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

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.
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PMID:Optimizing antihypertensive therapy in patients with diabetic nephropathy. 985 27

We determined the relationship between the gene polymorphism of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), or angiotensin II receptor (AT1R) and the progression of diabetic nephropathy in a multicenter trial of ethnically homogeneous Japanese patients with non-insulin-dependent diabetes (NIDDM). Gene polymorphism of ACE I/D, AGT M235T and AT1R A1166C was determined by polymerase chain reaction amplification using allele-specific primers. Japanese NIDDM patients (n = 1,152) were selected from several diabetic clinics. All patients were divided into three groups as follows: (1) group I (n = 407): normoalbuminuric patients; (2) group II (n = 327): microalbuminuric patients, and (3) group III (n = 418): overt albuminuric patients. Clinical factors for investigation in all patients were the date of birth, gender, levels of urinary albumin excretion, findings of the ocular fundus, duration of diabetes, hemoglobin A1c and blood pressure. It appears that genetic polymorphisms in the renin-angiotensin systems, i.e. ACE or AT1R, may affect the progression to renal failure of patients (especially females) with NIDDM.
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PMID:Relationship between polymorphism in the angiotensinogen, angiotensin-converting enzyme or angiotensin II receptor and renal progression in Japanese NIDDM patients. 1036 6

The prevention and treatment of hypertension remain as major challenges for clinicians all over the world. The recently published Sixth Report of the Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) uses evidence-based medicine in providing guidelines to aid clinicians in the prevention, detection and treatment of high blood pressure, including pharmacological approaches. Calcium antagonists are used widely for the treatment of hypertension, and JNC-VI focuses on specific situations where calcium antagonists could be considered as preferred treatments. There are a large number of calcium antagonists available, with a variety of pharmacodynamic and pharmacokinetic actions. Several sustained-release formulations of these drugs are also available. In terms of blood pressure control, calcium antagonists are more effective as antihypertensive treatments than beta-blockers, ACE inhibitors and angiotensin II receptor blockers in Black patients. The dihydropyridine calcium antagonists have been shown to reduce morbidity and mortality in elderly patients with isolated systolic hypertension. The rate-lowering calcium antagonists can be used as alternatives to beta-blockers in patients with coronary artery disease and hypertension. Calcium antagonists can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus and/or renal disease. Some dihydropyridine calcium antagonists may be useful as alternatives to ACE inhibitors in patients with hypertension and systolic heart failure. Calcium antagonists appear to be extremely useful in patients with cyclosporin-induced hypertension, and in patients with hypertension and concomitant Raynaud's phenomenon and/or migraine. The rate-lowering agents can be used in patients with atrial tachyarrhythmias and hypertension. Clinicians should be aware of drug-drug interactions involving calcium antagonists, especially after the recent problems with mibefradil. Although retrospective studies have caused controversy regarding the safety of calcium antagonists in patients with hypertension, recent prospective studies have revealed no major safety concerns with these drugs.
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PMID:How to use calcium antagonists in hypertension: putting the JNC-VI guidelines into practice. Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 1055 31

Diabetes is associated with alterations in nitric oxide-mediated vasomotor function. The role of nitric oxide generated via the neuronal nitric oxide synthase pathway in the control of systemic and renal hemodynamics in diabetes has not been studied. To explore the hypothesis that diabetic vascular dysfunction is in part caused by altered neuronal nitric oxide synthase activity, systemic and renal hemodynamics were assessed before and after acute inhibition of this enzyme with a specific inhibitor, S-methyl-L-thiocitrulline, in control and diabetic rats. The interaction of this pathway and the renin-angiotensin system was studied in separate groups of rats pretreated with the angiotensin II receptor blocker losartan; these rats were compared with rats treated with losartan alone. Diabetic animals demonstrated higher baseline glomerular filtration rates and filtration fractions. At a low dose, the neuronal nitric oxide synthase inhibitor induced similar dose-dependent pressor responses in control and diabetic rats. Losartan abolished the pressor response in both groups. No changes in renal plasma flow or renal vascular resistance occurred in control rats. In contrast, diabetic rats responded with significant renal vasoconstriction. At a high dose, the renal vasoconstriction was similar in both groups and was not affected by losartan. In conclusion, neuronal nitric oxide synthase-derived nitric oxide plays a role in the control of systemic and renal hemodynamics in normal and diabetic rats. Diabetic rats are more sensitive to the inhibitor, suggesting increased activity of this pathway in the diabetic kidney. Furthermore, renal responses in diabetic rats were attenuated by angiotensin II receptor blockade, whereas losartan alone induced hemodynamic changes that were opposite those seen with neuronal nitric oxide synthase inhibition. This observation implicates angiotensin II as an important modulator of this nitric oxide pathway in diabetes.
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PMID:Effects of systemic inhibition of neuronal nitric oxide synthase in diabetic rats. 1067 13

