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Query: UMLS:C0011860 (type 2 diabetes)
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Angiotensin receptor blockers are a new class of agents that have made a major contribution to the treatment of hypertension. These agents effectively reduce blood pressure and are well tolerated. Other clinical trials have focused, however, on the much wider use of angiotensin receptor blockers in conditions such as congestive heart failure, postmyocardial infarction management, and diabetic nephropathy. Recent studies have provided evidence that these agents might confer target organ protection in hypertension that is equal to, and possibly better than, the benefits provided by conventional antihypertensive agents. Moreover, there is now little doubt that these drugs are effective alternatives to ACE inhibitors in heart failure and will become treatments of choice for patients with type 2 diabetes and nephropathy. Cardiovascular study outcomes have still not determined, however, whether high-risk patients would do better on angiotensin receptor blockers or angiotensin converting enzyme (ACE) inhibitors or a combination of both, except in cases of intolerance to ACE inhibitors.
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PMID:The angiotensin II receptor blockers: opportunities across the spectrum of cardiovascular disease. 1255 52

Type II diabetes mellitus is associated with congestive heart failure with preserved ejection fraction. This group of patients has been assumed to have isolated diastolic dysfunction; however, the longitudinal systolic contraction of the left ventricle has not been studied previously. The objective of the present study was to investigate the longitudinal contraction of the left ventricle in normotensive Type II diabetes mellitus patients with normal ejection fraction. We examined 32 normotensive patients with Type II diabetes mellitus with ejection fraction >0.55 and fractional shortening >0.25. Exclusion criteria were angina pectoris, cardiac valve disease, albuminuria, retinopathy or neuropathy. Normal subjects (n =32) served as controls. A 16 segment model of motion amplitude assessed left ventricular longitudinal contraction and the average of the segments was calculated as the tissue tracking score index. Peak systolic velocity and strain rate was also obtained in each segment. Patients with Type II diabetes mellitus had a significantly lower tissue tracking score index compared with normal subjects (5.8+/-1.6 mm compared with 7.7+/-1.1 mm; P <0.001). Mean peak systolic velocity was also significantly lower (4.3+/-1.5 cm/s compared with 5.4+/-1.0 cm/s; P <0.001), as well as peak systolic strain rate (-1.2+/-0.3 s(-1) compared with -1.6+/-0.4 s(-1); P <0.001). Patients with Type II diabetes mellitus and preserved diastolic function had a significantly lower tissue tracking score index compared with normal subjects (6.6+/-1.5 mm; P <0.001), but patients with diastolic dysfunction had an even more profound decrease in tissue tracking score index compared with patients without diastolic dysfunction (4.9+/-0.9 mm; P <0.01). In conclusion, the longitudinal systolic contraction was significantly decreased in normotensive patients with Type II diabetes mellitus with normal ejection fraction, which was most profound in patients with concomitant diastolic dysfunction.
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PMID:Decreased left ventricular longitudinal contraction in normotensive and normoalbuminuric patients with Type II diabetes mellitus: a Doppler tissue tracking and strain rate echocardiography study. 1263 18

The goal of antihypertensive therapy is to provide effective treatment that can be sustained lifelong, while lowering elevated blood pressure and preventing hypertensive end-organ damage and mortality. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (AIIAs) control blood pressure as well as other available classes of antihypertensive drugs. The ACE inhibitors have been demonstrated to reduce the incidence of stroke, reverse left ventricular hypertrophy, and improve congestive heart failure symptomatology and mortality to a similar degree as diuretics and beta-adrenergic blockers. ACE inhibitors reduce postmyocardial infarction recurrence, improve congestive heart failure symptomatology and mortality, and slow the progression of glomerular renal disease. The AIIAs reverse left ventricular hypertrophy. Several of these agents have been shown to improve congestive heart failure symptomology and mortality, to reduce the occurrence of early atherosclerotic vascular disease, and to slow the progression of renal failure in type 2 diabetes mellitus nephropathy. One AIIA has reduced the incidence of end-stage renal disease in non-insulin-dependence diabetes mellitus nephropathy over 3 years. Ideally, antihypertensive therapy should maintain or improve the patients quality of life without creating side effects or adverse laboratory effects. Among the available nine classes of antihypertensive drugs, ACE inhibitors and the AIIAs come close to meeting the description of an ideal drug. AIIAs and ACE inhibitors, two classes of antihypertensive drugs that reduce the activity of the renin-angiotensin II system, should be among the preferred first-step drugs for the treatment of hypertension.
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PMID:Drugs that interrupt the renin-angiotensin system should be among the preferred initial drugs to treat hypertension. 1267 27

The theoretical advantages of the angiotensin II receptors blockers (ARB) are slowly but progressively becoming a reality for patients with congestive heart failure. ARB are recommended in patients who cannot take ACE inhibitors as a plausible alternative for modulating the renin angiotensin system. After the recently published Val-HeFT trial, the addition of an ARB (valsartan) can be considered in patients who remain severely symptomatic despite optimal therapy in order to reduce hospitalization for heart failure and improve symptoms particularly if the patients cannot tolerates beta-blockers. Among patients with type 2 diabetes and no clinical signs of congestive heart failure ARB (losartan) are able to reduce the probability of developing congestive heart failure.
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PMID:[Angiotensin receptor antagonists and ACE inhibitors in heart failure: alternative or combined therapies?]. 1269 71

Exercise improves insulin resistance and has beneficial effects in preventing and treating type 2 diabetes. However, aerobic exercise is hindered in many type 2 diabetic patients because of advancing age, obesity, and other comorbid conditions. Weight lifting or progressive resistance training (PRT) offers a safe and effective exercise alternative for these people. PRT promotes favorable energy balance and reduced visceral fat deposition through enhanced basal metabolism and activity levels while counteracting age- and disease-related muscle wasting. PRT improves insulin sensitivity and glycemic control; increases muscle mass, strength, and endurance; and has positive effects on bone density, osteoarthritic symptoms, mobility impairment, self-efficacy, hypertension, and lipid profiles. PRT also alleviates symptoms of anxiety, depression, and insomnia in individuals with clinical depression and improves exercise tolerance in individuals with cardiac ischemic disease and congestive heart failure; all of these aspects are relevant to the care of diabetic elders. Moreover, PRT is safe and well accepted in many complex patient populations, including very frail elderly individuals and those with cardiovascular disease. The greater feasibility of using PRT over aerobic exercise in elderly obese type 2 diabetic individuals because of concomitant cardiovascular, arthritic, and other disease provides a solid rationale for investigating the global benefits of PRT in the management of diabetes.
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PMID:Battling insulin resistance in elderly obese people with type 2 diabetes: bring on the heavy weights. 1271 22

Both type 1 and type 2 diabetic patients have an increased incidence of ischemic heart disease and congestive heart failure. Cardiovascular disease accounts for up to 80% of the excess mortality in patients with type 2 diabetes. The burden of cardiovascular disease is especially pronounced in diabetic women. Factors that underlie diabetic heart disease include multiple vessel coronary artery disease, long-standing hypertension, metabolic derangements such as hyperglycemia and dyslipidemia, microvascular disease, and autonomic neuropathy. There is also increased sudden death associated with diabetes, which is due, in part, to the underlying autonomic neuropathy. This article reviews diabetic cardiac disease, with an emphasis on type 2 diabetes.
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PMID:Heart disease in diabetic patients. 1276 70

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

The renin-angiotensin system evolved to maintain volume homeostasis and blood pressure and to prevent ischemia during acute volume loss. But in the present age, these mechanisms are redundant, and the clinical significance of angiotensin II results from its pathologic effects, which are mediated by the angiotensin II type 1 (AT(1)) receptor. Activation of AT(1) receptors has been linked to pathologic processes that contribute to atherosclerosis and ischemic events, including oxidative stress, inflammatory processes, low-density lipoprotein cholesterol trafficking, and prothrombotic states. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of the angiotensin II receptor blocker (ARB) telmisartan, the angiotensin-converting enzyme (ACE) inhibitor ramipril, and combination therapy with telmisartan plus ramipril for reducing cardiovascular risk. The ARB telmisartan is distinguished by its long duration of action, which compares favorably with some other ARBs and conventional antihypertensives. Ramipril was shown in the Heart Outcomes Prevention Evaluation (HOPE) study to reduce the risk for myocardial infarction (MI) and other cardiovascular events in patients at high risk for cardiovascular events but without heart failure or a low ejection fraction. The ONTARGET program consists of 2 randomized, double-blind, multicenter international trials: a principal trial, ONTARGET, and a parallel trial, Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease (TRANSCEND). The treatment arms for the principal ONTARGET study are telmisartan 80 mg, ramipril 10 mg, and combination therapy with telmisartan 80 mg plus ramipril 10 mg; for the parallel study TRANSCEND, the treatment arms are telmisartan 80 mg and placebo. Both trials will assess cardiovascular outcomes in patients at high risk using the same criteria as that of the HOPE study, with a single exception: the TRANSCEND trial will enroll patients who do not tolerate ACE inhibitor treatment. The primary end points in both ONTARGET and TRANSCEND are death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. The secondary end points include newly diagnosed heart failure, revascularization, new-onset type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia, and newly diagnosed atrial fibrillation; these will be used for hypothesis generation.
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PMID:The ongoing telmisartan alone and in combination with ramipril global endpoint trial program. 1278 6

