A low-sodium diet potentiates the effects of losartan in type 2 diabetes.
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 microg/min.


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 reduction resulting from the addition of a low-sodium diet to losartan was of similar magnitude to that predicted from the addition of a second antihypertensive agent.
Houlihan
Christine A
CA
Endocrine Unit and Department of Medicine, University of Melbourne, Austin, Australia.
Allen
Terri J
TJ
Baxter
Amynta L
AL
Panangiotopoulos
Sianna
S
Casley
David J
DJ
Cooper
Mark E
ME
Jerums
George
G
D000419:Albuminuria; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism; D000959:Antihypertensive Agents; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004039:Diet, Sodium-Restricted; D004357:Drug Synergism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine
D000959:Antihypertensive Agents; D001786:Blood Glucose; D010919:Placebos; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D003404:Creatinine; D012083:Renin; D019808:Losartan