary disease, peripheral arteriopathy) complications was carefully checked by a clinician during the initial examination. The patients were then divided into two groups according to their HbA<sub>1c</sub>
 levels measured at inclusion, as follows: adequate glycemic control, T1D-A (<italic>n</italic>
 = 11; HbA<sub>1c</sub>
 <7% (53 mmol·mol<sup>−1</sup>
)); and inadequate glycemic control, T1D-I (<italic>n</italic>
 = 12; HbA<sub>1c</sub>
 >8% (64 mmol·mol<sup>−1</sup>
)). Two control groups, CON-A and CON-I, composed of healthy subjects age 18–40 yr, were recruited (as described in the following section) to strictly match the T1D-A and T1D-I groups, respectively.</p>
<table-wrap id="T1" position="float"><label>TABLE 1</label>
<caption><p>Participants’ characteristics.</p>
</caption>
<graphic xlink:href="mss-47-231-g001"></graphic>
</table-wrap>
<sec><title></title>
<sec><title>Selection process of the healthy control subjects.</title>
<p>Healthy participants were selected from a list (<italic>n</italic>
 = 250) drawn from patients’ friends and contacts. Each healthy control was chosen to strictly match a patient with type 1 diabetes according to the following preestablished ranges or values: gender, same as the case patient; age, ±7 yr; body mass index, ±4 kg·m<sup>−2</sup>
; moderate-to-vigorous physical activity levels, ±1 h when the patients’ physical activity category was 0 h·wk<sup>−1</sup>
, ±2 h for category 2–6 h·wk<sup>−1</sup>
, ±4 h for category >6 h·wk<sup>−1</sup>
, pairs of patient/control being in the same category, and tobacco status, grouped according to no smoking, <10 cigarettes a day, and >10 cigarettes a day. The healthy controls chosen were then recruited after an oral glucose tolerance test (75 g). Individuals were excluded if they had a fasting blood glucose level of >6.05 mM or an abnormal glucose tolerance test result using World Health Organization criteria (<xref rid="R14" ref-type="bibr">14</xref>
). The similarity of body composition and physical activity levels between groups was then accurately checked using dual energy x-ray absorptiometry (Hologic, Inc., Waltham, MA) and accelerometry (ActiGraph, model GT1M) over seven consecutive days, respectively (Table <xref ref-type="table" rid="T1">1</xref>
).</p>
<p>Besides physical activity levels, we added an assessment of lifestyle diet. Dietary data were based on a 3-d diary (based on two weekdays and one weekend day). Written instructions were given to provide detailed information about the quantity and quality of all items consumed. The patients were then interviewed by a research-trained dietitian, who gathered information to supplement the diaries.</p>
</sec>
<sec><title>Laboratory testing.</title>
<p>Subjects were requested to refrain from vigorous physical activity for 48 h before the test and from using tobacco in the morning of the test. Patients with type 1 diabetes received their usual morning insulin bolus, and all subjects consumed a breakfast (providing 8.5% ± 3.4% proteins, 41.4% ± 16.4% lipids, and 50.1% ± 15.8% CHO) based on their usual breakfast and previously agreed upon by a dietician. The exercise test began 3.8 ± 0.6 h after breakfast. After a 2-min resting period sitting on the cycle ergometer (Excalibur Sport; Lode BV, Groningen, Netherlands), the test started at 30 W and continued with a 20-W increment every 2 min until exhaustion.</p>
</sec>
<sec><title>Cardiopulmonary response.</title>
<p>An ECG (Ergocard®; Medisoft, Dinant, Belgium) was performed at rest and continually monitored throughout the exercise test by a cardiologist.</p>
<p>Pulmonary gas exchanges were measured continuously throughout exercise (breath-by-breath system, Ergocard®). V˙O<sub>2max</sub>
 was determined as the highest 15-s average value during the exercise test. Validation of V˙O<sub>2max</sub>
 was obtained at the termination of the test when three of the following five criteria were attained: 1) V˙O<sub>2</sub>
 increase of <100 mL·min<sup>−1</sup>
 with the 20-W increase in power output, 2) an HR >90% of the theoretical HR<sub>max</sub>
 (210 − 0.65 × age), 3) an RPE score ≥19, 4) blood lactate >8 mM, and 5) an RER >1.1 (<xref rid="R4" ref-type="bibr">4</xref>
). According to these criteria, all subjects achieved their V˙O<sub>2max</sub>
 (Table <xref ref-type="table" rid="T2">2</xref>
).</p>
<table-wrap id="T2" position="float"><label>TABLE 2</label>
<caption><p>Cardiopulmonary and metabolic data from participants during incremental maximal exercise.</p>
</caption>
<graphic xlink:href="mss-47-231-g002"></graphic>
</table-wrap>
<p>The O<sub>2</sub>
 pulse (mL·beat<sup>−1</sup>
) was calculated as the ratio between O<sub>2</sub>
 consumption and HR and was used as an indicator of stroke volume during submaximal and maximal exercise (<xref rid="R40" ref-type="bibr">40</xref>
).</p>
</sec>
<sec><title>NIRS measurements.</title>
<p>Subjects were equipped with an NIRS probe to monitor the absorption of light across muscle tissues throughout the exercise test (Oxymon Mk III; Artinis Medical Systems, Zetten, The Netherlands). The emitter-and-detector pair was placed on the belly of the right vastus lateralis muscle, midway between the lateral epicondyle and greater trochanter of the femur. The vastus lateralis muscle is highly active during cycling (<xref rid="R23" ref-type="bibr">23</xref>
), making it suitable for examining exercise-induced changes in active muscle oxygenation. Adipose tissue thickness has been reported to have substantial confounding influence on <italic>in vivo</italic>
 NIRS measurements (<xref rid="R18" ref-type="bibr">18</xref>
). Therefore, we ensured that the vastus lateralis skinfold was <1.5 cm and that fat mass percentage in the right leg was comparable between groups (Table <xref ref-type="table" rid="T1">1</xref>
). The interoptode distance was 40 mm. NIRS data were collected with a sampling frequency of 10 Hz.</p>
<p>The Beer–Lambert law was used to calculate changes in tissue oxygenation O<sub>2</sub>
Hb (ΔO<sub>2</sub>
Hb) and deoxyhemoglobin (ΔHHb) across time using optical densities from two continuous wavelengths of NIR light (780 and 850 nm). The change in total hemoglobin (ΔTHb), i.e., the arithmetic sum of ΔO<sub>2</sub>
Hb and ΔHHb, was used as an index of change in regional blood volume (<xref rid="R19" ref-type="bibr">19</xref>
). ΔHHb was used as a sensitive reflection of relative tissue deoxygenation due to O<sub>2</sub>
 extraction because this measure is closely associated with changes in venous O<sub>2</sub>
 content and is less sensitive to ΔTHb than ΔO<sub>2</sub>
Hb (<xref rid="R19" ref-type="bibr">19</xref>
). NIRS measurements were normalized to reflect changes from the 1-min baseline period immediately before beginning the exercise protocol (arbitrarily defined as 0 μM) to express the magnitudes of changes throughout exercise.</p>
<p>The use and limitations of NIRS have been extensively reviewed (<xref rid="R7" ref-type="bibr">7</xref>
,<xref rid="R18" ref-type="bibr">18</xref>
). Noteworthy, the NIRS technique is unable to differentiate between the amount of O<sub>2</sub>
 released by both hemoglobin and myoglobin because the absorbency signals of these two chromophores overlap in the NIR range. On the basis of data available on hemoglobin/myoglobin ratio in human muscles, one can estimate that myoglobin represents a confounding factor of 10% of the whole hemoglobin signal (<xref rid="R18" ref-type="bibr">18</xref>
