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

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 g/min.RESEARCH DESIGN AND METHODS -In this study, 20 subjects were randomized to losartan 50 mg/day (n ϭ 10) or placebo (n ϭ 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 Ϯ 14 and 80 Ϯ 22 mmol/day in the losartan and placebo groups, respectively. In the losartan group, the additional blood pressureϪlowering effects of a low-sodium diet compared with a regularsodium diet for 24-h systolic, diastolic, and mean arterial blood pressures were 9.7 mmHg (95% confidence interval [CI], 2.2Ϫ17.2; P ϭ 0.002), 5.5 mmHg (2.6Ϫ8.4; P ϭ 0.002), and 7.3 mmHg (3.3Ϫ11.3; P ϭ 0.003), respectively. In the losartan group, the ACR decreased significantly on a low-sodium diet versus on a regular-sodium diet (Ϫ29% [CI Ϫ50.0 to Ϫ8.5%] vs. ϩ14% [Ϫ19.4 to 47.9%], respectively; P ϭ 0.02). There was a strong correlation between fall in blood pressure and percent reduction in the ACR (r ϭ 0.7, P ϭ 0.02). In the placebo group, there were no significant changes in blood pressure or ACR between regularand 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. Diabetes Care 25:663-671, 2002H igh blood pressure is an important modifiable risk factor in preventing diabetic micro-and macrovascular complications. Subjects with diabetes have a high prevalence of hypertension and often require multiple antihypertensive agents to achieve blood pressure targets (1).The role of ACE inhibitors in the prevention and treatment of diabetic nephropathy is well established in patients with type 2 (2) and type 1 diabetes (3). More recently, blockade of the reninangiotensin system (RAS) with angiotensin (ANG)-II receptor antagonists has been shown to attenuate the rate of progression of renal dysfunction in patients with type 2 diabetes (4,5).In nondiabetic subjects with renal disease, the antiproteinuric effects of ACE inhibitors strongly depend on dietary sodium intake (6). Furthermore, the antihypertensive effects of ANG-II receptor antagonists have shown dependence on the baseline activation of the RAS in nondiabetic patients (7). In...

Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance

“…Our results provide further support for encouraging Type 2 diabetic patients with microalbuminuria to reduce salt intake, because such a reduction could help preserve renal function, especially when associated with ACE-inhibition treatment, as recently shown [9]. Our data provide insights into the potential mechanisms of the beneficial effects of low-dose diuretic therapy, alone or in combination with ACE-inhibitors in the treatment of hypertension and microalbuminuria in diabetes [10].…”

Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy

“…However, blockade of the RAS alone, both experimentally and clinically, only retards but does not prevent or reverse diabetic nephropathy [6,9]. Furthermore, it has been postulated that the effects of blockade of the RAS could be limited by the salt and water retention often found in experimental and clinical diabetes [10,11].…”

Effects of Intensive Low-Salt Diet Education on Albuminuria among Nondiabetic Patients with Hypertension Treated with Olmesartan

“…Low salt intake is associated with favorable effects on albuminuria, BP, and GFR (11)(12)(13). High salt intake enhances the generation of superoxide anion accompanied by enhanced renal expression and nicotinamide dehydrogenase activation.…”

“…Several studies revealed an additive effect of dietary salt restriction with RAAS blockade on BP and proteinuria. However, most of these studies include a small number of patients (6,(9)(10)(11)20), and there has been no randomized, controlled study in Korean populations. Most importantly, the methods for implementing LSDs or high-salt diets used in previous studies offered strongly controlled or modulated diets (6,11), or they provided salt tablets (9), which are not suitable for application in typical clinical practice.…”

“…Blockade of the reninangiotensin-aldosterone system (RAAS) is well known to reduce urinary albumin excretion, and it is considered a mainstay of therapy in the prevention of ESRD (4,5). The antiproteinuric effect of the RAAS blockade can be magnified or reduced depending on the amount of dietary salt intake (6)(7)(8)(9)(10)(11).…”