Journal article

Transient Intermittent Hyperglycemia Accelerates Atherosclerosis by Promoting Myelopoiesis

Michelle C Flynn, Michael J Kraakman, Christos Tikellis, Man KS Lee, Nordin MJ Hanssen, Helene L Kammoun, Raelene J Pickering, Dragana Dragoljevic, Annas Al-Sharea, Tessa J Barrett, Fiona Hortle, Frances L Byrne, Ellen Olzomer, Domenica A McCarthy, Casper G Schalkwijk, Josephine M Forbes, Kyle Hoehn, Liza Makowski, Graeme I Lancaster, Assam El-Osta Show all

Circulation Research | LIPPINCOTT WILLIAMS & WILKINS | Published : 2020

Abstract

RATIONALE: Treatment efficacy for diabetes mellitus is largely determined by assessment of HbA1c (glycated hemoglobin A1c) levels, which poorly reflects direct glucose variation. People with prediabetes and diabetes mellitus spend >50% of their time outside the optimal glucose range. These glucose variations, termed transient intermittent hyperglycemia (TIH), appear to be an independent risk factor for cardiovascular disease, but the pathological basis for this association is unclear. OBJECTIVE: To determine whether TIH per se promotes myelopoiesis to produce more monocytes and consequently adversely affects atherosclerosis. METHODS AND RESULTS: To create a mouse model of TIH, we administere..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Dutch Heart Foundation


Awarded by Dutch Diabetes Foundation


Awarded by American Heart Association (AHA) Career Development Award


Awarded by American Heart Association


Awarded by NHMRC fellowship


Awarded by American Heart Association Strategically Focused Research Network in Cardiometabolic Health


Awarded by NIH


Awarded by Career Development Fellowship from the NHMRC


Awarded by National Heart Foundation



Funding Acknowledgements

This work was supported by an National Health and Medical Research Council (NHMRC) grant (APP1106154) to A.J. Murphy and M.C. Thomas. M.J. Kraakman is a Russell Berrie Foundation Scholar in Diabetes Research from the Naomi Berrie Diabetes Centre. N.M.J. Hanssen is supported by the Dutch Heart Foundation (2017T039), Dutch Diabetes Foundation (2017.85.005), and the European Foundation for the Study of Diabetes (EFSD). T.J. Barrett is supported by an American Heart Association (AHA) Career Development Award (18CDA34110203AHA). L. Makowski was funded by American Heart Association 13BGIA17070106 and University of Tennessee Health Science Center (UTHSC) Methodist Mission Support Fund. J.M. Forbes is supported by an NHMRC fellowship (APP1102935) and the Mater Foundation. E.A. Fisher was funded by the NIH P01 HL131481. I.J. Goldberg is supported by grants HL45095 and HL73029 and American Heart Association Strategically Focused Research Network (35210245) in Cardiometabolic Health. A. El-Osta is an NHMRC Senior Research Fellow (APP1154650). P.R. Nagareddy is supported by grants from the NIH (R01HL137799 and R00HL122505). A.J. Murphy is supported by Career Development Fellowship from the NHMRC (APP1085752), a Future Leader Fellowship from the National Heart Foundation (100440), a Viertel Award from Diabetes Australia Research Trust, and a Centenary Award from Commonwealth Serum Laboratories (CSL).