). Consequently, it can be assumed that most of the NIRS signal reflects changes in absorption of ΔO<sub>2</sub>
Hb and ΔHHb (<xref rid="R18" ref-type="bibr">18</xref>
).</p>
</sec>
<sec><title>Blood analyses.</title>
<p>Venous blood samples were collected from a forearm catheter at rest and at maximal exercise. HbA<sub>1c</sub>
 was measured at rest from EDTA blood (HPLC assay, VARIANT<sup>2</sup>
 Turbo; Bio-Rad) (Table <xref ref-type="table" rid="T1">1</xref>
). At rest and maximal exercise, fluorinated and heparinized samples were used to analyze blood glucose (hexokinase enzymatic assay, Modular automat) and erythrocyte 2,3-DPG (spectrophotometry; Sigma-Aldrich, St. Louis, MO), respectively.</p>
<p>At rest and immediately at exhaustion, a microcapillary arterialized earlobe blood sample (vasodilator pomade applied 5 min before sampling) was collected to analyze lactate (amperometry, on ABL800 radiometer), factors able to modify the O<sub>2</sub>
Hb dissociation curve (pH, partial pressure of carbon dioxide (PaCO<sub>2</sub>
), by potentiometry, on ABL800 radiometer), and components of arterial O<sub>2</sub>
 content (CaO<sub>2</sub>
) (<xref rid="R27" ref-type="bibr">27</xref>
) (arterial O<sub>2</sub>
 saturation (SaO<sub>2</sub>
) by spectrophotometry, partial pressure of O<sub>2</sub>
 (PaO<sub>2</sub>
) by amperometry, hemoglobin concentration by spectrophotometry, on ABL800 Radiometer). CaO<sub>2</sub>
 was calculated as the sum of bound (1.39 (hemoglobin) × SaO<sub>2</sub>
) and dissolved O<sub>2</sub>
 (0.003 PaO<sub>2</sub>
).</p>
</sec>
<sec><title>Statistical analyses.</title>
<p>Statistics were computed using SAS 9.3 (SAS Institute, Inc., Cary, NC). Results are reported as means ± SD unless otherwise indicated. Normality was tested using the Shapiro–Wilk test. Demographic, anthropometric, and aerobic fitness data were compared between patients with type 1 diabetes and their respective group of healthy controls using the Wilcoxon matched-pairs test. NIRS data, arterialized O<sub>2</sub>
 transport, and blood factors able to influence the O<sub>2</sub>
Hb dissociation curve were compared between patients with type 1 diabetes and their respective control group using a linear mixed model for repeated measurements. In this model, the fixed effects were the group effect (i.e., T1D-A vs CON-A and T1D-I vs CON-I), the exercise effect (repeated measurements corresponding to relative intensity levels—10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% of V˙O<sub>2max</sub>
)—and the group–exercise interaction. The mixed model is an extension of the classical ANOVA allowing handling of correlations between repeated measurements. The choice of the covariance pattern model was based on the Akaike information criterion. The influence of each individual on the results was investigated using the Cook distance. If significant main effects or an interaction was observed with ANOVA, Bonferroni <italic>post hoc</italic>
 pairwise comparisons were applied. Pearson correlation coefficients were used to detect correlations between two continuous parametric variables. <italic>P</italic>
 < 0.05 was considered statistically significant.</p>
</sec>
</sec>
</sec>
<sec sec-type="results"><title>RESULTS</title>
<sec><title></title>
<sec><title>Subjects’ characteristics.</title>
<p>Demographic and physical activity data from patients with type 1 diabetes and their matched healthy controls are summarized in Table <xref ref-type="table" rid="T1">1</xref>
. On the day of the exercise test, HbA<sub>1c</sub>
 levels ranged between 8% and 10.3% in T1D-I and between 5.5% and 7.5% in T1D-A. The latter is explained by the fact that, for four of the 11 patients in the T1D-A group, HbA<sub>1c</sub>
 changed from levels <7.0% the day of inclusion to levels between 7.0% and 7.5% on the day of exercise test. Plasma glucose concentrations increased during exercise in all groups (Table <xref ref-type="table" rid="T2">2</xref>
). None of the patients with type 1 diabetes became hypoglycemic during exercise.</p>
</sec>
<sec><title>V˙O<sub>2max</sub>
.</title>
<p>T1D-I had lower V˙O<sub>2max</sub>
 than CON-I despite comparable levels of habitual physical activity (Table <xref ref-type="table" rid="T1">1</xref>
) as well as comparable HR achieved at exhaustion (Table <xref ref-type="table" rid="T2">2</xref>
). No significant difference in V˙O<sub>2max</sub>
 was observed between T1D-A and CON-A (Table <xref ref-type="table" rid="T2">2</xref>
).</p>
</sec>
<sec><title>Arterial O<sub>2</sub>
 transport.</title>
<p>CaO<sub>2</sub>
, and its components ([hemoglobin], SaO<sub>2</sub>
, PaO<sub>2</sub>
), did not differ significantly between T1D-I and CON-I during the exercise test. T1D-A had higher CaO<sub>2</sub>
 compared with CON-A, which could be explained by higher hemoglobin concentration. Levels and exercise-induced changes in PaO<sub>2</sub>
, SaO<sub>2</sub>
, and O<sub>2</sub>
 pulse were not significantly different between the groups (Table <xref ref-type="table" rid="T2">2</xref>
).</p>
</sec>
<sec><title>Muscle oxygenation and deoxygenation profiles.</title>
<p>ΔTHb was significantly lower in T1D-I compared with that in CON-I during exercise, whereas no significant difference were observed between T1D-A and CON-A (Fig. <xref ref-type="fig" rid="F1">1</xref>
 and Table <xref ref-type="table" rid="T3">3</xref>
).</p>
<table-wrap id="T3" position="float"><label>TABLE 3</label>
<caption><p>Main effects by ANOVA regarding results from NIRS.</p>
</caption>
<graphic xlink:href="mss-47-231-g003"></graphic>
</table-wrap>
<fig id="F1" position="float"><label>FIGURE 1</label>
<caption><p>Recordings made by NIRS from the vastus lateralis. Change in ΔTHb (A and B), change in ΔO2Hb (C and D), and change in ΔHHb (E and F). Values are means ± SE. T1D-I, <italic>black squares</italic>
; CON-I, <italic>white squares</italic>
; T1D-A, <italic>black triangles</italic>
; CON-A, <italic>white triangles</italic>
. <italic>Post hoc</italic>
 analyses for group effect: significantly different from controls at *<italic>P</italic>
 < 0.05 and ***<italic>P</italic>
 < 0.01. <italic>Post hoc</italic>
 analyses for time effect: significantly different from rest at †<italic>P</italic>
 <0.05, ††<italic>P</italic>
 < 0.01, and †††<italic>P</italic>
 < 0.001.</p>
</caption>
<graphic xlink:href="mss-47-231-g004"></graphic>
</fig>
<p>ΔO<sub>2</sub>
Hb decreased significantly less with exercise intensity in T1D-I compared with that in CON-I, whereas no intergroup differences were observed between T1D-A and CON-A (Fig. <xref ref-type="fig" rid="F1">1</xref>
 and Table <xref ref-type="table" rid="T3">3</xref>
).</p>
<p>ΔHHb increased significantly in T1D-I, T1D-A, CON-I, and CON-A throughout the exercise test (Fig. <xref ref-type="fig" rid="F1">1</xref>
 and Table <xref ref-type="table" rid="T3">3</xref>
). However, the levels of ΔHHb and the increase in ΔHHb were lower in T1D-I compared with those in CON-I (Table <xref ref-type="table" rid="T3">3</xref>
), particularly at exercise intensities above 60% of V˙O<sub>2max</sub>
 (Fig. <xref ref-type="fig" rid="F1">1</xref>