Over the past three decades, we have witnessed an improvement of survival in those patients with the trio of metabolic syndrome, prediabetes, and overt type 2 diabetes mellitus. Revolutionary changes in technology and an improved understanding of the mechanisms involved in acute coronary syndromes have resulted in this observation. Due to advances in coronary care, we are currently at a crossroads, wherein, the mortality from acute cardiovascular events have been declining and the mortality associated with this trio has been increasing due to congestive heart failure (CHF). This intersect between the two causes of death represent a challenge for the future, as the numbers of patients with this deadly trio are undergoing exponential growth not only in the U.S. but also abroad as more countries undergo urbanization and adopt a western-type lifestyle of over nutrition and under exercise. Thus, we live to die another day. There are multiple metabolic toxicities in this toxic trio, which predispose to an increase in reactive oxygen species and resultant redox stress within the vascular intima and myocardium. By aggressively reducing the elevated substrates producing reactive oxygen species we may be able to restore our individual, endogenous, potent, antioxidant (antiredoxidant) network. Appropriately, we need to examine the mechanisms that result in the development and transition from diastolic and systolic dysfunction to the clinical syndrome of overt CHF with its inherent increase in morbidity and mortality.
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PMID:Myocardial redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and congestive heart failure. 1288 68

Diabetic cardiomyopathy is an ill-defined entity. This study was designed to explore the possible association between left ventricular diastolic dysfunction (LVDD) and cardiac autonomic neuropathy (CAN) independently from metabolic control. Three groups of 10 age-matched men each with well-controlled type 2 diabetes were studied: (1) subjects with normal diastolic function, (2) subjects with LVDD characterized by impaired LV relaxation, and (3) subjects with a more severe form of LVDD characterized by a pseudonormalized pattern of LV filling. No subject had evidence of clinical diabetic complications, coronary artery disease (CAD), hypertension, congestive heart failure, or thyroid or overt renal disease, and all had a negative maximal exercise test. LVDD was evaluated by Doppler echocardiographic and CAN was evaluated using spectral analysis of heart rate variability (HRV; time and frequency domains) from 24-hour Holter recordings. Findings showed that the high frequency power (HF: 0.15 to 0.4 Hz) tends to decrease with worsening diastolic function; 5.0 +/- 0.2 ms(2) (mean +/- SE) in group 1, 4.2 +/- 0.3 ms(2) in group 2, and 3.9 +/- 0.4 ms(2) (P =.03) in group 3, respectively, whereas the low frequency power (LF: 0.04 to 0.15 Hz) was similar between groups. In the time domain, the mean squared differences of the successive RR intervals (rMSDD) also showed the same pattern, ie, 31.0 +/- 2.8 ms, 23.8 +/- 1.6 ms, and 21.5 +/- 2.9 ms in groups 1, 2, and 3, respectively (P =.03). The E/A ratio correlated significantly with indices of parasympathetic modulation (HF; r = 0.448, P =.013; rMSDD: r = 0.457, P =.011; pNN50: r = 0.425, P =.019). LVDD and CAN are associated in patients with otherwise uncomplicated well-controlled type 2 diabetes. The parameters defining these 2 abnormalities may serve to better define diabetic cardiomyopathy as a distinct entity and could eventually become useful prognostic indicators as it has been shown in nondiabetic populations.
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PMID:Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes. 1289 73


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