Hypertension in diabetic patients must be treated aggressively if patients are to benefit from reduced risk of morbidity and mortality. Diabetes itself must be diagnosed promptly, particularly in at-risk patients, so appropriate lifestyle modifications can be made at the earliest opportunity. Although this may reduce or delay onset of hypertension, antihypertensive drug treatment should be initiated in the diabetic patient with even high-normal blood pressure. Traditional approaches to management of hypertension are inappropriate for most patients with diabetes. While ACE inhibitors, calcium antagonists, angiotensin II receptor blockers, beta blockers, and low-dose diuretics, alone or in combination, all currently have roles in hypertension management, the outcomes of studies now under way may clarify some still unanswered questions about the dangerous combination of high blood pressure and diabetes.
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PMID:Hypertension in patients with diabetes. Strategies for drug therapy to reduce complications. 1077 10

The treatment of high-risk hypertensive patients with diabetes presents clinicians with challenges and opportunities. The coexistence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Perhaps most important among these is the increased risk of cardiovascular events in this patient population, an observation that can be best appreciated by the increased number of deaths attributed to cardiovascular-related diseases in diabetic patients aged 45 to 65 years. Consequently, aggressive therapy in this population offers the promise of significantly reducing excess cardiovascular deaths. Despite this opportunity for reducing mortality in these high-risk patients, several challenges to treatment remain. While aggressive blood pressure reduction has been documented to reduce the rate of events in these patients, questions remain as to the level to which blood pressure should be reduced. The recent guidelines from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure emphasized the importance of treating patients with hypertension and diabetes as if they already have target organ damage. Low blood pressure targets of 130/85 mm Hg, with an optimal goal of 120/80 mm Hg, can reduce the risk of events in hypertensive patients with diabetes, regardless of the pharmacological means used. However, there are physiologic and clinical rationale for renin angiotensin system blockade, with angiotensin-converting enzyme inhibition as the preferential therapy in these patients. In this regard, preliminary data with the new class of angiotensin II receptor blockers suggest that these agents may offer benefits equivalent to those observed with angiotensin-converting enzyme inhibitors while offering better tolerance.
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PMID:Hypertension and diabetes: new therapeutic options. 1084 51