). In contrast, there were no differences in ΔHHb levels and changes between T1D-A and CON-A (Table <xref ref-type="table" rid="T3">3</xref>
).</p>
</sec>
<sec><title>Factors able to shift the O<sub>2</sub>
Hb dissociation curve.</title>
<p>HbA<sub>1c</sub>
 concentrations were significantly higher in T1D-I compared with those in both CON-I and T1D-A (Table <xref ref-type="table" rid="T1">1</xref>
).</p>
<p>There were no differences in erythrocyte 2,3-DPG levels and pH during exercise between patients with type 1 diabetes and their respective control groups (Table <xref ref-type="table" rid="T2">2</xref>
). PaCO<sub>2</sub>
 was higher in T1D-I compared with that in CON-I (Table <xref ref-type="table" rid="T2">2</xref>
).</p>
<p>In all the previous results sections, we found the same results when females were excluded from statistical analyses. In addition, the use of absolute work rates instead of relative intensity levels for the exercise effect in the mixed models did not change the results’ sense (Table <xref ref-type="table" rid="T3">3</xref>
).</p>
</sec>
</sec>
</sec>
<sec sec-type="discussion"><title>DISCUSSION</title>
<p>We found that patients with inadequate glycemic control but without any clinically detectable vascular complications displayed impaired aerobic capacity as well as reduction in blood volume and dramatic impairment in HHb increase in active skeletal muscles during intense exercise. However, regardless of their HbA<sub>1c</sub>
 levels, patients with type 1 diabetes had adequate CaO<sub>2</sub>
. These results seem all the more relevant, given that this is the first <italic>in vivo</italic>
 study to assess all steps from O<sub>2</sub>
 delivery to release in the skeletal muscle during maximal exercise in patients with type 1 diabetes. In addition, the patients were divided into two groups having distinct levels of HbA<sub>1c</sub>
 and all were free from clinical micro- and macroangiopathy. Another noteworthy feature of this study lies in the care taken to closely match each patient with a healthy control, taking into account the usual demographic data as well as the exact levels of physical activity (7-d accelerometry) (<xref rid="R34" ref-type="bibr">34</xref>
). Regular physical activity is one of the major determinants of V˙O<sub>2max</sub>
 (<xref rid="R21" ref-type="bibr">21</xref>
,<xref rid="R22" ref-type="bibr">22</xref>
) and thus could explain some discrepancies regarding aerobic fitness and type 1 diabetes reported in previous literature.</p>
<sec><title></title>
<sec><title>Aerobic fitness.</title>
<p>Despite being relatively physically active (average of 41.3 ± 23.4 min of moderate to vigorous activities per day), the poorly controlled patients included in our study displayed a level of aerobic fitness (V˙O<sub>2max</sub>
 = 34.6 ± 7.2 mL·kg<sup>−1</sup>
·min<sup>−1</sup>
) corresponding to levels usually observed in sedentary subjects (<xref rid="R3" ref-type="bibr">3</xref>
), suggesting increased risk for cardiovascular diseases (<xref rid="R2" ref-type="bibr">2</xref>
). In our study, the lower aerobic fitness in poorly controlled patients with type 1 diabetes compared with healthy controls is consistent with several studies in the literature (<xref rid="R5" ref-type="bibr">5</xref>
,<xref rid="R30" ref-type="bibr">30</xref>
), in which some patients undoubtedly suffered from micro- and macrovascular complications (<xref rid="R30" ref-type="bibr">30</xref>
). Thus, besides the indirect effect of HbA<sub>1c</sub>
 on aerobic fitness through the presence of chronic hyperglycemia-induced complications, our results raise the possibility of a direct effect of HbA<sub>1c</sub>
 levels on V˙O<sub>2max</sub>
. The mechanisms underlying this direct relation may involve muscle O<sub>2</sub>
 delivery (including arterial O<sub>2</sub>
 transport and muscle blood perfusion) and/or O<sub>2</sub>
 release to muscles, which are two main determinants of V˙O<sub>2max</sub>
 (<xref rid="R6" ref-type="bibr">6</xref>
,<xref rid="R37" ref-type="bibr">37</xref>
).</p>
</sec>
<sec><title>Arterial O<sub>2</sub>
 transport.</title>
<p>Arterial O<sub>2</sub>
 transport is dependent on two key factors. The first is the ability of the lungs to oxygenate the blood as it passes through the pulmonary capillary network. In the current study, this was reflected by the O<sub>2</sub>
 content of arterialized blood (<xref rid="R27" ref-type="bibr">27</xref>
). O<sub>2</sub>
 transport also depends on cardiac output, which is determined by the product of stroke volume (as reflected by O<sub>2</sub>
 pulse) and HR. We observed that arterial O<sub>2</sub>
 transport capacity was comparable in poorly controlled patients with type 1 diabetes and their healthy controls. This finding suggests that, in patients with type 1 diabetes but free from clinically detectable microangiopathy, the increase in pulmonary capillary blood flow and alveolar–capillary diffusion induced by high-intensity exercise does not highlight any limitation in lung function. In agreement with our results, Wanke et al. (<xref rid="R38" ref-type="bibr">38</xref>
) showed that patients with type 1 diabetes, in the absence of overt pulmonary disease, have a normal alveolar–arterial O<sub>2</sub>
 gradient at comparable power outputs.</p>
</sec>
<sec><title>Blood volume in active skeletal muscles.</title>
<p>Changes in THb are thought to reflect changes in tissue blood volume (<xref rid="R19" ref-type="bibr">19</xref>
). Therefore, the significant increase in ΔTHb in both groups of healthy controls and of patients with adequate glycemic control in the present study is consistent with the increase in muscle blood volume usually observed with increasing exercise intensity (<xref rid="R7" ref-type="bibr">7</xref>
). However, in cases of inadequate glycemic control, patients with type 1 diabetes had significantly lower ΔTHb than their healthy controls. Our results supplement those of Pichler et al. (<xref rid="R33" ref-type="bibr">33</xref>
). In children and adolescents with type 1 diabetes, among whom some were poorly controlled (mean HbA<sub>1c</sub>
, 9.2% ± 1.8%), the authors found lower ΔTHb at the forearm muscle in response to a short submaximal local exercise (1-min rhythmic handgrip) performed in addition to provoked nonphysiological increase in forearm arterial inflow. The latter was artificially set up using brachial venous occlusion (three occlusions of 20 s interspaced by a rest period of 40 s). The current study suggests that, even without a preconditioning stress such as venous occlusion, the physiological condition of maximal exercise was sufficient to induce alteration in muscle perfusion. This alteration is possibly favored by endothelial dysfunction and/or functional alterations of the microcirculation occurring even before overt microvascular complications in cases of chronic hyperglycemia (i.e., high HbA<sub>1c</sub>
 levels) and/or in cases of long-term diabetes. The poorly controlled patients, indeed, had longer duration of disease than the well-controlled patients in our study.</p>
</sec>
<sec><title>The exercise-induced HHb increase in active muscles.</title>
<p>There were no differences in ΔHHb levels and its increase between patients with adequate glycemic control and their healthy controls. These results coincide with those of Peltonen et al. (<xref rid="R32" ref-type="bibr">32</xref>
