UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Type 2 diabetes is becoming very common and is closely linked to physical inactivity and obesity. It is associated with clustering of coronary risk factors and 60-80% of cases have hypertension. The first therapeutic action is appropriate adjustment of life style. Anti-hypertensive therapies such as diuretics, ACE inhibitors and calcium antagonists have been effective in reducing cardiovascular events in type 2 diabetes, though calcium antagonists may be less effective than older therapies and ACE-inhibitors in reducing the risk of heart attacks and heart failure (but possibly more effective in stroke reduction). Beta-blockers (BBs) have a poor image as a potential therapy due to apparent adverse effects on surrogate end-points such as insulin-resistance. However large, controlled trials have shown BBs to be highly effective in reducing the risk of cardiovascular events and death in post myocardial infarction patients with diabetes. The UKPDS study in type 2 diabetics with hypertension showed first-line beta-blockade to be at least as effective as ACE-inhibition in preventing all primary macrovascular and microvascular end-points. The active ingredient appears to be beta-1 blockade, acting not only to lower blood pressure but also to prevent sudden death and cardiovascular damage stemming from chronic beta-1 stimulation associated with raised noradrenaline activity. By contrast, in the LIFE study atenolol was less effective than the angiotensin receptor antagonist losartan in reducing cardiovascular events and all-cause mortality in mainly elderly hypertensives with diabetes. Thus the best beta-blocker results in reducing hard cardiovascular end-points occur in hypertension studies (including the UKPDS study) involving younger/middle aged (say less than 60-65 years) patients, with relatively high sympathetic activity, relatively compliant/elastic arteries (narrow pulse-pressure) and normally functioning beta-1 receptors. In elderly hypertensive patients beta-blockers may be given as second-line therapy on the back of a low-dose diuretic (but possibly as first line agent in elderly hypertensives with prior myocardial infarction). Thus inappropriate attention to surrogate end-points can lead to faulty prescribing habits. Beta-blockers, currently severely underprescribed, should be considered as a first line therapeutic option for all diabetics with ischaemic heart disease or younger/middle aged diabetics with hypertension (but co-prescribed with low dose diuretic therapy in the elderly). The active ingredient for cardiovascular protection appears to be beta-1 blockade; optimal efficacy in lowering blood pressure and safety e.g. reducing risk of bronchoconstriction, is achieved by choosing an agent with high beta-1 selectivity.
...
PMID:Beta-blockers and diabetes: the bad guys come good. 1265 16

For patients with diabetes mellitus (DM), chronic complications can be devastating. Cardiovascular illness, the major cause of morbidity and mortality among these patients, encompasses macrovascular disease, with heart attacks, strokes, and gangrene; and microvascular disease, with retinopathy, nephropathy, and neuropathy (somatic and autonomic). Macrovascular events occur earlier in individuals with DM than in people without DM, and the underlying pathologies are often more diffuse and severe. Diabetic arteriopathy, which encompasses endothelial dysfunction, inflammation, hypercoagulability, changes in blood flow, and platelet abnormalities, contributes to the early evolution of these events. Efforts are under way to determine interventions that may have the potential to prevent or halt the complications of DM. Tight glucose and blood pressure (BP) control is known to improve the vascular status of patients with DM by varying degrees. Use of anti-inflammatory drugs and lowering low-density lipoprotein cholesterol (LDL-C) levels are also useful. An emerging understanding of the importance of small, dense LDL-C and the anti-inflammatory effects of statins has provided new algorithms for primary prevention of macrovascular disease. Antiplatelet agents have also been shown to be effective in the secondary prevention of cardiovascular events. In the ideal world every risk factor would be addressed and each person with DM would have excellent glycemic control, low to normal BP, and a low LDL level, and would be taking an angiotensin-converting enzyme (ACE) inhibitor, together with a statin, aspirin, and clopidogrel. Under these near-perfect conditions, the emerging epidemic of macrovascular disease could be contained. Microvascular disease, however, is a consequence of hyperglycemia. For every 1% reduction in glycosylated hemoglobin it is possible to achieve a 22% to 35% reduction in the microvascular complications. BP control is vital and the liberal use of ACE inhibitors and angiotensin receptor blockers to slow the progression of renal disease should drastically reduce the incidence of blindness, dialysis, and amputations. This article provides an overview of prevention of macrovascular disease such as stroke, myocardial infarction, and peripheral arterial disease and microvascular complications such as retinopathy, nephropathy, and neuropathy in patients with DM.
...
PMID:Prevention of the complications of diabetes. 1265 55

Aggressive therapy for patients with type 2 diabetes mellitus and renal disease is warranted given the natural history of this disease. Although antagonizing the renin-angiotensin system is clearly important, how this is accomplished is of considerable controversy. On the one hand, recent clinical trials of patients with type 2 diabetes mellitus with renal disease demonstrate unequivocally the renal protective effect of angiotensin receptor blockers (ARBs). Although the results of the recently published LIFE trial are encouraging, inconsistencies have been observed with ARBs in reducing cardiovascular end points. On the other hand, angiotensin-converting enzyme inhibitors have a dramatic effect in reducing cardiovascular events but have not been shown convincingly to reduce progression of renal disease in patients with type 2 diabetes mellitus. These studies leave us in a quandary as to the optimal initial treatment regimen for patients with type 2 diabetes mellitus and renal disease despite the recent recommendations from the American Diabetes Association (Alexandria, Va). Given the fact that many of these individuals will require administration of multiple antihypertensive agents, perhaps the initial treatment with a combination of an ARB and angiotensin-converting enzyme inhibitor affords optimal cardiovascular and renal protection for patients with type 2 diabetes mellitus and renal disease. Future clinical trials should be designed to address this issue.
...
PMID:Combination therapy with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists in the treatment of patients with type 2 diabetes mellitus. 1274 99

The purpose of this study was to assess the management of both hypertension and micro/macroalbuminuria in a cohort of type II diabetic patients. In the first 6 months of the year 2000, 5815 diabetic patients were identified through prescriptions for antidiabetic drugs in our sanitary district (191 568 inhabitants). In all, 65% (3810) of these type II diabetic patients were also given prescriptions for antihypertensive drugs. A total of 400 diabetic patients were randomly selected and 171 entered the study (gender: 94/77 M/F; age: 66.6+/-8 years; diabetes duration: 12+/-9 years): 100 patients (group DT) were treated with antihypertensive drugs and 71 (group DU) were untreated. Blood pressure, urine albumin-to-creatinine ratio (ACR), and glycated haemoglobin were measured in the two groups. A total of 80% (57/71) of DU patients were hypertensive (BP>/=130/85 mmHg). Specifically, 24.4% had diastolic hypertension (BP>/=85 mmHg) and 79% systolic hypertension (BP>/=130 mmHg). Only 63% (100/157) of the hypertensive patients were treated with antihypertensive drugs (two drugs/patient on average, range 1-5). In addition, only 13% of the DT patients were adequately controlled (BP<130/85 mmHg), while the others had above target blood pressure levels (14%: 130-139/85-89 mmHg; 40%: 140-159/90-95 mmHg, and 33%>/=160/95 mmHg). Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) were included in the antihypertensive medical regimen in 70% of the DT patients (ACE-I: 62%; ARB: 8%; diuretics: 39%; dihydropyridine calcium antagonists: 38%; alpha-blockers: 20%, beta-blockers: 17%; clonidin: 8%; nondihydropyridine calcium antagonists: 5%). Only 33% of type II diabetic patients underwent a screening for microalbuminuria as assessed on clinical records. The same percentage of micro- and macroalbuminuric patients (13.5%) was observed in the DT group, whereas 25% micro vs 3% macro were found in the DU group. In all, 73% of microalbuminuric patients were not on ACE-I/ARB. Hypertensive type II diabetic patients were often left untreated and only a minority of those treated were optimally controlled. The importance of an elevated systolic pressure is underestimated and the number of antihypertensive drugs prescribed insufficient. Screening and treatment of albuminuria are inadequate.
...
PMID:How well are hypertension and albuminuria treated in type II diabetic patients? 1276 4

Guidelines for medical treatment are becoming increasingly popular and many guidelines have been produced by various societies in diabetes, hypertension, and renal disease as well as general medicine. By their nature, they are outdated considering the rapid and efficient publication of many papers related to the treatment of hypertension in diabetes. Increased blood glucose causes vascular damage and abnormal vascular structure all over the body, an abnormal structure that is especially vulnerable to high blood pressure, even within the so-called normal range. There is now more and more evidence, especially in diabetics, that blood pressure should be as low as possible. In this context, it is important to stress that the so-called J-shaped relationship between blood pressure and mortality may not be so relevant. Major epidemiological studies came from the Framingham and the Multiple Risk Factor Intervention Trial (MRFIT) Diabetic Cohort. The MRFIT Cohort showed that cardiovascular mortality was increased by a factor of 2-4 in diabetic patients, and there was a clear association between systolic blood pressure and complications without any threshold value. It could be suggested that since diabetes is an important cardiovascular risk factor, a lower value (130/85 mmHg) than for non-diabetics (140/90 mmHg) should be proposed. The tight blood pressure control arm of the United Kingdom Prospective Diabetes Study was <150/85 mmHg (achieved 144/82 mmHg) and the aim in the less tight control arm was <180/105 mmHg (achieved 154/87 mmHg). In the tight control group, 29% needed three or more antihypertensive drugs. In the Hypertension Optimal Treatment study, the frequency of major cardiovascular disease events in the group with target <80 mmHg (achieved 144/81 mmHg) was 11.9/1000 patients/year, which was significantly lower than the event rate (24.4/1000 patients/year) in the group with target <90 mmHg (achieved 148/85 mmHg). A reduction in the frequency of diabetic nephropathy by angiotensin-converting enzyme (ACE) inhibitor treatment in normotensive lean microalbuminuric type 2 diabetic patients has been shown. However, it is impossible from the present data to draw any conclusions with respect to effect on the main composite endpoint of ACE inhibition in microalbuminuric type 2 diabetic patients without previous cardiovascular events or without hypertension. Recent published studies have also demonstrated beneficial effects with angiotensin receptor blockers (ARBs) in hypertensive patients with type 2 diabetes and nephropathy. Diuretics form a very important basis for antihypertensive treatment, also often in combination with agents that inhibit the renin-angiotensin system. Several studies show that treatment with the diuretic indapamide reduces the level of microalbuminuria in patients with type 2 diabetes. Diuretics were used as an adjunctive to reduce blood pressure in all studies; it is therefore understandable that many guidelines suggest that diuretics form part of the treatment of hypertension in diabetics. Many studies of an epidemiological nature and follow-up studies in diabetic patients show that blood pressure control is of vital concern in the prevention of diabetic complications, and indeed the usual criteria for good blood pressure control may not be stringent enough in diabetic patients. Many classes of antihypertensives may be used, but it appears that diuretics, such as indapamide sustained release (SR), constitute an important proposal in all treatment strategies.
...
PMID:New treatment guidelines for a patient with diabetes and hypertension. 1276 64

