title: Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity.
abstract: OBJECTIVE
  Non-invasive measures of aortic stiffness reflect vascular senescence and predict outcome in diabetes. Glucose-mediated elastic artery sclerosis may play an integral role in the development of macrovascular complications. We used carotid-femoral pulse wave velocity ((cf)PWV) to quantify independent associations of fasting glucose, post-challenge glucose and derived insulin resistance (HOMA-IR) with aortic stiffness.
  
  
  METHODS
  (cf)PWV was measured using a 4 MHz continuous wave Doppler ultrasound probe within groups with newly identified age- and sex-matched normal glucose metabolism (NGM), impaired glucose regulation (IGR) and diabetes mellitus populations (n = 570, mean age 59.1, 56% male).
  
  
  RESULTS
  After multivariate adjustment, IGR and diabetes were associated with significant aortic stiffening compared with NGM (adjusted (cf)PWV+/-SE: NGM, 9.15 +/- 0.12 m/s; IGR 9.76 +/- 0.11 m/s, p < 0.001; diabetes, 9.89 +/- 0.12 m/s, p < 0.001). IGR stratification indicated that impaired fasting glucose (IFG; 9.71 +/- 0.12 m/s) and post-challenge (impaired glucose tolerance; 9.82 +/- 0.24 m/s) categories had similar (cf)PWV (p = 0.83). Modelled predictors of (cf)PWV were used to assess independent metabolic associations with arterial stiffness. Fasting glucose concentration (beta = 0.10; 95% CI 0.05, 0.18; p = 0.003), 2 h post-challenge glucose (beta = 0.14; 95% CI 0.02, 0.23; p < 0.001) and HOMA-IR (beta = 0.20, 95% CI 0.05, 0.53; p < 0.001) were independently related to (cf)PWV after adjustment for age, sex, mean arterial pressure, heart rate, body mass index, renal function and antihypertensive medication.
  
  
  CONCLUSIONS
  IGR characterised by fasting or post-challenge hyperglycaemia is associated with significant vascular stiffening. Post-challenge glucose and HOMA-IR are the most powerful metabolic predictors of arterial stiffness, implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of arteriosclerosis.
authors.affiliation: Diabetes and Vascular Research Group, Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 5WW, UK. david.webb@uhl-tr.nhs.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Webb
authors.forename: K
authors.initials: K
authors.lastname: Khunti
authors.forename: R
authors.initials: R
authors.lastname: Silverman
authors.forename: L J
authors.initials: LJ
authors.lastname: Gray
authors.forename: B
authors.initials: B
authors.lastname: Srinivasan
authors.forename: P S
authors.initials: PS
authors.lastname: Lacy
authors.forename: B
authors.initials: B
authors.lastname: Williams
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001011:Aorta / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow / Q000502:physiology; D012044:Regression Analysis; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D001786:Blood Glucose