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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a nutritional-hygienic disease. Long-term caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria >1 g/d. Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels <130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality.
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PMID:Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. 1281 10

Mineralocorticoid receptor (MR) blockade is effective in reducing total mortality and the incidence of heart failure in patients with systolic left ventricular dysfunction (SLVD) associated with chronic heart failure or post myocardial infarction. Pre-clinical and clinical studies in SLVD have shown that MR blockade reduces sudden cardiac death, left ventricular remodelling, left ventricular hypertrophy, endothelial dysfunction, autonomic imbalance, renal dysfunction and improves fibrinolysis. While MR blockade promotes sodium excretion and the combination of an angiotensin-converting enzyme inhibitor and a MR blocker have been shown to be more effective than either alone in causing natriuresis, it is unlikely that their beneficial effects can be explained solely on this basis. Aldosterone has been shown to have a number of adverse effects, including activation of other neurohumeral mediators, stimulation of active reactive oxygen species (ROS), activation of the NF-Greek small letter kappa kappabeta and AP-1 signalling pathways, vascular inflammation and fibrosis, myocardial hypertrophy, autonomic imbalance, and a decrease in fibrinolysis. MR blockade is, however, effective both in situations with and without an increase in serum aldosterone level, since the MR can be occupied and activated by cortisol as well as by aldosterone. In view of these mechanisms, MR blockade may play an important role not only on SLVD, but also in essential hypertension with normal systolic function, diastolic heart failure, valvular heart disease, vascular stiffening with ageing, progression of renal disease, and diabetes mellitus. This hypothesis will, however, require further prospective evaluation.
J Renin Angiotensin Aldosterone Syst 2003 Sep
PMID:Mineralocorticoid receptor blockade: new insights into the mechanism of action in patients with cardiovascular disease. 1460 20

The development of new-onset diabetes is frequent during the follow-up of treated hypertensive patients. The prevalence of such an event seems to differ depending on the type of antihypertensive therapy used to control blood pressure. Diuretics and b-blockers and their association are particularly harmful in this regard. On the contrary, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, alone or in association with diuretics, are associated with a lower prevalence of this metabolic complication. These statements are confirmed by data from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study. Long-term studies are required to determine the relevance of development of new-onset diabetes in treated hypertensive patients.
J Renin Angiotensin Aldosterone Syst 2003 Sep
PMID:New-onset diabetes and antihypertensive therapy: comments on ALLHAT trial. 1460 21

Left ventricular systolic dysfunction is associated with neurohormonal activation which contributes to progressive ventricular remodeling and worsening clinical heart failure. Renin-angiotensin-aldosterone and sympathetic nervous systems are activated, not only in patients with clinically overt heart failure, but also in patients with asymptomatic or minimally symptomatic left ventricular systolic dysfunction. Activation of the angiotensin and adrenergic systems produces deleterious effects on systemic and coronary hemodynamics, promotes myocyte hypertrophy and fibroblast growth, and myocyte necrosis and apoptosis. Thus, therapy of heart failure should consist of pharmacologic agents not only to relieve symptoms but also to prevent and attenuate ventricular remodeling and progressive heart failure, thereby improving prognosis. In patients who are symptomatic, ACE inhibitors along with digitalis and diuretics as initial therapy (triple therapy) have the greater potential to improve exercise tolerance and decrease the incidence of treatment failure compared with diuretics alone or a combination of diuretics and digitalis. Diuretics alone should not be considered for long-term therapy as plasma renin activity, angiotensin II, aldosterone, norepinephrine and vasopressin levels may increase. ACE inhibitors decrease mortality in patients with heart failure resulting from left ventricular systolic dysfunction. The results of presently available studies indicate that angiotensin II receptor blockers (ARBs) do not provide any advantage over ACE inhibitors regarding survival benefit but may be better tolerated. Long-term adrenergic inhibition with the use of ss-adrenoceptor antagonists added to ACE inhibitors is associated with attenuation of ventricular remodeling, improvement in ventricular function and clinical class and survival of patients with symptomatic systolic left ventricular failure. Thus, initial pharmacotherapy for systolic heart failure should consist of: maximal tolerated dosages of ACE inhibitors;ARBs if ACE inhibitors are not tolerated because of intractable cough or angioedema;adequate dosages of hydralazine and isosorbide dinitrate if ACE inhibitors or ARBs are not tolerated; relatively low dosages of digoxin (serum concentrations of < or = 1.0 ng/dl) if not contraindicated; and diuretics to relieve congestive symptoms. Addition of spironolactone to ACE inhibitors can result in a significant reduction in the risk of sudden death in patients with symptomatic severe heart failure. Myocardial infarction resulting from ischemic heart disease is the most common cause of systolic left ventricular failure and the therapeutic modalities with potential to reduce the risks of myocardial infraction, such as risk factor modification, adequate control of diabetes and hypertension, antiplatelet agents and lipid-lowering agents, should also be included in the initial therapy.
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PMID:Congestive heart failure: what should be the initial therapy and why? 1472 93

