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

• Published in: Diabetes care Vol. 25; no. 4; pp. 663 - 671
• Main Authors: HOULIHAN, Christine A, ALLEN, Terri J, BAXTER, Amynta L, PANANGIOTOPOULOS, Sianna, CASLEY, David J, COOPER, Mark E, JERUMS, George
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-04-2002
• Subjects: Albuminuria; Aldosterone - blood; Angiotensin II - metabolism; Antihypertensive Agents; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure - drug effects; Creatinine - blood; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetics; Diet; Diet, Sodium-Restricted; Drug Synergism; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Food and nutrition; Hemodynamics - drug effects; Hemodynamics - physiology; Hormones. Endocrine system; Humans; Hypertension; Losartan; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Physiological aspects; Placebos; Renal Circulation - drug effects; Renal Circulation - physiology; Renin - blood; Salt-free diet; Sodium; Sodium - urine; Type 2 diabetes; Australia; Endocrinopathy; Ability; Human; Hypertension; Drug; Excretion; Prevalence; Albumin; Cardiovascular disease; Non insulin dependent diabetes; Epidemiology; Kidney; Randomization; Treatment; Diet; Sodium; Losartan; Arterial pressure; Blood pressure; Ambulatory; Hemodynamics
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.25.4.663

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 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.
Footnotes
Address correspondence and reprint requests to Prof. George Jerums, Endocrine Unit, Austin and Repatriation Medical Centre,
Studley Rd., Heidelberg 3084, Victoria, Australia. E-mail: endo{at}austin.unimelb.edu.au .
Received for publication and accepted in revised form.
Abbreviations: ABP, ambulatory blood pressure; ACR, albumin-to-creatinine ratio; AER, albumin excretion rate; ANG, angiotensin; CI, confidence
interval; ERPF, effective renal plasma flow; FF, filtration fraction; GFR, glomerular filtration rate; PAH, para-aminohippurate;
P GC , glomerular capillary pressure; PRA, plasma renin activity; RAS, renin-angiotensin system.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
M.E.C. is on an advisory panel for Merck on diabetic nephropathy, he has received honoraria for speaking engagements for Merck,
and his laboratory has received funding from Merck for studies on a new drug to treat retinopathy.
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