), who reported a comparable level of ΔHHb at maximal exercise in patients with type 1 diabetes with an HbA<sub>1c</sub>
 of 7.7% ± 0.7% and healthy subjects. We did, however, find that patients with inadequate glycemic control displayed dramatic impairment in exercise-induced ΔHHb increase and reduced ΔHHb levels, especially with intense exercise (>60% V˙O<sub>2max</sub>
).</p>
<p>During a bout of exercise, several factors may explain the reduction in ΔHHb increase. First, a lower ΔHHb may be observed in the case of better matching between muscle O<sub>2</sub>
 delivery (particularly depending on CaO<sub>2</sub>
 and muscle blood perfusion) and muscle O<sub>2</sub>
 use. For example, this scenario is seen at the onset of heavy-intensity exercise in young healthy adults compared with older healthy adults because the former displays better increase in muscle blood volume (as reflected by ΔTHb) for a comparable need for O<sub>2</sub>
 for muscle contraction (<xref rid="R13" ref-type="bibr">13</xref>
). However, this mechanism does not explain the ΔHHb impairment in our poorly controlled patients with type 1 diabetes, as they otherwise displayed lower ΔTHb rates during the exercise test.</p>
<p>Secondly, the lower ΔHHb may be explained by lower muscle O<sub>2</sub>
 extraction (<xref rid="R19" ref-type="bibr">19</xref>
). This could occur in two situations, as follows: 1) reduced capacity of O<sub>2</sub>
Hb dissociation, which can occur in pathological circumstances (e.g., CO intoxication) or in sport (e.g., hyperventilation-induced alkalosis in mountaineering), and 2) reduced tissue capacity of O<sub>2</sub>
 use (e.g., mitochondrial dysfunction). The hypothesis of the former situation (i.e., a disturbed O<sub>2</sub>
Hb dissociation rate) is probably involved in the lower exercise level of ΔHHb found <italic>in vivo</italic>
 in our poorly controlled (HbA<sub>1c</sub>
, >8%) patients. Indeed, it has been shown <italic>in vitro</italic>
 that glycation of hemoglobin, at percentages that might be found in patients with diabetes (i.e., 8% HbA<sub>1c</sub>
), reduced the kinetics of hemoglobin O<sub>2</sub>
 release by 10% in comparison with a 4% HbA<sub>1c</sub>
 level (<xref rid="R25" ref-type="bibr">25</xref>
). In our study, the possibility of higher O<sub>2</sub>
 affinity of HbA<sub>1c</sub>
 seems all the more likely, with the consideration that other stimuli, able to shift the O<sub>2</sub>
Hb dissociation curve to the right during intense exercise (Bohr effect) (<xref rid="R26" ref-type="bibr">26</xref>
), were either comparable (blood pH, erythrocyte 2,3-DPG) or higher (PaCO<sub>2</sub>
) in the poorly controlled patients compared with those in healthy controls.</p>
<p>Thirdly, we cannot exclude the possibility that the exercise-induced switch of muscle blood flow from the “nonnutritive” route (i.e., the flow “reserve” irrigating muscle connective tissues and their associated adipocytes) to the “nutritive” route (i.e., capillaries in intimate contact with the skeletal muscle fibrils) (<xref rid="R12" ref-type="bibr">12</xref>
) was impaired in our poorly controlled patients with long-standing diabetes, hence reducing overall O<sub>2</sub>
 extraction proportion. This phenomenon has never been investigated <italic>in vivo</italic>
 during exercise in humans with type 1 diabetes but can be suggested through previous work on animal models of diabetes (<xref rid="R31" ref-type="bibr">31</xref>
).</p>
<p>Notwithstanding, the lower HHb increase in the vastus lateralis muscle found in the patients with inadequate glycemic control may contribute to their impaired aerobic fitness because we detected significant positive correlation between V˙O<sub>2max</sub>
 and ΔHHb at maximal exercise in all the patients with type 1 diabetes (<italic>r</italic>
 = 0.54, <italic>P</italic>
 < 0.01).</p>
<p>Further studies are needed to determine whether the blunted HHb increase in muscles observed in patients with poor glycemic control may also be related to impaired muscle mitochondrial function.</p>
</sec>
</sec>
</sec>
<sec sec-type="conclusion"><title>CONCLUSIONS</title>
<p>In summary, the ΔHHb increase in the vastus lateralis during maximal exercise is blunted in patients with type 1 diabetes and with high levels of HbA<sub>1c</sub>
. This result, obtained <italic>in vivo</italic>
 during a physiological condition, supports the hypotheses of an increase in O<sub>2</sub>
 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow routes, as previously put forward by <italic>in vitro</italic>
 and <italic>animal</italic>
 studies, respectively. This finding is of particular clinical relevance, considering the negative correlation between ΔHHb increase and V˙O<sub>2max</sub>
 found in patients with type 1 diabetes in the current study.</p>
<p>Ultimately, from a practical perspective, maximal exercise coupled with NIRS measurement represents a promising noninvasive method of physiologically assessing disorders of muscle perfusion in patients without otherwise clinically detectable microangiopathy. Determining whether these disorders of muscle blood expansion can be reversed with HbA<sub>1c</sub>
 improvement will be a challenge for future prospective clinical trials.</p>
</sec>
</body>
<back><ack><p>The authors would like to thank Dr. P. Rasoamanana, F. Dehaut, and A. Watry for laboratory assistance, Pr. A. Duhamel and Dr. H. Béhal for statistical assistance, as well as Dr. K. Volterman and Pr. J. Kerr-Conte for revising the English.</p>
<p>This study was supported by grants from ALFEDIAM-Roche Diagnostics (2009) and from an interregional hospital program of clinical research (PHRC) (2010).</p>
<p>S. T. performed the experiments, analyzed the data, and wrote the manuscript. E. L. performed the experiments, contributed to the discussion, and reviewed the manuscript. P. F. contributed to the conception of the experiments, recruited the patients, and reviewed the manuscript. R. M. contributed to the conception of the experiments and reviewed the manuscript. G. M. performed the experiments. J. A. performed the experiments and reviewed the manuscript. A. D. recruited the patients and reviewed the manuscript. A. V. recruited the patients. K. O. performed the experiments. G. B. researched data and reviewed the manuscript. E. H. is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. She conceived and designed the experiments, performed the experiments, analyzed data, and wrote the manuscript.</p>
<p>This study is registered as a clinical trial, NCT02051504, at ClinicalTrial.gov.</p>
<p>The authors have nothing to disclose.</p>
<p>The results of the present study do not constitute endorsement by the American College of Sports Medicine.</p>
</ack>
<ref-list><title>REFERENCES</title>
<ref id="R1"><label>1.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Arturson</surname>
<given-names>G</given-names>
</name>
<name><surname>Garby</surname>
<given-names>L</given-names>
</name>
<name><surname>Robert</surname>
<given-names>M</given-names>
</name>
<name><surname>Zaar</surname>
<given-names>B</given-names>
</name>
</person-group>
<article-title>Oxygen affinity of whole blood in vivo and under standard conditions in subjects with diabetes mellitus</article-title>.