The renin-angiotensin system (RAS) is compartmented between circulating blood and tissue pericellular space. Whereas renin and its substrate diffuse easily from one compartment to another, the angiotensin peptides act in the compartment where there are generated: blood or pericellular space. Renin is trapped in tissues by low and high affinity receptors. In the target cells, angiotensin II/AT1 receptor interaction generates different signals including an immediate functional calcium-dependent response, secondary hypertrophy and a late proinflammatory and procoagulant response. These late pathological effects are mediated by NADPH oxydase-generated free oxygen radicals and NFkappaB activation. In vivo, the tissue binding of renin and the induction of converting enzyme are the main determinants of the involvement of the RAS in vascular remodeling. The target cells of interstitial angiotensin II are mainly the vascular smooth muscle cells and fibroblasts, whereas the endothelial cells and circulating leukocytes are the main targets of circulating angiotensin II. In vivo, angiotensin II participates in the vascular wall hypertrophy associated with hypertension. In diabetes, as in other localized fibrotic cardiovascular diseases, the tissue effects of angiotensin II are mainly dependent on its ability to induce TGF-beta expression. In experimental atherosclerosis, angiotensin II infusion induces aneurysm formation mediated by activation of circulating leucocytes. In these models, the administration of angiotensin II antagonists has beneficial effects on pathological remodeling. Such beneficial effects of angiotensin II antagonists in localized pathological remodeling have not yet been demonstrated in humans.
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PMID:[Renin-angiotensin system and vascular remodelling]. 1512 12

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial compared coronary heart disease outcome in two anti-hypertensive treatment strategies based on either an angiotensin receptor blocker, valsartan, or a calcium channel blocker (CCB), amlodipine. In both patient groups a diuretic was added, if necessary, in an attempt to achieve blood pressure (BP) goals. Follow-up of over 15,000 patients was maintained for 4.2 years. There were no differences in the primary composite endpoint of cardiac morbidity and mortality (which included interventional procedures, hospitalised heart failure, non-fatal myocardial infarction and fatal coronary heart disease, however myocardial infarction and stroke events occurred less commonly on amlodipine than on valsartan the former achieving statistical significance [p=0.02 and p=0.08 respectively]). There was a non-significant excess of hospitalised heart failure on amlodipine (p=0.012). However, lower BPs early in the trial probably accounted for most of the observed benefits in favour of the CCB. The angiotensin receptor blocker arm was associated with less new onset diabetes. The results of VALUE add further support to the evidence that blood pressure control is the major determinant in outcome in trials of antihypertensive therapy.
J Renin Angiotensin Aldosterone Syst 2004 Sep
PMID:The VALUE trial: a commentary. 1552 43

