title: Association of Exercise Intolerance in Type 2 Diabetes With Skeletal Muscle Blood Flow Reserve.
abstract: OBJECTIVE
  This study sought to investigate the association of exercise intolerance in type 2 diabetes (T2DM) with skeletal muscle capillary blood flow (CBF) reserve.
  
  
  BACKGROUND
  Exercise intolerance in T2DM strongly predicts adverse prognosis, but associations with muscle blood flow independent of cardiac dysfunction are undefined.
  
  
  METHODS
  In 134 T2DM patients without cardiovascular disease, left ventricular function and contrast-enhanced ultrasound of the quadriceps (for CBF; i.e., product of capillary blood volume and velocity) were assessed at rest and immediately following treadmill exercise for peak oxygen uptake (Vo2peak). Left ventricular systolic and diastolic functional reserve indexes were derived from changes in systolic and early diastolic color tissue Doppler velocities. Cardiac index reserve and its constituents (stroke volume and chronotropic indexes) and left ventricular filling pressure (ratio of early diastolic mitral inflow and annular velocities) were also measured.
  
  
  RESULTS
  Vo2peak correlated with muscle CBF reserve (β = 0.16, p = 0.005) independent of cardiac index reserve and clinical covariates. This was explained by higher muscle capillary blood velocity reserve (β = 0.18, p = 0.002), rather than blood volume reserve (p > 0.10) in patients with higher Vo2peak. A concurrent association of Vo2peak with cardiac index reserve (β = 0.20, p < 0.001) appeared to reflect chronotropic index (β = 0.15, p = 0.012) rather than stroke volume index reserve (p > 0.10), although the systolic functional reserve index was also identified as an independent correlate (β = 0.16, p = 0.028). No associations of Vo2peak with diastolic functional reserve were identified (p > 0.10).
  
  
  CONCLUSIONS
  Vo2peak is associated with muscle CBF reserve in T2DM, independent of parallel associations with cardiac functional reserve. This is consistent with a multifactorial basis for exercise intolerance in T2DM.
authors.affiliation: School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Australia; Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Julian W
authors.initials: JW
authors.lastname: Sacre
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Jellis
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Haluska
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Carly
authors.initials: C
authors.lastname: Jenkins
authors.affiliation: School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia. Electronic address: Tom.Marwick@utas.edu.au.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Marwick
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Keske
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003971:Diastole / Q000502:physiology; D004452:Echocardiography; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000000981:diagnostic imaging; D013599:Systole / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
keywords: contrast agents; diabetic cardiomyopathies; echocardiography; exercise test; perfusion