<source><italic>Scand J Clin Lab Invest</italic>
</source>. 
<year>1974</year>;
<volume>34</volume>
<issue>(1)</issue>:
<fpage>19</fpage>–
<lpage>22</lpage>
.<pub-id pub-id-type="pmid">4414967</pub-id>
</mixed-citation>
</ref>
<ref id="R2"><label>2.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Aspenes</surname>
<given-names>ST</given-names>
</name>
<name><surname>Nilsen</surname>
<given-names>TIL</given-names>
</name>
<name><surname>Skaug</surname>
<given-names>EA</given-names>
</name>
</person-group>
<article-title>Peak oxygen uptake and cardiovascular risk factors in 4631 healthy women and men</article-title>.
<source><italic>Med Sci Sports Exerc</italic>
</source>. 
<year>2011</year>;
<volume>43</volume>
<issue>(8)</issue>:
<fpage>1465</fpage>–
<lpage>73</lpage>
.<pub-id pub-id-type="pmid">21228724</pub-id>
</mixed-citation>
</ref>
<ref id="R3"><label>3.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Astorino</surname>
<given-names>TA</given-names>
</name>
<name><surname>White</surname>
<given-names>AC</given-names>
</name>
<name><surname>Dalleck</surname>
<given-names>LC</given-names>
</name>
</person-group>
<article-title>Supramaximal testing to confirm attainment of O2max in sedentary men and women</article-title>.
<source><italic>Int J Sports Med</italic>
</source>. 
<year>2009</year>;
<volume>30</volume>
<issue>(4)</issue>:
<fpage>279</fpage>–
<lpage>84</lpage>
.<pub-id pub-id-type="pmid">19199208</pub-id>
</mixed-citation>
</ref>
<ref id="R4"><label>4.</label>
<mixed-citation publication-type="book"><person-group><name><surname>Astrand</surname>
<given-names>PO</given-names>
</name>
<name><surname>Rodahl</surname>
<given-names>K</given-names>
</name>
<name><surname>Dahl</surname>
<given-names>HA</given-names>
</name>
<name><surname>Stromme</surname>
<given-names>SB</given-names>
</name>
</person-group>
<source><italic>Textbook of Work Physiology—4th: Physiological Bases of Exercise</italic>
</source>
. <edition>4th ed</edition>
<comment> Champaign (IL):</comment>
<publisher-name>Human Kinetics</publisher-name>; 
<year>2003</year> p. 
<fpage>656</fpage>
.</mixed-citation>
</ref>
<ref id="R5"><label>5.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Baldi</surname>
<given-names>JC</given-names>
</name>
<name><surname>Cassuto</surname>
<given-names>NA</given-names>
</name>
<name><surname>Foxx-Lupo</surname>
<given-names>WT</given-names>
</name>
<name><surname>Wheatley</surname>
<given-names>CM</given-names>
</name>
<name><surname>Snyder</surname>
<given-names>EM</given-names>
</name>
</person-group>
<article-title>Glycemic status affects cardiopulmonary exercise response in athletes with type I diabetes</article-title>.
<source><italic>Med Sci Sports Exerc</italic>
</source>. 
<year>2010</year>;
<volume>42</volume>
<issue>(8)</issue>:
<fpage>1454</fpage>–
<lpage>9</lpage>
.<pub-id pub-id-type="pmid">20139786</pub-id>
</mixed-citation>
</ref>
<ref id="R6"><label>6.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Bassett</surname>
<given-names>DR</given-names>
<suffix>Jr</suffix>
</name>
<name><surname>Howley</surname>
<given-names>ET</given-names>
</name>
</person-group>
<article-title>Limiting factors for maximum oxygen uptake and determinants of endurance performance</article-title>.
<source><italic>Med Sci Sports Exerc</italic>
</source>. 
<year>2000</year>;
<volume>32</volume>
<issue>(1)</issue>:
<fpage>70</fpage>–
<lpage>84</lpage>
.<pub-id pub-id-type="pmid">10647532</pub-id>
</mixed-citation>
</ref>
<ref id="R7"><label>7.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Bhambhani</surname>
<given-names>YN</given-names>
</name>
</person-group>
<article-title>Muscle oxygenation trends during dynamic exercise measured by near infrared spectroscopy</article-title>.
<source><italic>Can J Appl Physiol</italic>
</source>. 
<year>2004</year>;
<volume>29</volume>
<issue>(4)</issue>:
<fpage>504</fpage>–
<lpage>23</lpage>
.<pub-id pub-id-type="pmid">15328597</pub-id>
</mixed-citation>
</ref>
<ref id="R8"><label>8.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Bodnar</surname>
<given-names>PN</given-names>
</name>
<name><surname>Pristupiuk</surname>
<given-names>AM</given-names>
</name>
</person-group>
<article-title>Assessment of the 2,3-diphosphoglycerate content of erythrocytes in diabetes mellitus [in Russian]</article-title>.
<source><italic>Probl Endokrinol (Mosk)</italic>
</source>. 
<year>1982</year>;
<volume>28</volume>
<issue>(5)</issue>:
<fpage>15</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">7145879</pub-id>
</mixed-citation>
</ref>
<ref id="R9"><label>9.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Brazeau</surname>
<given-names>AS</given-names>
</name>
<name><surname>Rabasa-Lhoret</surname>
<given-names>R</given-names>
</name>
<name><surname>Strychar</surname>
<given-names>I</given-names>
</name>
<name><surname>Mircescu</surname>
<given-names>H</given-names>
</name>
</person-group>
<article-title>Barriers to physical activity among patients with type 1 diabetes</article-title>.
<source><italic>Diabetes Care</italic>
</source>. 
<year>2008</year>;
<volume>31</volume>
<issue>(11)</issue>:
<fpage>2108</fpage>–
<lpage>9</lpage>
.<pub-id pub-id-type="pmid">18689694</pub-id>
</mixed-citation>
</ref>
<ref id="R10"><label>10.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Bunn</surname>
<given-names>HF</given-names>
</name>
<name><surname>Briehl</surname>
<given-names>RW</given-names>
</name>
</person-group>
<article-title>The interaction of 2,3-diphosphoglycerate with various human hemoglobins</article-title>.
<source><italic>J Clin Invest</italic>
</source>. 
<year>1970</year>;
<volume>49</volume>
<issue>(6)</issue>:
<fpage>1088</fpage>–
<lpage>95</lpage>
.<pub-id pub-id-type="pmid">5422014</pub-id>
</mixed-citation>
</ref>
<ref id="R11"><label>11.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Chance</surname>
<given-names>WW</given-names>
</name>
<name><surname>Rhee</surname>
<given-names>C</given-names>
</name>
<name><surname>Yilmaz</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Diminished alveolar microvascular reserves in type 2 diabetes reflect systemic microangiopathy</article-title>.
<source><italic>Diabetes Care</italic>
</source>. 
<year>2008</year>;
<volume>31</volume>
<issue>(8)</issue>:
<fpage>1596</fpage>–
<lpage>601</lpage>
.<pub-id pub-id-type="pmid">18492945</pub-id>
</mixed-citation>
</ref>
<ref id="R12"><label>12.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Clark</surname>
<given-names>MG</given-names>
</name>
<name><surname>Rattigan</surname>
<given-names>S</given-names>
</name>
<name><surname>Clerk</surname>
<given-names>LH</given-names>
</name>
</person-group>
<article-title>Nutritive and non-nutritive blood flow: rest and exercise</article-title>.