Renin angiotensin system inhibitor therapy is seldom offered to individuals who have diabetes and advanced chronic kidney disease because of safety concerns. In this post hoc, secondary analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, angiotensin antagonism risk/benefit profile was assessed in 1513 individuals with type 2 diabetes and overt nephropathy. Incidence of ESRD, hospitalizations for heart failure, withdrawals for adverse events, and proteinuria during losartan or conventional treatment were compared within three tertiles of baseline serum creatinine concentration (highest, 2.1 to 3.6 mg/dl; middle, 1.6 to 2.0 mg/dl; lowest, 0.9 to 1.6 mg/dl). Losartan decreased the risk of ESRD by 24.6, 26.3, and 35.3% in highest, middle, and lowest tertiles, respectively. For every 100 patients with serum creatinine >2.0, 1.6 to 2.0, or <1.6 mg/dl, respectively, 4 yr of losartan therapy was estimated to save 18.9, 8.4, and 2.9 ESRD events and US$1,502,855, US$1,021,770, and US$528,591 costs for renal replacement therapy. Losartan also decreased the hospitalizations for heart failure by 50.2 and 45.1, in the highest and middle tertile, respectively. Withdrawals for adverse events other than heart failure were comparable between tertiles and treatment groups. Proteinuria decreased more on losartan than on placebo in all tertiles (highest, 24 versus -8%; middle, 16 versus -8%; lowest, 15 versus -10%). In proteinuric individuals with type 2 diabetes, losartan therapy reduced ESRD and hospitalizations for heart failure and was well tolerated at all levels of renal function. Angiotensin II antagonism is a suitable and well-tolerated treatment for individuals with type 2 diabetes even with GFR levels approaching renal replacement therapy.
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PMID:Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results. 1557 15

The renin-angiotensin system (RAS) is compartmented between the circulating blood and pericellular spaces. Whereas renin and its substrate diffuse easily from one compartment to another, angiotensin peptides act in the compartment where there are generated. Renin is trapped in tissues by low- and high-affinity receptors. In target cells, angiotensin II/AT1 receptor interaction generates various signals, including an immediate functional calcium-dependent response, secondary hypertrophy, and a late proinflammatory and procoagulant response. These late pathological effects are mediated by NADPH oxidase-generated oxygen free radicals and NF-k-B activation. In vivo, renin tissue binding and converting-enzyme induction are the main determinants of RAS involvement in vascular remodeling. The main target cells of interstitial angiotensin II are vascular smooth muscle cells and fibroblasts, whereas endothelial cells and circulating leukocytes are the main targets of circulating angiotensin II. In vivo, angiotensin II participates in the vascular wall hypertrophy associated with hypertension. In diabetes, as in other localized fibrotic cardiovascular diseases, the tissular effects of angiotensin II are mainly dependent on its ability to induce TGF-beta expression. In experimental atherosclerosis, angiotensin II infusion induces aneurysm formation mediated by activation of circulating leucocytes. Angiotensin II antagonist therapy has beneficial effects on pathological remodeling in animal models, but it remains to be determined whether this is also the case in humans.
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PMID:[Tissue consequence of renin-angiotensin system activation]. 1558 80

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.
Diabetes 2005 Feb
PMID:The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin System Study. 1567 11

Renin-angiotensin system activation is recognized to play an important role in atherosclerosis. This study aimed to verify the antiatherosclerotic effects of ACE inhibition on an experimental model of diabetes and hypercholesterolemia. Diabetes was induced in New Zealand male rabbits with a single dose of alloxan (100 mg/kg, i.v.), and, according to plasma glucose levels obtained after 1 week, the animals were divided into 2 groups (> or =250 mg/dL or <250 mg/dL). Each group was randomly assigned to receive or not quinapril (30 mg/d) added to a 0.5% cholesterol-enriched diet. Animals with high glucose levels at 1 week and that remained high after 12 weeks presented higher triglyceride levels (P < 0.02 versus basal). Those initially hyperglycemic but presenting <250 mg/dL glucose at the end of study formed an additional group. Plasma ACE activity was lower in quinapril-treated animals (P < 0.01 versus untreated groups). However, aorta intima/media ratio and intima area were lower only in the subgroups of quinapril-treated animals with low glucose levels (P < 0.05). Our results support the hypothesis that high plasma glucose may abolish the antiatherosclerotic effect of ACE inhibitors.
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PMID:High glucose levels abolish antiatherosclerotic benefits of ACE inhibition in alloxan-induced diabetes in rabbits. 1577 16


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