Sodium Sensitivity Related to Albuminuria Appearing Before Hypertension in Type 2 Diabetic Patients

Imanishi, Masahito; Yoshioka, Katsunobu; Okumura, Michiaki; Konishi, Yoshio; Okada, Noriyuki; Morikawa, Takashi; Satô, Toshihiko; Tanaka, Shiro; Fujii, Satoru

doi:10.2337/diacare.24.1.111

Cited by 53 publications

(43 citation statements)

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“…In agreement with our previous studies, 9 the present study showed that BP was salt sensitive from an early stage in patients with type 2 diabetic nephropathy who had microalbuminuria. The finding that salt sensitivity of BP was associated with reduced urinary excretion of NOx suggests a possible contribution of reduced intrarenal NO bioactivity to the development of salt-dependent hypertension in patients with diabetic nephropathy.…”

Section: Discussionsupporting

confidence: 94%

“…15 Similar results have also been reported in Dahl salt-sensitive hypertensive rats, 16 which show reduced intrarenal NO levels. 5 The present finding that patients with type 2 diabetic nephropathy display reduced urinary excretion of NOx and increased salt sensitivity of BP, combined with results from previous studies, 2,4,7,9,15,16 is consistent with the concept that salt sensitivity of BP is induced by decreased intrarenal NO bioactivity in patients with diabetic nephropathy. We observed that treatment with an ARB restored reduced urinary renal NOx excretion in patients with type 2 diabetic nephropathy and microalbuminuria.…”

Section: Discussionsupporting

confidence: 90%

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Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Imanishi

Okada

Konishi

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Introduction:We have previously demonstrated the increased salt sensitivity of blood pressure (BP) in diabetic patients with early nephropathy. Here, we examined the effects of an angiotensin II receptor blocker (ARB) on salt sensitivity and renal oxidative stress or nitric oxide (NO) in those patients. Patients and methods: Type 2 diabetic patients with (n = 6) and without (n = 6) microalbuminuria were studied on a high-salt diet for one week and on a salt-restricted diet for one week. The study was repeated in the patients with microalbuminuria during treatment with an ARB, valsartan (80 mg/day). Salt sensitivity was assessed from the BP/sodium excretion curve. Urinary excretion rates of NOx, 8-hydroxy-2-deoxyguanosine as a marker of oxidative stress, and plasma tetrahydrobiopterin as a cofactor for NO synthase were measured. Results: Compared with diabetic patients without microalbuminuria, patients with microalbuminuria showed greater salt sensitivity and lower urinary excretion of NOx. In the patients with microalbuminuria, treatment with valsartan reduced salt sensitivity in association with increased NOx excretion, reduced 8-hydroxy-2,-deoxyguanosine excretion, and increased plasma tetrahydrobiopterin levels. Conclusions: These data support the hypothesis that ARBs reduce the salt sensitivity of BP by decreasing renal oxidative stress and restoring NO activity in diabetic patients with microalbuminuria.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 90%

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Imanishi

Okada

Konishi

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…[Diabetologia (2004) 47:300-303] Keywords Microalbuminuria · Salt sensitivity · Type 2 diabetes · Glomerular filtration rate · Renal plasma flow · Intraglomerular pressure · Insulin resistance increased exchangeable sodium pool in diabetic patients [2], few studies have addressed the role of sodium intake on blood pressure and kidney haemodynamics in Type 2 diabetes. Recently it was shown that in Type 1 and in Type 2 diabetic patients with increased albumin excretion the sensitivity of blood pressure to salt intake is greater than in patients with normoalbuminuria [3,4].…”