<source><italic>Acta Physiol Scand</italic>
</source>. 
<year>2000</year>;
<volume>168</volume>
<issue>(4)</issue>:
<fpage>519</fpage>–
<lpage>30</lpage>
.<pub-id pub-id-type="pmid">10759589</pub-id>
</mixed-citation>
</ref>
<ref id="R13"><label>13.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>DeLorey</surname>
<given-names>DS</given-names>
</name>
<name><surname>Kowalchuk</surname>
<given-names>JM</given-names>
</name>
<name><surname>Paterson</surname>
<given-names>DH</given-names>
</name>
</person-group>
<article-title>Adaptation of pulmonary O2 uptake kinetics and muscle deoxygenation at the onset of heavy-intensity exercise in young and older adults</article-title>.
<source><italic>J Appl Physiol (1985)</italic>
</source>. 
<year>2005</year>;
<volume>98</volume>
<issue>(5)</issue>:
<fpage>1697</fpage>–
<lpage>704</lpage>
.<pub-id pub-id-type="pmid">15640394</pub-id>
</mixed-citation>
</ref>
<ref id="R14"><label>14.</label>
<mixed-citation publication-type="journal"><article-title>Diabetes mellitus. Report of a WHO Study Group</article-title>.
<source><italic>World Health Organ Tech Rep Ser</italic>
</source>. 
<year>1985</year>;
<volume>727</volume>: 
<fpage>1</fpage>–
<lpage>113</lpage>
.<pub-id pub-id-type="pmid">3934850</pub-id>
</mixed-citation>
</ref>
<ref id="R15"><label>15.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Ditzel</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Affinity hypoxia as a pathogenetic factor of microangiopathy with particular reference to diabetic retinopathy</article-title>.
<source><italic>Acta Endocrinol Suppl (Copenh)</italic>
</source>. 
<year>1980</year>;
<volume>238</volume>:
<fpage>39</fpage>–
<lpage>55</lpage>
.<pub-id pub-id-type="pmid">6933814</pub-id>
</mixed-citation>
</ref>
<ref id="R16"><label>16.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Ditzel</surname>
<given-names>J</given-names>
</name>
<name><surname>Kjaergaard</surname>
<given-names>JJ</given-names>
</name>
</person-group>
<article-title>Haemoglobin AIc concentrations after initial insulin treatment for newly discovered diabetes</article-title>.
<source><italic>Br Med J</italic>
</source>. 
<year>1978</year>;
<volume>1</volume>
<issue>(6115)</issue>:
<fpage>741</fpage>–
<lpage>2</lpage>
.<pub-id pub-id-type="pmid">630325</pub-id>
</mixed-citation>
</ref>
<ref id="R17"><label>17.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Esposito</surname>
<given-names>F</given-names>
</name>
<name><surname>Mathieu-Costello</surname>
<given-names>O</given-names>
</name>
<name><surname>Shabetai</surname>
<given-names>R</given-names>
</name>
<name><surname>Wagner</surname>
<given-names>PD</given-names>
</name>
<name><surname>Richardson</surname>
<given-names>RS</given-names>
</name>
</person-group>
<article-title>Limited maximal exercise capacity in patients with chronic heart failure: partitioning the contributors</article-title>.
<source><italic>J Am Coll Cardiol</italic>
</source>. 
<year>2010</year>;
<volume>55</volume>
<issue>(18)</issue>:
<fpage>1945</fpage>–
<lpage>54</lpage>
.<pub-id pub-id-type="pmid">20430267</pub-id>
</mixed-citation>
</ref>
<ref id="R18"><label>18.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Ferrari</surname>
<given-names>M</given-names>
</name>
<name><surname>Muthalib</surname>
<given-names>M</given-names>
</name>
<name><surname>Quaresima</surname>
<given-names>V</given-names>
</name>
</person-group>
<article-title>The use of near-infrared spectroscopy in understanding skeletal muscle physiology: recent developments</article-title>.
<source><italic>Philos Transact A Math Phys Eng Sci</italic>
</source>. 
<year>2011</year>;
<volume>369</volume>
<issue>(1955)</issue>:
<fpage>4577</fpage>–
<lpage>90</lpage>
.</mixed-citation>
</ref>
<ref id="R19"><label>19.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Grassi</surname>
<given-names>B</given-names>
</name>
<name><surname>Pogliaghi</surname>
<given-names>S</given-names>
</name>
<name><surname>Rampichini</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Muscle oxygenation and pulmonary gas exchange kinetics during cycling exercise on-transitions in humans</article-title>.
<source><italic>J Appl Physiol (1985)</italic>
</source>. 
<year>2003</year>;
<volume>95</volume>
<issue>(1)</issue>:
<fpage>149</fpage>–
<lpage>58</lpage>
.<pub-id pub-id-type="pmid">12611769</pub-id>
</mixed-citation>
</ref>
<ref id="R20"><label>20.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Jones</surname>
<given-names>MD</given-names>
</name>
<name><surname>Booth</surname>
<given-names>J</given-names>
</name>
<name><surname>Taylor</surname>
<given-names>JL</given-names>
</name>
<name><surname>Barry</surname>
<given-names>BK</given-names>
</name>
</person-group>
<article-title>Aerobic training increases pain tolerance in healthy individuals</article-title>.
<source><italic>Med Sci Sports Exerc</italic>
</source>. 
<year>2014</year>;
<volume>46</volume>
<issue>(8)</issue>:
<fpage>1640</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">24504426</pub-id>
</mixed-citation>
</ref>
<ref id="R21"><label>21.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Komatsu</surname>
<given-names>WR</given-names>
</name>
<name><surname>Barros Neto</surname>
<given-names>TL</given-names>
</name>
<name><surname>Chacra</surname>
<given-names>AR</given-names>
</name>
<name><surname>Dib</surname>
<given-names>SA</given-names>
</name>
</person-group>
<article-title>Aerobic exercise capacity and pulmonary function in athletes with and without type 1 diabetes</article-title>.
<source><italic>Diabetes Care</italic>
</source>. 
<year>2010</year>;
<volume>33</volume>
<issue>(12)</issue>:
<fpage>2555</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">20807874</pub-id>
</mixed-citation>
</ref>
<ref id="R22"><label>22.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Lakoski</surname>
<given-names>SG</given-names>
</name>
<name><surname>Barlow</surname>
<given-names>CE</given-names>
</name>
<name><surname>Farrell</surname>
<given-names>SW</given-names>
</name>
<name><surname>Berry</surname>
<given-names>JD</given-names>
</name>
<name><surname>Morrow</surname>
<given-names>JR</given-names>
<suffix>Jr</suffix>
</name>
<name><surname>Haskell</surname>
<given-names>WL</given-names>
</name>
</person-group>
<article-title>Impact of body mass index, physical activity, and other clinical factors on cardiorespiratory fitness (from the Cooper Center longitudinal study)</article-title>.
<source><italic>Am J Cardiol</italic>
</source>. 
<year>2011</year>;
<volume>108</volume>
<issue>(1)</issue>:
<fpage>34</fpage>–
<lpage>9</lpage>
.<pub-id pub-id-type="pmid">21529738</pub-id>
</mixed-citation>
</ref>
<ref id="R23"><label>23.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Laplaud</surname>
<given-names>D</given-names>
</name>
<name><surname>Hug</surname>
<given-names>F</given-names>
</name>
<name><surname>Grélot</surname>
<given-names>L</given-names>
</name>
</person-group>
<article-title>Reproducibility of eight lower limb muscles activity level in the course of an incremental pedaling exercise</article-title>.
