title: A computational model of the effect of capillary density variability on oxygen transport, glucose uptake, and insulin sensitivity in prediabetes.
abstract: The purpose of this study was to model how CD variability affects tissue oxygenation under resting and exercise conditions. Additionally, we examine how CD impacts glucose and insulin transport in skeletal muscle.
  
  
  
  We applied an established 3D finite difference model of oxygen transport to predict tissue oxygenation using FCD, hemodynamics, and SO2measurements from a previous study. A 2D finite element model of glucose transport was applied to predict glucose and insulin uptake in PP and fasting conditions using the same range of CD.
  
  
  
  Control simulations used CD ranging from 562.5 to 781.3 capillaries/mm2, whereas prediabetic densities ranged from 375.0 to 593.8 capillaries/mm2. Mean tissue PO2was 30.6±4.6 to 40.5±3.6 mm Hg for rest and 19.6±6.7 to 33.27±4.7 mm Hg for control and prediabetic simulations, respectively. Mean PP glucose concentrations were 5.85±1.13 mmol/L in the control group and 5.11±1.28 in the prediabetic simulations. Glucose uptake rates were 35% lower in the lowest capillary CD case compared to the high CD simulation.
  
  
  
  Our simulations predict that CD decreases can have a substantial effect on oxygen delivery and glucose disposal across the observed physiological ranges of capillarization.
authors.affiliation: Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sové
authors.affiliation: Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Cardiovascular Research Group, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Graham M
authors.identifier: 0000-0002-5733-201X
authors.initials: GM
authors.lastname: Fraser
mesh_terms: D000818:Animals; D002196:Capillaries / Q000033:anatomy & histology / Q000502:physiology*; D003198:Computer Simulation; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D005082:Physical Exertion / Q000502:physiology; D011236:Prediabetic State / Q000378:metabolism*; D012146:Rest / Q000502:physiology
chemical_list: D005947:Glucose; D010100:Oxygen
keywords: diabetes mellitus; functional capillary density; insulin resistance; mathematical modeling; oxygen transport