title: Association between cardiorespiratory fitness and the determinants of glycemic control across the entire glucose tolerance continuum.
abstract: OBJECTIVE
  Cardiorespiratory fitness (VO2max) is associated with glycemic control, yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum.
  
  
  METHODS
  A cohort of subjects (N = 313) with heterogeneous age, sex, BMI, and glycemic control underwent measurements of body composition, HbA1c, fasting glucose, oral glucose tolerance (OGTT), and VO2max. OGTT-derived insulin sensitivity (SiOGTT), glucose-stimulated insulin secretion (GSISOGTT), and the disposition index (DIOGTT) (the product of SiOGTT and GSISOGTT) were measured, and associations between VO2max and these determinants of glycemic control were examined.
  
  
  RESULTS
  A low VO2max was associated with high HbA1c (r = -0.33), high fasting glucose (r = -0.34), high 2-h OGTT glucose (r = -0.33), low SiOGTT (r = 0.73), and high early-phase (r = -0.34) and late-phase (r = -0.36) GSISOGTT. Furthermore, a low VO2max was associated with low early- and late-phase DIOGTT (both r = 0.41). Interestingly, relationships between VO2max and either glycemic control or late-phase GSISOGTT deteriorated across the glucose tolerance continuum.
  
  
  CONCLUSIONS
  The association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes.
authors.affiliation: Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark thomas.solomon@sund.ku.dk.
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Solomon
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Karstoft
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Sine H
authors.initials: SH
authors.lastname: Knudsen
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Haus
authors.affiliation: Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Laye
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH Metabolic Translational Research Center, Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000517:prevention & control; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin