title: Nondiabetic Glucometabolic Status and Progression of Aortic Stiffness: The Whitehall II Study.
abstract: Aortic stiffness is an important predictor of future morbidity and mortality. Diabetes is associated with increased aortic stiffness, but the importance of nondiabetic glucometabolic status for accelerated aortic stiffening is unclear. We tested the hypothesis that adverse glucometabolic status is associated with accelerated aortic stiffening in individuals without diabetes, independently of known risk factors for arterial stiffening.
  
  
  
  Glucometabolic status and other cardiovascular risk factors were assessed at baseline in 2008-09, and carotid femoral pulse wave velocity (cfPWV) at baseline and follow-up in 2012-13, in 4,386 participants without diabetes of the Whitehall II Study.
  
  
  
  The mean age of the cohort at cfPWV baseline was 60 years, and 74% were male. cfPWV increased from (mean ± SE) 8.30 ± 0.03 to 8.98 ± 0.04 m/s during 4 years of follow-up. At baseline, cfPWV was associated with fasting and 2-h postload glucose, HbA1c, and HOMA-insulin resistance (HOMA-IR). HbA1cand HOMA-IR were associated with progression of cfPWV after adjusting for physiological confounders and cardiovascular risk factors. A 1 SD higher HbA1cand HOMA-IR were associated with greater increases in cfPWV (0.11 m/s per 5 years [95% CI 0.04, 0.18],P= 0.003 and 0.09 m/s per 5 years [0.01, 0.17],P= 0.03, respectively). Additional adjustment for BMI weakened the association with HOMA-IR but not with HbA1c.
  
  
  
  HbA1cis independently associated with accelerated progression of aortic stiffness in individuals without diabetes. These findings suggest that long-term glucometabolic status, even in individuals without diabetes, could be an important target for preventative strategies against vascular aging.
authors.affiliation: Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, U.K. cmm41@cam.ac.uk.
authors.forename: Carmel M
authors.identifier: 0000-0003-3636-0705
authors.initials: CM
authors.lastname: McEniery
authors.affiliation: Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, U.K.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.affiliation: Steno Diabetes Center A/S, Gentofte, Denmark.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: Nanna B
authors.initials: NB
authors.lastname: Johansen
authors.affiliation: Danish Diabetes Academy, Odense, Denmark.|Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.affiliation: Research Department of Epidemiology and Public Health, University College London, London, U.K.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh-Manoux
authors.affiliation: Research Department of Epidemiology and Public Health, University College London, London, U.K.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.affiliation: Research Department of Epidemiology and Public Health, University College London, London, U.K.|1st Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Tabak
authors.affiliation: Research Department of Epidemiology and Public Health, University College London, London, U.K.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brunner
authors.affiliation: Research Department of Epidemiology and Public Health, University College London, London, U.K.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shipley
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008659:Metabolic Diseases / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D008875:Middle Aged; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D012307:Risk Factors; D059289:Vascular Stiffness
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin