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

The relationship between the renin-angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS.
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PMID:The renin-angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerations. 1287 87

Patients with diabetes mellitus are often associated with hypertension. Hypertension increases the incidence of cardiovascular disease and accelerates the progression of diabetic nephropathy. Japanese Society of Hypertension made own guidelines for the management of hypertension(JSH2000) in 2000. Diabetics are stratified into the high risk group irrespective of their blood pressure levels. Target blood pressure is less than 130/85 mmHg. Hypotensive agents will be initiated at more than 140/90 mmHg along with glycemic control and lifestyle modification. When their blood pressure is within the high normal(130-139/85-89 mmHg), lifestyle modification as well as glycemic control will be initiated. If their blood pressure is not lowered to less than 130/85 mmHg during the next 3-6 months, hypotensive agents will be started. ACEIs, Ca-antagonists and alpha-blockers will be the first line hypotensive agents, since these hypotensive agents improve organ damages and insulin sensitivity and do not worsen lipid metabolisms. Recent guideline made by Japan Diabetes Society in 2003 lowered the target blood pressure furthermore to less than 130/80 mmHg and added angiotensin receptor blockers as one of the firstline hypotensive agents.
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PMID:[Guidelines for the treatment of hypertension in diabetics]. 1287 84

Several factors have contributed to induce the impairment of glucose tolerance in the elderly. Especially, the changes of body composition with aging, the loss of skeletal muscle mass and relatively increased fat tissues, could occur the insulin resistant state. Such states would be well known to accompany with diabetes mellitus and hypertension. Therefore, the treatment of hypertension with diabetes in the elderly could be very important to prevent not only microangiopathy but also macroangiopathy. The optimal blood pressure levels to reduce hypertension-related morbidity and mortality in diabetic elderly have been proposed 130/85 in JSH2000. The first step therapy in this case would be recommended calcium channel blocker, angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. In addition, comprehensive geriatric assessment must be important to maintain drug compliance for well-controlled blood pressure levels.
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PMID:[Treatment of hypertension with diabetes mellitus in the elderly]. 1287 93

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of beta-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. beta-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with beta-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation beta-blocker. Prophylactic utilization of ACE inhibitors and beta-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.
Diabetes Care 2003 Aug
PMID:Heart failure: the frequent, forgotten, and often fatal complication of diabetes. 1288 75

When added to antihypertensive treatment in patients with diabetes and nephropathy, neither the angiotensin receptor blocker (ARB) irbesartan nor the calcium channel blocker amlodipine reduced the overall occurrence of cardiovascular events. However, irbesartan decreased the rate of heart failure and amlodipine reduced the rate of acute myocardial infarction.
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PMID:Do irbesartan and amlodipine reduce cardiovascular events in diabetic patients? 1266 24

Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of this study was to evaluate the effects of renin-anigiotensin system blockage, either by angiotensin-converting enzyme inhibition or angiotensin receptor blockage, on oxidative stress and nitric oxide release in diabetic rat kidneys. After induction of diabetes, six rats were given captopril, six rats were given losartan, and six rats served as diabetic controls. Six healthy rats were also included. At the end of an 8-week period nitric oxide release, lipid peroxidation and protein oxidation were measured in kidney cortices, and urinary albumin excretion (UAE) was determined in 24-h urine samples. Losartan- and captopril-treated diabetic rats had lower levels of UAE than diabetic controls. Diabetic rats had higher levels of lipid peroxidation and protein oxidation compared to healthy rats. NO release was significantly lower in diabetic groups than healthy controls. UAE levels showed a positive correlation with lipid peroxidation and a negative correlation with NO release. Inhibition of lipid peroxidation could be one of the protective mechanisms of renin-angiotensin axis inhibition in diabetic kidney tissues.
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PMID:Effects of captopril and losartan on lipid peroxidation, protein oxidation and nitric oxide release in diabetic rat kidney. 1290 31

We attempted to determine the percentage of patients meeting Health Plan Employer Data Information Set (HEDIS) criteria for blood pressure control (< or = 140/90 mm Hg), to identify factors contributing to differences in blood pressure control among those who met HEDIS criteria and those who did not, and to assess compliance with blood pressure management recommendations established by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) for diabetes mellitus and myocardial infarction. In this retrospective analysis, we randomly selected 502 patient records from three primary care clinics in southeast Michigan. All patients were commercial members of one health maintenance organization, 74% of whom met HEDIS criteria for blood pressure control. These patients took fewer blood pressure drugs throughout the year (p=0.023) and had lower antihypertensive drug costs than those who did not achieve HEDIS blood pressure goals (p=0.016). According to JNC-VI criteria, 46% of diabetic patients were at their blood pressure goal of below 130/85 mm Hg and 71.6% were managed with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Eighty-five percent of patients were taking beta-blockers after myocardial infarction. The percentage of patients achieving target blood pressure exceeded the national average and was associated with few antihypertensive drugs and low drug cost. Effective and appropriate management of blood pressure in people with diabetes remains a challenge.
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PMID:Assessment of factors influencing blood pressure control in a managed care population. 1292 Dec 52

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), two drug classes that effectively block the actions of the renin-angiotensin system (RAS), have unique capabilities as antihypertensive agents. Recent landmark clinical trials have demonstrated their important roles as primary therapy for the prevention of renal disease in diabetes. The optimal dosage of these RAS blockers required to slow the progression of renal disease or impair the development of cardiovascular risk is not known. However, data from many studies strongly support the use of the higher doses of ACE inhibitors or ARBs to reduce proteinuria. All studies of kidney disease progression demonstrate benefit on slowing only when blood pressure is reduced when using higher doses. In order to accrue the optimum benefit from ACE inhibitors and ARBs, the dose-response relationship for diabetic renal disease will have to be determined. The best strategy, ie, supramaximal doses of ACE inhibitors or ARBs or combining them, is still a matter of debate but may be resolved soon by results of ongoing studies.
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PMID:How high should an ACE inhibitor or angiotensin receptor blocker be dosed in patients with diabetic nephropathy? 1294 35

The foundation of treatment for patients with hypertension is ongoing use of lifestyle measures such as physical exercise, weight reduction, and salt restriction. There should be emphasis on reduction of total cardiovascular risk, including smoking cessation and achievement of goal blood pressures. There are now five classes of first-line blood-pressure-lowering drugs - diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium antagonists. In most patients, the choice of drug will be guided by the clinical situation in the individual patient, including the presence of target organ damage, diabetes, established vascular or kidney disease, or other comorbidities. In the absence of such clinical indications, start drug therapy with a low-dose diuretic. Combination therapy will be needed in around two-thirds of patients, and a diuretic will normally form one element of most combinations, with the second or third drug coming from among the remaining four. Consider the use of fixed-dose combinations to improve adherence to therapy. Use long-acting, once-daily preparations.
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PMID:Lowering blood pressure in 2003. 1296 14

In view of the pro-oxidant and proinflammatory effects of angiotensin II, we have tested the hypothesis that valsartan, an angiotensin receptor blocker, may exert a suppressive action on reactive oxygen species (ROS) generation, nuclear factor kappa B (NF-kappa B) in mononuclear cells. Four groups of eight normal subjects were given 1) 160 mg daily of valsartan, 2) 80 mg daily of simvastatin, 3) 40 mg quinapril, or 4) no treatment. Fasting blood samples were obtained before treatment and at d 1, 8, and 14 (7 d after the cessation of the drug). After valsartan, ROS generation by polymorphonuclear cells and mononuclear cells fell significantly by more than 40% (P < 0.01). NF-kappa B binding activity and the expression of total cellular p65, a protein component of NF-kappa B, fell significantly (P < 0.01). The expression of inhibitor kappa B (I kappa B) increased significantly (P < 0.05). Plasma C-reactive protein (CRP) concentration fell significantly (P < 0.01). All indices, except I kappa B, reverted toward baseline, 7 d after the cessation of the drug. I kappa B persisted in an elevated state. Neither quinapril nor simvastatin given for 7 d produced a suppression of ROS generation, intranuclear NF-kappa B, p65, or CRP, and these two agents did not alter cellular I kappa B either. The untreated controls also did not demonstrate a change in their ROS generation or NF-kappa B binding activity or plasma CRP concentration. We conclude that valsartan at a modest dose exerts a profound and rapid ROS and inflammation-suppressive effect that may be relevant to its potential beneficial effects in atherosclerosis, diabetes, and congestive cardiac failure. In contrast, quinapril and simvastatin produced no similar effect over the period of 1 wk. Our observations may also have implications to clinical situations in which a rapid antiinflammatory effect is required.
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PMID:Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: evidence of an antiinflammatory action. 1297 Mar 29


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