<source><italic>J Electromyogr Kinesiol</italic>
</source>. 
<year>2006</year>;
<volume>16</volume>
<issue>(2)</issue>:
<fpage>158</fpage>–
<lpage>66</lpage>
.<pub-id pub-id-type="pmid">16126412</pub-id>
</mixed-citation>
</ref>
<ref id="R24"><label>24.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Lukács</surname>
<given-names>A</given-names>
</name>
<name><surname>Mayer</surname>
<given-names>K</given-names>
</name>
<name><surname>Juhász</surname>
<given-names>E</given-names>
</name>
<name><surname>Varga</surname>
<given-names>B</given-names>
</name>
<name><surname>Fodor</surname>
<given-names>B</given-names>
</name>
<name><surname>Barkai</surname>
<given-names>L</given-names>
</name>
</person-group>
<article-title>Reduced physical fitness in children and adolescents with type 1 diabetes</article-title>.
<source><italic>Pediatr Diabetes</italic>
</source>. 
<year>2012</year>;
<volume>13</volume>
<issue>(5)</issue>:
<fpage>432</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">22353226</pub-id>
</mixed-citation>
</ref>
<ref id="R25"><label>25.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Marschner</surname>
<given-names>JP</given-names>
</name>
<name><surname>Seidlitz</surname>
<given-names>T</given-names>
</name>
<name><surname>Rietbrock</surname>
<given-names>N</given-names>
</name>
</person-group>
<article-title>Effect of 2,3-diphosphoglycerate on O2-dissociation kinetics of hemoglobin and glycosylated hemoglobin using the stopped flow technique and an improved in vitro method for hemoglobin glycosylation</article-title>.
<source><italic>Int J Clin Pharmacol Ther</italic>
</source>. 
<year>1994</year>;
<volume>32</volume>
<issue>(3)</issue>:
<fpage>116</fpage>–
<lpage>21</lpage>
.<pub-id pub-id-type="pmid">8205371</pub-id>
</mixed-citation>
</ref>
<ref id="R26"><label>26.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>McDonald</surname>
<given-names>MJ</given-names>
</name>
<name><surname>Bleichman</surname>
<given-names>M</given-names>
</name>
<name><surname>Bunn</surname>
<given-names>HF</given-names>
</name>
<name><surname>Noble</surname>
<given-names>RW</given-names>
</name>
</person-group>
<article-title>Functional properties of the glycosylated minor components of human adult hemoglobin</article-title>.
<source><italic>J Biol Chem</italic>
</source>. 
<year>1979</year>;
<volume>254</volume>
<issue>(3)</issue>:
<fpage>702</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">33173</pub-id>
</mixed-citation>
</ref>
<ref id="R27"><label>27.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Mollard</surname>
<given-names>P</given-names>
</name>
<name><surname>Bourdillon</surname>
<given-names>N</given-names>
</name>
<name><surname>Letournel</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>Validity of arterialized earlobe blood gases at rest and exercise in normoxia and hypoxia</article-title>.
<source><italic>Respir Physiol Neurobiol</italic>
</source>. 
<year>2010</year>;
<volume>172</volume>
<issue>(3)</issue>:
<fpage>179</fpage>–
<lpage>83</lpage>
.<pub-id pub-id-type="pmid">20493971</pub-id>
</mixed-citation>
</ref>
<ref id="R28"><label>28.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Nadeau</surname>
<given-names>KJ</given-names>
</name>
<name><surname>Regensteiner</surname>
<given-names>JG</given-names>
</name>
<name><surname>Bauer</surname>
<given-names>TA</given-names>
</name>
</person-group>
<article-title>Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function</article-title>.
<source><italic>J Clin Endocrinol Metab</italic>
</source>. 
<year>2010</year>;
<volume>95</volume>
<issue>(2)</issue>:
<fpage>513</fpage>–
<lpage>21</lpage>
.<pub-id pub-id-type="pmid">19915016</pub-id>
</mixed-citation>
</ref>
<ref id="R29"><label>29.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Nielsen</surname>
<given-names>HB</given-names>
</name>
<name><surname>Madsen</surname>
<given-names>P</given-names>
</name>
<name><surname>Svendsen</surname>
<given-names>LB</given-names>
</name>
<name><surname>Roach</surname>
<given-names>RC</given-names>
</name>
<name><surname>Secher</surname>
<given-names>NH</given-names>
</name>
</person-group>
<article-title>The influence of PaO2, pH and SaO2 on maximal oxygen uptake</article-title>.
<source><italic>Acta Physiol Scand</italic>
</source>. 
<year>1998</year>;
<volume>164</volume>
<issue>(1)</issue>:
<fpage>89</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">9777029</pub-id>
</mixed-citation>
</ref>
<ref id="R30"><label>30.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Niranjan</surname>
<given-names>V</given-names>
</name>
<name><surname>McBrayer</surname>
<given-names>DG</given-names>
</name>
<name><surname>Ramirez</surname>
<given-names>LC</given-names>
</name>
<name><surname>Raskin</surname>
<given-names>P</given-names>
</name>
<name><surname>Hsia</surname>
<given-names>CC</given-names>
</name>
</person-group>
<article-title>Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus</article-title>.
<source><italic>Am J Med</italic>
</source>. 
<year>1997</year>;
<volume>103</volume>
<issue>(6)</issue>:
<fpage>504</fpage>–
<lpage>13</lpage>
.<pub-id pub-id-type="pmid">9428834</pub-id>
</mixed-citation>
</ref>
<ref id="R31"><label>31.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Padilla</surname>
<given-names>DJ</given-names>
</name>
<name><surname>McDonough</surname>
<given-names>P</given-names>
</name>
<name><surname>Behnke</surname>
<given-names>BJ</given-names>
</name>
</person-group>
<article-title>Effects of Type II diabetes on capillary hemodynamics in skeletal muscle</article-title>.
<source><italic>Am J Physiol Heart Circ Physiol</italic>
</source>. 
<year>2006</year>;
<volume>291</volume>
<issue>(5)</issue>:
<fpage>H2439</fpage>–
<lpage>44</lpage>
.<pub-id pub-id-type="pmid">16844923</pub-id>
</mixed-citation>
</ref>
<ref id="R32"><label>32.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Peltonen</surname>
<given-names>JE</given-names>
</name>
<name><surname>Koponen</surname>
<given-names>AS</given-names>
</name>
<name><surname>Pullinen</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Alveolar gas exchange and tissue deoxygenation during exercise in type 1 diabetes patients and healthy controls</article-title>.
<source><italic>Respir Physiol Neurobiol</italic>
</source>. 
<year>2012</year>;
<volume>181</volume>
<issue>(3)</issue>:
<fpage>267</fpage>–
<lpage>76</lpage>
.<pub-id pub-id-type="pmid">22538274</pub-id>
</mixed-citation>
</ref>
<ref id="R33"><label>33.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Pichler</surname>
<given-names>G</given-names>
</name>
<name><surname>Urlesberger</surname>
<given-names>B</given-names>
</name>
<name><surname>Jirak</surname>
<given-names>P</given-names>
</name>
</person-group>
<article-title>Reduced forearm blood flow in children and adolescents with type 1 diabetes (measured by near-infrared spectroscopy)</article-title>.