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confidence: 99%

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

et al. 2003

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Aims/hypothesis. This study was done to measure the effect of Na + intake on blood pressure and albuminuria, in relation with insulin sensitivity and kidney haemodynamics, in Type 2 diabetic patients with and without microalbuminuria. Methods. Type 2 diabetic patients, 20 with microalbuminuria, 21 without, spent two consecutive 7-day periods, one on a high (250 mmol), the other on a low-Na + (20 mmol) diet. Body weight, 24-h blood pressure and albuminuria were measured at the end of each period. At the end of high-Na + diet insulin sensitivity (euglycaemic insulin clamp; 2 mU·kg −1 ·min −1 ) and kidney haemodynamics were measured in nine patients from each group. Results. Switching from low to high-Na + diet resulted in an increase in blood pressure (7.4±4.7 mmHg; p<0.001), body weight (1.9±0.4 kg; p<0.05) and albuminuria [from 80 (31-183) µg/min to 101 (27-965) µg/min; p<0.01) in patients with microalbuminuria. No changes occurred in patients without microalbuminuria. Patients with microalbuminuria also had greater intraglomerular pressure (44±1 mmHg vs 36±1; p<0.001), calculated from glomerular filtration rate, renal plasma flow, plasma protein concentration and the relationship between pressure and natriuresis. In these patients insulin sensitivity was lower (5.16± 49 vs 7.36±0.63 mg·kg −1 ·min −1 ; p=0.007). Urinary albumin excretion (r=0.40; p=0.009) and insulin sensitivity (r=−0.59; p=0.01) were correlated with intraglomerular pressure. Conclusion/interpretation. High salt intake increases blood pressure and albuminuria in Type 2 diabetic patients with microalbuminuria. These responses are associated with insulin resistance and increased glomerular pressure. Insulin resistance could contribute to greater salt sensitivity, increased glomerular pressure and albuminuria. [Diabetologia (2004) 47:300-303]

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“…Blood pressure was measured in the supine position using a sphygmomanometer. Clinical laboratory data were obtained in our institution, as previously reported (13 Nonobstructive disease was defined as a stenosis of 0 -50%. The inter-and intraobserver variability of grading was 8 and 3%, respectively.…”

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Impact of Diabetes on Coronary Stenosis and Coronary Artery Calcification Detected by Electron-Beam Computed Tomography in Symptomatic Patients

et al. 2002

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OBJECTIVE -Ischemic heart disease is a pivotal complication for diabetic patients. Electron-beam computed tomography (EBCT) represents the only noninvasive method that allows for accurate quantification of coronary artery calcification that reflects underlying atherosclerotic disease. Although coronary calcium score (CCS) cut points that predict the presence of angiographic stenosis have been established in nondiabetic individuals, it is not known whether coronary calcifications in diabetic patients are associated with the presence of significant coronary stenoses. In this study, we evaluated the relationship between coronary calcifications and angiographic stenosis in symptomatic patients with or without type 2 diabetes.RESEARCH DESIGN AND METHODS -In this study, 282 patients (204 men and 78 women) with chest pain, including 101 diabetic patients and 181 nondiabetic patients (mean age 63 Ϯ 9.6 years), underwent coronary angiography and EBCT with determination of CCS using Agatston's method. Luminal stenosis Ն50% was defined as significant coronary stenosis. RESULTS -Angiography identified 205 patients with significant stenoses (89 of 101 diabetic patients, 114 of 181 nondiabetic patients). The sensitivity and specificity of EBCT to detect significant coronary stenosis were not significantly different between diabetic and nondiabetic patients. In diabetic patients, a CCS Ն90 was associated with 75% sensitivity and 75% specificity, whereas a CCS Ն200 was associated with 64% sensitivity and 83% specificity.CONCLUSIONS -We demonstrated that calcification of the coronary arteries in symptomatic diabetic patients is well associated with severity of coronary stenosis, as in nondiabetic patients. Diabetes Care 25:696 -701, 2002C ardiovascular disease is the chief cause of morbidity and mortality in diabetic patients (1). Over half of all diabetic patients eventually die from a complication of cardiovascular disease. It has been reported that the 7-year cardiovascular mortality rate among patients with type 2 diabetes without a prior history of myocardial infarction is as high as that in nondiabetic patients with previous infarction (2). This implies that diabetic patients without known infarction may have advanced coronary atherosclerosis. Various screening tests are available to identify patients at high risk for atherosclerotic disease, including exercise electrocardiogram (ECG) testing, thallium myocardial scintigraphy, and stress echo cardiography. However, there is no consensus concerning the appropriate screening test for coronary disease in patients with diabetes. Exercise ECG testing has a relatively high specificity and sensitivity (68 and 77%, respectively) (3), but often diabetic patients cannot perform an exercise test because of complications such as arteriosclerosis obliterans. Thallium scintigraphy also has satisfactory sensitivity and specificity but is expensive to perform.Electron-beam computed tomography (EBCT) can noninvasively and accurately detect coronary calcification, which is a predictor of is...

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Sodium Sensitivity Related to Albuminuria Appearing Before Hypertension in Type 2 Diabetic Patients

Abstract: Abbreviations: ANOVA, analysis of variance; MAP, mean arterial pressure; SSI, sodium sensitivity index; UNaV, urinary sodium excretion.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Cited by 53 publications

References 27 publications

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

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

Impact of Diabetes on Coronary Stenosis and Coronary Artery Calcification Detected by Electron-Beam Computed Tomography in Symptomatic Patients

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