Nondiabetic Glucometabolic Status and Progression of Aortic Stiffness: The Whitehall II Study
American Diabetes Association
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McEniery, C., Wilkinson, I., Johansen, N., Witte, D., Singh-Manoux, A., Kivimaki, M., Tabak, A., et al. (2017). Nondiabetic Glucometabolic Status and Progression of Aortic Stiffness: The Whitehall II Study. Diabetes Care, 40 (4), 599-606. https://doi.org/10.2337/dc16-1773
OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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). HbA1c and HOMA-IR were associated with progression of cfPWV after adjusting for physiological confounders and cardiovascular risk factors. A 1 SD higher HbA1c and 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. CONCLUSIONS HbA1c is 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.
aortic stiffening, pulse wave velocity, glucometabolic status, cardiovascular risk factors
This work was supported by the British Heart Foundation (RG/13/2/30098), British Medical Research Council (K013351), the British Department of Health, the British Stroke Association (TSA 2008/05), the US National Heart, Lung, and Blood Institute (R01HL036310), and the US National Institute on Aging (R01AG013196 and R01AG034454). C.M. McEniery and I.B. Wilkinson receive support from the National Institute for Health Research Cambridge Biomedical Research Centre, and the British Heart Foundation Centre of Excellence. I.B. Wilkinson is a British Heart Foundation Senior Fellow. Daniel R. Witte and Nanna B. Johansen are supported by the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. Mika Kivimaki is supported by the Medical Research Council, the Economic and Social Research Council and NordForsk, the Nordic Programme on Health and Welfare and Martin Shipley is partially supported by the British Heart Foundation.
British Heart Foundation (FS/12/8/29377)
External DOI: https://doi.org/10.2337/dc16-1773
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263198