A Low-Sodium Diet Potentiates the Effects of Losartan in Type 2 Diabetes

A Low-Sodium Diet Potentiates the Effects of Losartan in Type 2 Diabetes Christine A. Houlihan , MBBS 1 , Terri J. Allen , PHD 1 , Amynta L. Baxter , BSC, MHN 1 , Sianna Panangiotopoulos , PHD 1 , David J. Casley , M APP SC 2 , Mark E. Cooper , MBBS, PHD 1 and George Jerums , MBBS, MD 1 1 Endocrine Unit and Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia 2 Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia Abstract OBJECTIVE —Diabetic subjects have a high prevalence of hypertension, increased total body exchangeable sodium levels, and an impaired ability to excrete a sodium load. This study assessed the effect of dietary sodium restriction on the efficacy of losartan in hypertensive subjects with type 2 diabetes and albumin excretion rates of 10–200 μg/min. RESEARCH DESIGN AND METHODS —In this study, 20 subjects were randomized to losartan 50 mg/day ( n = 10) or placebo ( n = 10). Drug therapy was given in two 4-week phases separated by a washout period. In the last 2 weeks of each phase, patients were assigned to low- or regular-sodium diets, in random order. In each phase, 24-h ambulatory blood pressure, urinary albumin-to-creatinine ratio (ACR), and renal hemodynamics were measured. RESULTS —Achieved urinary sodium on a low-sodium diet was 85 ± 14 and 80 ± 22 mmol/day in the losartan and placebo groups, respectively. In the losartan group, the additional blood pressure-lowering effects of a low-sodium diet compared with a regular-sodium diet for 24-h systolic, diastolic, and mean arterial blood pressures were 9.7 mmHg (95% confidence interval [CI], 2.2−17.2; P = 0.002), 5.5 mmHg (2.6−8.4; P = 0.002), and 7.3 mmHg (3.3− 11.3; P = 0.003), respectively. In the losartan group, the ACR decreased significantly on a low-sodium diet versus on a regular-sodium diet (−29% [CI −50.0 to −8.5%] vs. + 14% [−19.4 to 47.9%], respectively; P = 0.02). There was a strong correlation between fall in blood pressure and percent reduction in the ACR ( r = 0.7, P = 0.02). In the placebo group, there were no significant changes in blood pressure or ACR between regular- and low-sodium diets. There were no significant changes in renal hemodynamics in either group. CONCLUSIONS —These data demonstrated that a low-sodium diet potentiates the antihypertensive and antiproteinuric effects of losartan in type 2 diabetes. The blood pressure reduct