Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

CONTEXT: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. OBJECTIVE: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. DESIGN: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. SETTING: Academic clinical research center. PARTICIPANTS: Healthy, nondiabetic, normotensive volunteers. INTERVENTIONS: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5-7 days. MAIN OUTCOME MEASURES: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. RESULTS: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (-16.0 ± 5.6%; P = .007) and C-peptide responses (-21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (-1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. CONCLUSIONS: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity.