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

Evidence now exists suggesting a pathologic role for angiotensin II in patients with cardiovascular disease and those with risk factors. Clinical trials such as the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE), the Heart Outcomes Prevention Evaluation Study (HOPE), the African American Study of Kidney Disease and Hypertension (AASK), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study have clearly demonstrated that blood pressure reduction is important in hypertension and diabetes. If this can be accomplished with agents that block the renin-angiotensin system, then additional clinical benefit will be achieved. Clinical data on angiotensin-converting enzyme inhibitors (ACEIs) are well established, while emerging data on the use of angiotensin II receptor blockers (ARBs) continue to grow. There is evidence supporting the concept of angiotensin II escape in the presence of ACEIs. The question that remains to be answered is whether a combination of both agents (ACEIs and ARBs) can improve clinical outcomes. Ongoing clinical trials will answer this question.
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PMID:Angiotensin II blockade: a therapeutic strategy with wide applications. 1464 Apr 63

The incidence of diabetes as cause of end-stage renal failure (ESRF) has significantly increased, and will continue to grow during the next few years. Moreover, diabetic nephropathy is associated with elevated cardiovascular morbidity and mortality. These guidelines focus on the possible intervention strategies to prevent and treat ESRF in diabetic patients. In normoalbuminuric patients, glycated haemoglobin levels less than and equal to 7.5% is mandatory for reducing the risk of incipient nephropathy. Furthermore, blood pressure levels < 130/80 mmHg are strongly recommended. In microalbuminuric patients, glycated hemoglobin levels below 7.5% and blood pressure levels below 130/80 mmHg (120/70-75 mmHg in patients < 50 years) are recommended. Moreover, there is evidence that inhibition of the rennin-angiotensin-aldosterone system, either by angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin II receptor antagonists (AIIRA) is able to reduce the incidence of overt nephropathy, regardless of blood pressure levels. Current guidelines recommed ACE-I as the first-choice drug in type 1 diabetes, while both ACE-I and AAIRA are considered first-choice therapy in type 2 diabetes. In proteinuric patients it is uncertain whether glycemic control affects the progression of nephropathy, which in turn is dramatically influenced by blood pressure. Optimal blood pressure levels are below 130/80 mmHg (120/70-75 mmHg in patients < 50 years). In type 1 diabetes there is consensus on the renoprotective role of ACE-1. In type 2 diabetes, two recent trials demonstrated that AIIRA are more effective than conventional therapy or calcium channel blockers in slowing down the progression of nephropathy. ACE-I are indeed recommended as first-choice drugs in type 1 diabetes while AIIRA are the first-choice agents for ESRF prevention in type 2 diabetes. Dialysis treatment should be started as soon as the creatinine clearance is reduced to about 10-15 mL/min. The choice of dialysis schedule should be individualized according to clinical and adequacy criteria (CAPD weekly Kt/V > or = 2 and single HD session Kt/V > or = 1.5). Simultaneous pancreas-kidney transplantation should be the first-choice therapeutic option in type 1 diabetes, while renal transplantation has been demonstrated to significantly improve the prognosis of type 2 diabetes patients with ESRF.
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PMID:[Guidelines for diagnosis and therapy of diabetic nephropathy]. 1466 6

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists).
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PMID:Advanced glycation end products in clinical nephrology. 1467 11

Hypertension, impaired renal function, and proteinuria are commonly associated to the presence of diabetes. They play a major role in the development of cardiovascular and renal damage. Effective antihypertensive treatment reduces the progression of diabetic nephropathy and improves cardiovascular prognosis. Accordingly, tight BP control (<130/80 mmHg) is currently recommended in diabetic patients. Achieving BP targets represents the most important determinant of cardiovascular and renal protection. However, it has been suggested that specific classes of antihypertensive drugs may exert additional organ protection beyond their BP control. The pharmacologic blockade of the renin-angiotensin-aldosterone system has been shown to convey greater renal and cardiovascular protection compared with other classes of drugs. In particular, studies focusing on renal end point suggest that angiotensin-converting enzyme inhibitors (ACEI) are the first-choice drugs in type 1 diabetes. Both ACEI and angiotensin II receptor blockers prevent the progression from microalbuminuria to clinical proteinuria in type 2 diabetes, but angiotensin blockers provide better renoprotection in patients with overt nephropathy. Regarding cardiovascular protection, several studies (but not all) have shown that ACEI exert a protective effect on diabetic patients. Recently, interesting results in favor of angiotensin receptor blockers have been reported in the IDNT, RENAAL, and LIFE studies. It should be noted that to achieve maximal renal and cardiovascular protection, most diabetic patients require integrated therapeutic intervention, including not only several antihypertensive drugs, but statins and antiplatelet therapy as well.
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PMID:Optimizing therapy in the diabetic patient with renal disease: antihypertensive treatment. 1468 64

