It is recommended that individuals with diabetes restrict their dietary sodium intake. However, although salt intake is correlated with BP (blood pressure), it also partly determines the activation state of the RAAS (renin–angiotensin–aldosterone system), a key mediator of diabetes-associated atherosclerosis. apoE KO (apolipoprotein E knockout) mice were allocated for the induction of diabetes with streptozotocin or citrate buffer (controls) and further randomized to isocaloric diets containing 0.05%, 0.3% or 3.1% sodium with or without the ACEi [ACE (angiotensin-converting enzyme) inhibitor] perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis were assessed using RT–PCR (reverse transcription–PCR) and ELISA. The association of sodium intake and adverse cardiovascular and mortality outcomes were explored in 2648 adults with Type 1 diabetes without prior CVD (cardiovascular disease) from the FinnDiane study. A 0.05% sodium diet was associated with increased plaque accumulation in diabetic apoE KO mice, associated with activation of the RAAS. By contrast, a diet containing 3.1% sodium suppressed atherogenesis associated with suppression of the RAAS, with an efficacy comparable with ACE inhibition. In adults with Type 1 diabetes, low sodium intake was also associated with an increased risk of all-cause mortality and new-onset cardiovascular events. However, high sodium intake was also associated with adverse outcomes, leading to a J-shaped relationship overall. Although BP lowering is an important goal for the management of diabetes, off-target actions to activate the RAAS may contribute to an observed lack of protection from cardiovascular complications in patients with Type 1 diabetes with low sodium intake.
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Research Article|
February 04 2013
Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes
Chris Tikellis;
Chris Tikellis
*Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia
†Central Clinical School, Monash University, Melbourne, Australia
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Raelene J. Pickering;
Raelene J. Pickering
*Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia
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Despina Tsorotes;
Despina Tsorotes
*Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia
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Valma Harjutsalo;
Valma Harjutsalo
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Lena Thorn;
Lena Thorn
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Aila Ahola;
Aila Ahola
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Johan Wadén;
Johan Wadén
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Nina Tolonen;
Nina Tolonen
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Markku Saraheimo;
Markku Saraheimo
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Daniel Gordin;
Daniel Gordin
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Carol Forsblom;
Carol Forsblom
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Per-Henrik Groop;
Per-Henrik Groop
*Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
§Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland
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Mark E. Cooper;
Mark E. Cooper
*Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia
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John Moran;
John Moran
∥Department of Intensive Care Medicine, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, South Australia, Australia
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Merlin C. Thomas
*Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia
‡Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
¶Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
Correspondence: Professor Merlin C. Thomas (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 27 2012
Revision Received:
December 06 2012
Accepted:
December 10 2012
Accepted Manuscript online:
December 10 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 124 (10): 617–626.
Article history
Received:
June 27 2012
Revision Received:
December 06 2012
Accepted:
December 10 2012
Accepted Manuscript online:
December 10 2012
Citation
Chris Tikellis, Raelene J. Pickering, Despina Tsorotes, Valma Harjutsalo, Lena Thorn, Aila Ahola, Johan Wadén, Nina Tolonen, Markku Saraheimo, Daniel Gordin, Carol Forsblom, Per-Henrik Groop, Mark E. Cooper, John Moran, Merlin C. Thomas; Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes. Clin Sci (Lond) 1 May 2013; 124 (10): 617–626. doi: https://doi.org/10.1042/CS20120352
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