Proteinuric nephropathies either of diabetic or nondiabetic origin tend to develop renal structural damage associated with progressive renal function decline over time. In proteinuric glomerular disease excessive protein reabsorption by proximal tubular epithelial cells modulates tubular cell function to the extent that cell growth and their phenotypic expression of growth factors and inflammatory chemokines and cytokines is upregulated. Recent evidence is available that renal tubular cells synthesize endothelins (ETs), a family of peptides with potent vasoconstrictor and proliferation properties, and that overloading these cells with proteins induces a dose-dependent increase in the synthesis and release of ET-1. This peptide, accumulating in the renal interstitium, eventually participates in activation of the sequence of events that leads to interstitial inflammation and ultimately renal scarring. Increased renal synthesis of ET-1 occurs in vivo as documented in several animal models of proteinuric progressive nephropathies, in which enhanced renal ET-1 gene expression as well as the excretion of the peptide in the urine correlated with the urinary protein excretion rate. Similarly, in patients with chronic renal disease an association has been found between increased urinary excretion of ET-1 and renal damage. A strong argument in favor of ET-1 as a mediator of renal injury derives from preclinical studies with selective and non-selective ET receptor antagonists that have became available in the past few years. They block the effect of ET to their specific receptors called ET(A) and ET(B), and have been reported to have a renoprotective effect in several animal models of progressive renal disease, including in rats with remnant kidney or experimental diabetes as well as mice with lupus nephritis. The peptide nature of some of these compounds, which are currently appearing in the literature, may however hamper their future use in humans. Administration of nonpeptide ET receptor antagonists to humans would hopefully overcome this problem and possibly provide a new therapeutic approach for patients with renal disease who do not adequately respond to the currently available therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists.
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PMID:Endothelin antagonists and renal protection. 1097 87

The goals of antihypertensive therapy are to lower blood pressure and prevent end-organ damage without side effects, which affect quality of life. The antihypertensive drugs, regardless of class, all lower blood pressure, but they vary in their mechanisms of action, side-effect profiles, suitability for patients with other comorbid conditions, and ability to protect against the long-term sequelae of hypertension. The Sixth Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure (JNC-VI) recommends diuretics and beta-blockers as first-line therapy for uncomplicated hypertension, with diuretics also being strongly preferred for patients with isolated systolic hypertension or hypertension and heart failure and beta-blockers being strongly preferred for patients who have had a myocardial infarction (MI) and those with hypertension and angina, atrial tachycardia, or atrial fibrillation. Because angiotensin-converting enzyme (ACE) inhibitors have been shown to be cardioprotective and renoprotective in patients with diabetes or impaired left ventricular (LV) function, the JNC-VI recommends them as first-line therapy in patients with diabetes with proteinuria, heart failure, and MI complicated by LV dysfunction. It recommends calcium channel blockers for hypertensive patients with angina, long-acting dihydropyridines for those with isolated systolic hypertension, and the nondihydropyridines for those with atrial tachycardia or fibrillation, diabetes, and proteinuria. The angiotensin II receptor blockers (ARBs) share many of the organ-protective effects of ACE inhibitors when studied in animal models. They are effective in lowering blood pressure and have a very benign side-effect profile; however, these agents have not been available long enough to ascertain their efficacy in protecting against long-term complications.
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PMID:Clinical overview of antihypertensive classes--clinically relevant differences: myths or facts? Based on a presentation by Alan H. Gradman, MD. 1097 60

In this article we emphasize the need for prompt intervention in diabetic patients with high blood pressure in order to protect the heart, brain, kidney, and the vascular tree against arteriosclerotic damage, which is the main cause of mortality in type 1, and particularly type 2 diabetes mellitus. Recent placebo-controlled, randomized trials indicate that compared with the nondiabetic population, a lower blood pressure threshold for intervention and a lower target blood pressure are adequate in terms of target organ protection. Although all major classes of antihypertensive drugs have demonstrated a potential benefit in treating diabetic hypertensive patients, blocking the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors is especially useful in patients at high risk for myocardial infarction and/or renal damage. The new class of antihypertensive agents that block the angiotensin II receptor have renal effects very close to those observed with ACE inhibitors. The potential role of this new class in the treatment of hypertension in diabetes will depend on the results of ongoing trials.
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PMID:Treatment of hypertension in diabetes mellitus. 1098 Nov 68

There is convincing evidence for a specific BP-independent effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 +/- 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 +/- 5.1 yr) with baseline urinary albumin excretion rates (AER) >20 microg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 +/- 7.1 mmHg in the third week of placebo and 91.1 +/- 8.7 mm Hg on moxonidine). There was a significant (P< 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 microg/min (range, 15.9 to 117 microg/min) versus 29.0 (range, 9.03 to 85.8 microg/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for the finding.
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PMID:Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy? 1118 10


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