title: Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes.
abstract: 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.
authors.affiliation: Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Tikellis
authors.forename: Raelene J
authors.initials: RJ
authors.lastname: Pickering
authors.forename: Despina
authors.initials: D
authors.lastname: Tsorotes
authors.forename: Valma
authors.initials: V
authors.lastname: Harjutsalo
authors.forename: Lena
authors.initials: L
authors.lastname: Thorn
authors.forename: Aila
authors.initials: A
authors.lastname: Ahola
authors.forename: Johan
authors.initials: J
authors.lastname: Wadén
authors.forename: Nina
authors.initials: N
authors.lastname: Tolonen
authors.forename: Markku
authors.initials: M
authors.lastname: Saraheimo
authors.forename: Daniel
authors.initials: D
authors.lastname: Gordin
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: John
authors.initials: J
authors.lastname: Moran
authors.forename: Merlin C
authors.initials: MC
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000139:chemically induced*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality; D015331:Cohort Studies; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000401:mortality / Q000652:urine; D004039:Diet, Sodium-Restricted; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D020913:Perindopril; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000517:prevention & control; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001057:Apolipoproteins E; D012982:Sodium, Dietary; D012964:Sodium; D020913:Perindopril