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 prevalence of chronic kidney disease (CKD) is on the rise in all ethnic groups. This is because of the increased prevalence of obesity, diabetes mellitus, the metabolic syndrome, and the inadequate control of elevated blood pressure and other cardiovascular-renal risk factors, especially in ethnic minority populations. The implications of the aforementioned trends in risk factor prevalence and control are profound. Moreover, these trends negatively impact patient quality of life and place an enormous financial burden on the health care system for the provision of care to patients with CKD, end-stage renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost importance to devise strategies that prevent kidney disease and delay progressive loss of kidney function in persons with CKD. Proven strategies include pharmacological interventions that lower blood pressure to less than target levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and reducing urinary protein excretion. It is also possible, although yet unproven, that correction of anemia and aggressive treatment of dyslipidemia may forestall the loss of kidney function. In general, ethnic minorities are underrepresented in most large trials. Recently, a few outcome clinical trials in blacks have reinforced the lessons of kidney function preservation already learned in nonblack populations. That is, the reversible risk factors for CKD appear to be virtually identical and, at least in nondiabetic CKD, pharmacological targeting of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers preserves kidney function better than non-RAAS blood pressure-lowering regimens, especially when significant proteinuria exists. Although more CKD studies in ethnic minorities are needed, until they become available, the best available evidence from the existing clinical trial database should be applied to minorities with CKD-even when specific data are not available for a specific racial or ethnic group. Why this approach? First, there are no known unique risk factors for kidney disease in any ethnic group. Second, poor control of reversible risk factors for CKD is universal, particularly in blacks and other ethnic minorities. Thus, it is logical to predict that more efficient use of strategies proven to forestall loss of kidney function will reduce the excess of CKD and ESRD in ethnic minorities relative to non-minority populations. However, medical-based strategies alone are probably not enough. The global epidemic of obesity will fuel the growing population of persons, especially among ethnic minorities, with diabetes, the main cause of CKD, ESRD, and CVD. The obesity and diabetes epidemics are unlikely to abate without innovative and ultimately effective public health approaches.
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PMID:Pharmacological strategies for kidney function preservation: are there differences by ethnicity? 1473 May 36

The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator-activated receptor-gamma (PPARgamma) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARgamma have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Here we report that telmisartan, a structurally unique angiotensin II receptor antagonist used for the treatment of hypertension, can function as a partial agonist of PPARgamma; influence the expression of PPARgamma target genes involved in carbohydrate and lipid metabolism; and reduce glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet. None of the other commercially available angiotensin II receptor antagonists appeared to activate PPARgamma when tested at concentrations typically achieved in plasma with conventional oral dosing. In contrast to ordinary antihypertensive and antidiabetic agents, molecules that can simultaneously block the angiotensin II receptor and activate PPARgamma have the potential to treat both hemodynamic and biochemical features of the metabolic syndrome and could provide unique opportunities for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.
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PMID:Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. 1500 34

Cardiovascular disease (CVD) is the major cause of mortality in dialysis patients. Aspirin, beta-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors reduce CVD mortality in the general population, as may angiotensin II receptor antagonists. The prevalence of cardiovascular risk factors and usage rates of cardioprotective agents in end-stage renal failure are unknown. A retrospective, cross-sectional study of dialysis patients was performed to compare: (i) prevalence of cardiovascular risk factors (age, hypertension, hyperlipidaemia, diabetes mellitus, and smoking); (ii) use of cardioprotective agents; and (iii) prevalence of cardiovascular disease between the time-points: 1996 (n = 262) versus 2001 (n = 369). We found an increase in the risk factors of age (53.6 +/- 14.9 years in 1996 vs 58.4 +/- 14.3 in 2001; P < 0.001) and hyperlipidaemia (45 vs 51.8%; P < 0.001) between the two time-points, with a reduction in the prevalence of smoking (14.5 vs 8.1%; P = 0.016). There was no difference in the prevalence of cardiovascular disease (37.4 vs 40.7%; P = 0.44). Cardioprotective agents were underutilized, with improvement in prescribing practice between 1996 and in 2001, especially in the usage of statins (21.4 vs 38.7% in 2001; P = 0.019). In conclusion, CVD is the primary cause of mortality in our dialysis patients. Although traditional cardiovascular risk factors affect the majority of the dialysis population, underutilization of cardioprotective agents is common. Proof of efficacy of these agents in this population of enormous risk is urgently required.
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PMID:Cardiovascular risk in dialysis patients: a comparison of risk factors and cardioprotective therapy between 1996 and 2001. 1501 18

Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects--hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.
Pediatr Diabetes 2002 Jun
PMID:Treatment of hypertension and microalbuminuria in children and adolescents with type 1 diabetes mellitus. 1501 66

Type 2 diabetes is increasing globally and is a major cause of conditions such as cardiovascular disease, retinopathy and nephropathy. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study demonstrated that the progression of renal disease could be slowed by tight glycaemic control and treating any associated hypertension with angiotensin-converting enzyme inhibition. Recent clinical trials have supported the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, resulting in the approval of new therapeutic indications in the United States and Europe. The objective of this review is to demonstrate how results from the Program for Irbesartan Mortality and morbidity Evaluation studies apply to clinical practice, and to show how the benefits of irbesartan therapy can be realised at any stage of renal disease in patients with diabetes.
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PMID:What is the impact of PRIME on real-life diabetic nephropathy? 1511 95


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