Several studies indicate that treatment of hypertension in the United States does not follow recommendations from expert bodies. We thus implemented a program using academic detailers to increase practitioner compliance with antihypertensive treatment guidelines. Five Veterans Affairs medical facilities including academic medical centers and community based outpatient clinics were chosen for the intervention. Pharmacists were trained as academic detailers, and the intervention included lectures, educational materials, provider profiling, and meetings with 25 to 50 providers each. After intervention, the proportion of hypertensives receiving calcium antagonists decreased from 43% to 38% (P <.001), whereas the proportion receiving a beta blocker or thiazide diuretic increased from 58% to 64% (P <.001). For hypertensive subjects with diabetes mellitus or congestive heart failure, the proportion receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker increased from 72% to 76% for the former and from 74% to 78% for the latter (P <.001 for both). Among hypertensive subjects with coronary artery disease an increase in beta blocker use was noted after intervention (P <.001 for change from baseline). Prescribing patterns after academic detailing more closely followed national recommendations.
...
PMID:Academic detailing to improve antihypertensive prescribing patterns. 1279 3

As the epidemic of diabetes spreads so does the number of patients at risk for developing diabetic nephropathy, which occurs in 20% to 40% of all diabetic patients. Indeed, diabetes is the most common cause of end-stage renal disease (ESRD) in the United States, accounting for > 40% of patients starting renal replacement therapy each year. Unfortunately, the outcome for diabetic patients with ESRD is worse than that for nondiabetic patients because of comorbid conditions in the diabetic population. However, with early and intensive blood glucose and blood pressure control--including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--the development and progression of diabetic kidney disease can be slowed.
...
PMID:Diabetic nephropathy. 1280 Apr 76

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.
...
PMID:Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. 1281 10

Prevention of the major causes of ESRD, hypertension, and diabetes, is possible. Careful glycemic control can prevent diabetes nephropathy. BP control can likely prevent the large majority of hypertensive renal disease. Testing for diabetic renal disease is well founded. In contrast, screening for hypertensive kidney disease is less well defined. Most established renal disease can be treated with glycemic control in the case of diabetes, BP treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and dietary protein restriction. Other therapeutic targets have been proposed, but are not well established. Future research should focus on defining the high risk patients, developing better markers of risk, and designing additional therapies.
...
PMID:Prevention of the development and progression of renal disease. 1281 20

To determine the effect of a low-dose angiotensin receptor blocker, candesartan, on early kidney damage associated with diabetes. Fifty-two patients with type 2 diabetes with normo- and microalbuminuria participated in this study. Nineteen patients with high-normal and mildly high blood pressure received low-dose candesartan cilexetil at 4 mg daily (candesartan group), and 33 patients did not receive candesartan (control group). Blood pressure, urinary excretion of albumin, transferrin, and type IV collagen (expressed as urinary creatinine index) and plasma parameters were determined at baseline and at 2, 6, 12 and 18 months after the start of candesartan therapy. Baseline urinary albumin, transferrin, and type IV collagen excretions was similar in the control and candesartan groups. The higher baseline systolic blood pressure was decreased by candesartan treatment to a level similar to that in the control group, such that blood pressure was comparable between the control and candesartan groups during the run-in period. In the control group, urinary albumin excretion was significantly increased at 18 months when compared with baseline, while urinary albumin excretion did not increase in the candesartan group throughout the study. Urinary transferrin excretion was significantly increased at 6, 12, and 18 months when compared with baseline in the control group, while it did not increase in the candesartan group during the study. In both groups, urinary type IV collagen excretion did not change significantly during the study. Hemoglobin A1c, serum urea nitrogen, creatinine, albumin, and lipids were comparable between the two groups throughout the study. In conclusion, low-dose candesartan can prevent early kidney damage in type 2 diabetic patients with mildly higher blood pressure independently of its hypotensive action.
...
PMID:Low-dose candesartan cilexetil prevents early kidney damage in type 2 diabetic patients with mildly elevated blood pressure. 1286 1

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>