The association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with type 1 diabetes.
AIMS: It is recommended that individuals with diabetes restrict their dietary sodium intake. But while salt intake is correlated with blood pressure, it also partly determines the activation state of renin-angiotensin-aldosterone-system (RAAS), a key mediator of diabetes-associated atherosclerosis. METHODS: ApolipoproteinE KO 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 ACE inhibitor, perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis assessed using RT-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 cardiovascular disease from the FinnDiane study. RESULTS: 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 to 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. CONCLUSIONS: While blood pressure 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.