<source><italic>Diabetes Care</italic>
</source>. 
<year>2004</year>;
<volume>27</volume>
<issue>(8)</issue>:
<fpage>1942</fpage>–
<lpage>6</lpage>
.<pub-id pub-id-type="pmid">15277421</pub-id>
</mixed-citation>
</ref>
<ref id="R34"><label>34.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Plasqui</surname>
<given-names>G</given-names>
</name>
<name><surname>Westerterp</surname>
<given-names>KR</given-names>
</name>
</person-group>
<article-title>Accelerometry and heart rate as a measure of physical fitness: proof of concept</article-title>.
<source><italic>Med Sci Sports Exerc</italic>
</source>. 
<year>2005</year>;
<volume>37</volume>
<issue>(5)</issue>:
<fpage>872</fpage>–
<lpage>6</lpage>
.<pub-id pub-id-type="pmid">15870644</pub-id>
</mixed-citation>
</ref>
<ref id="R35"><label>35.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Poortmans</surname>
<given-names>JR</given-names>
</name>
<name><surname>Saerens</surname>
<given-names>P</given-names>
</name>
<name><surname>Edelman</surname>
<given-names>R</given-names>
</name>
<name><surname>Vertongen</surname>
<given-names>F</given-names>
</name>
<name><surname>Dorchy</surname>
<given-names>H</given-names>
</name>
</person-group>
<article-title>Influence of the degree of metabolic control on physical fitness in type I diabetic adolescents</article-title>.
<source><italic>Int J Sports Med</italic>
</source>. 
<year>1986</year>;
<volume>7</volume>
<issue>(4)</issue>:
<fpage>232</fpage>–
<lpage>5</lpage>
.<pub-id pub-id-type="pmid">3759305</pub-id>
</mixed-citation>
</ref>
<ref id="R36"><label>36.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Roberts</surname>
<given-names>AP</given-names>
</name>
<name><surname>Story</surname>
<given-names>CJ</given-names>
</name>
<name><surname>Ryall</surname>
<given-names>RG</given-names>
</name>
</person-group>
<article-title>Erythrocyte 2,3-bisphosphoglycerate concentrations and haemoglobin glycosylation in normoxic type 1 (insulin-dependent) diabetes mellitus</article-title>.
<source><italic>Diabetologia</italic>
</source>. 
<year>1984</year>;
<volume>26</volume>
<issue>(5)</issue>:
<fpage>389</fpage>–
<lpage>91</lpage>
.<pub-id pub-id-type="pmid">6734983</pub-id>
</mixed-citation>
</ref>
<ref id="R37"><label>37.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Roca</surname>
<given-names>J</given-names>
</name>
<name><surname>Agusti</surname>
<given-names>AG</given-names>
</name>
<name><surname>Alonso</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Effects of training on muscle O2 transport at VO2max</article-title>.
<source><italic>J Appl Physiol (1985)</italic>
</source>. 
<year>1992</year>;
<volume>73</volume>
<issue>(3)</issue>:
<fpage>1067</fpage>–
<lpage>76</lpage>
.<pub-id pub-id-type="pmid">1400019</pub-id>
</mixed-citation>
</ref>
<ref id="R38"><label>38.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Wanke</surname>
<given-names>T</given-names>
</name>
<name><surname>Formanek</surname>
<given-names>D</given-names>
</name>
<name><surname>Auinger</surname>
<given-names>M</given-names>
</name>
<name><surname>Zwick</surname>
<given-names>H</given-names>
</name>
<name><surname>Irsigler</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Pulmonary gas exchange and oxygen uptake during exercise in patients with type 1 diabetes mellitus</article-title>.
<source><italic>Diabet Med</italic>
</source>. 
<year>1992</year>;
<volume>9</volume>
<issue>(3)</issue>:
<fpage>252</fpage>–
<lpage>7</lpage>
.<pub-id pub-id-type="pmid">1576807</pub-id>
</mixed-citation>
</ref>
<ref id="R39"><label>39.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Wheatley</surname>
<given-names>CM</given-names>
</name>
<name><surname>Baldi</surname>
<given-names>JC</given-names>
</name>
<name><surname>Cassuto</surname>
<given-names>NA</given-names>
</name>
<name><surname>Foxx-Lupo</surname>
<given-names>WT</given-names>
</name>
<name><surname>Snyder</surname>
<given-names>EM</given-names>
</name>
</person-group>
<article-title>Glycemic control influences lung membrane diffusion and oxygen saturation in exercise-trained subjects with type 1 diabetes: alveolar-capillary membrane conductance in type 1 diabetes</article-title>.
<source><italic>Eur J Appl Physiol</italic>
</source>. 
<year>2011</year>;
<volume>111</volume>
<issue>(3)</issue>:
<fpage>567</fpage>–
<lpage>78</lpage>
.<pub-id pub-id-type="pmid">20936482</pub-id>
</mixed-citation>
</ref>
<ref id="R40"><label>40.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Whipp</surname>
<given-names>BJ</given-names>
</name>
<name><surname>Higgenbotham</surname>
<given-names>MB</given-names>
</name>
<name><surname>Cobb</surname>
<given-names>FC</given-names>
</name>
</person-group>
<article-title>Estimating exercise stroke volume from asymptotic oxygen pulse in humans</article-title>.
<source><italic>J Appl Physiol (1985)</italic>
</source>. 
<year>1996</year>;
<volume>81</volume>
<issue>(6)</issue>:
<fpage>2674</fpage>–
<lpage>9</lpage>
.<pub-id pub-id-type="pmid">9018521</pub-id>
</mixed-citation>
</ref>
<ref id="R41"><label>41.</label>
<mixed-citation publication-type="journal"><person-group><name><surname>Womack</surname>
<given-names>L</given-names>
</name>
<name><surname>Peters</surname>
<given-names>D</given-names>
</name>
<name><surname>Barrett</surname>
<given-names>EJ</given-names>
</name>
<name><surname>Kaul</surname>
<given-names>S</given-names>
</name>
<name><surname>Price</surname>
<given-names>W</given-names>
</name>
<name><surname>Lindner</surname>
<given-names>JR</given-names>
</name>
</person-group>
<article-title>Abnormal skeletal muscle capillary recruitment during exercise in patients with type 2 diabetes mellitus and microvascular complications</article-title>.
<source><italic>J Am Coll Cardiol</italic>
</source>. 
<year>2009</year>;
<volume>53</volume>
<issue>(23)</issue>:
<fpage>2175</fpage>–
<lpage>83</lpage>
.<pub-id pub-id-type="pmid">19497445</pub-id>
</mixed-citation>
</ref>
</ref-list>
</back>
</pmc>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Belgique/explor/OpenAccessBelV2/Data/Pmc/Corpus

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000397 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000397 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Belgique
   |area=    OpenAccessBelV2
   |flux=    Pmc
   |étape=   Corpus
   |type=    RBID
   |clé=     PMC:4323553
   |texte=   Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i   -Sk "pubmed:24983346" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd   \
       | NlmPubMed2Wicri -a OpenAccessBelV2

This area was generated with Dilib version V0.6.25.
Data generation: Thu Dec 1 00:43:49 2016. Site generation: Wed Mar 6 14:51:30 2024

	Serveur d'exploration autour du libre accès en Belgique
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration autour du libre accès en Belgique

Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

Source :

Abstract

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki