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)

Evidence suggests that ACE inhibitors can be advantageous for prevention and halting progression of both micro- and macrovascular complications in patients with diabetes mellitus. ACE inhibitors are useful antihypertensive agents in both type 1 and type 2 diabetes; however, ACE inhibitor therapy often needs to be supplemented with calcium channel antagonists, beta-blockers or diuretics to achieve good blood pressure control. ACE inhibitors are also indicated in non-hypertensive patients with type 1 and type 2 diabetes who have micro- or macroalbuminuria. The effect of ACE inhibitors in halting the development and progression of retinopathy and, potentially, neuropathy needs further proof in large-scale studies. More recently, angiotensin II receptor antagonists are emerging as drugs with the potential to be successfully included in the management of diabetic complications, especially when ACE inhibitors are not suitable because of adverse effects.
 ...
PMID:The role of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists in the management of diabetic complications. 1226 46

Diabetes mellitus is a strong risk factor for the development of cardiovascular disease, and is associated with a worse prognosis. The incidence of congestive heart failure is higher in diabetic patients, although the reasons for this increased rate are debated (higher incidence and severity of coronary heart disease and arterial hypertension, or a true diabetic cardiomyopathy). The treatment of heart failure in diabetic patients does not differ from that of non-diabetic patients, although recent studies of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers offer interesting new perspectives.
 ...
PMID:[Prevention and treatment of congestive heart failure in diabetic patients]. 1238 94

Diabetes mellitus is the most common cause of end-stage renal disease in the United States, accounting for about 50% of all new cases. Although we previously established the renoprotective benefits of angiotensin converting enzyme (ACE) inhibitors in patients with coexisting hypertension and type 1 diabetes, evidence of the renoprotective effect of ACE inhibitors in patients with type 2 diabetes is less clear. We conducted the Irbesartan Diabetic Nephropathy Trial (IDNT) to determine whether the angiotensin II receptor blocker (ARB) irbesartan slows the progression of nephropathy in patients with type 2 diabetes independently of its blood pressure (BP)-lowering effect. In this randomized, controlled trial, we found that irbesartan was associated with a 20% reduction in the risk for the primary composite end point (doubling of the baseline serum creatinine concentration, development of end-stage renal disease, or death from any cause) compared with placebo (P =.02) and a 23% reduction compared with amlodipine therapy (P =.006). These results were not explained by differences in the BP that was achieved. In a separate study, losartan was shown to reduce the risk for progression of renal disease in patients with type 2 diabetic nephropathy. Angiotensin II receptor blocker therapy has also been demonstrated to slow the progression to overt nephropathy when initiated early in the course of type 2 diabetic renal disease (ie, in patients with microalbuminuria). Based on these studies, ARBs are clearly effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of their BP-lowering effect. Preclinical studies with the newest ARB, olmesartan medoxomil, suggest that this agent may provide renoprotective benefits as well.
 ...
PMID:The role of angiotensin II receptor blockers in preventing the progression of renal disease in patients with type 2 diabetes. 1238 93

The results of the EUCLID highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. We aimed to evaluate the effectiveness of candesartan cilexetil(TCV-116), a potent angiotensin II receptor antagonist, in ameliorating retinal disorders in stroke-prone spontaneously hypertensive rats(SHRSP) with storeptozotocin(STZ)-induced diabetes. Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated SHRSP compared with a non-treated SHRSP group matched for age. Treatment with TCV-116(3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potentials, but had no effect on plasma glucose concentrations. These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages.
 ...
PMID:[Ameliorative effects on retinal disorder in diabetic SHRSP (stroke-prone spontaneously hypertensive rat)]. 1239 94

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I.
 ...
PMID:Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers. 1246 18

Aging is accompanied by a progressive and irreversible non-enzymatic modification of protein by carbohydrates, eventually yielding the advanced glycation end products (AGEs). Age generation (Maillard reaction) is markedly augmented in diabetes with sustained hyperglycemia but also in normoglycemic uremia and atherosclerosis. Recent studies have brought new insights into broad derangements in non-enzymatic biochemistry involving not only carbohydrates but also lipids, present in diabetes, uremia, and atherosclerosis. The latter have in common increased levels of reactive carbonyl compounds (RCOs) with attendant protein modifications ("carbonyl stress"). Carbonyl stress might be derived from 1) hyperglycemia (lipemia), 2) oxidative stress, and/or 3) impaired detoxification of RCOs. Manipulation of carbonyl stress in diabetes, uremia and atherosclerosis opens new therapeutic approaches including redox modulation, RCO detoxification, and carbonyl stress inhibition. The first generation of carbonyl stress inhibitors such as aminoguanidine trap RCOs with its hydrazine group. Unfortunately, aminoguanidine (AG) traps pyridoxal as well as noxious RCOs, so that its long-term administration in animals results in vitamin B6 deficiency and neurotoxicity. Fortunately, newer compounds devoid of such side effects, have opened exciting prospects. Widely used hypotensive agents, such as angiotensin converting enzyme (ACE) inhibitor and angiotensin II receptor antagonist, but not calcium blockers, prove more effective than AG in attenuating the production of AGEs. Unlike AG, they do not act as RCO trapping agents, but impact upon the production of RCO precursors by scavenging a variety of radicals and altering oxidative stress, a mechanism similar to that involved in the inhibitory action of nitric oxide on AGE formation. These results provide a new framework to assess families of compounds according to their mechanisms of action.
 ...
PMID:Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis ("carbonyl stress"). 1250 15

The renin-angiotensin system plays a key role in the progression of kidney disease, in addition to its well-described role in the maintenance of extracellular fluid volume and blood pressure. Recent studies have shown that blockade of the renin-angiotensin system at the level of the angiotensin II type 1 receptor can have important effects on proteinuria and the rate of progression of kidney disease in patients with type 2 diabetes mellitus. This review first discusses recent experimental studies relating angiotensin II to kidney function in diabetes mellitus and changes in glomerular permselectivity, and then focuses on recent clinical trials with angiotensin II receptor blockers in patients with type 2 diabetes mellitus.
 ...
PMID:Angiotensin II and the glomerulus: focus on diabetic kidney disease. 1264 18

Diabetic nephropathy is the leading cause of end-stage kidney disease in the United States. The majority of these cases are attributed to those with type 2 diabetes. Elevated blood pressure, proteinuria, and increased activity of the renin-angiotensin-aldosterone system (RAAS) play a major role in the development and progression of chronic kidney disease attributed to diabetes mellitus. Moreover, drugs that inhibit angiotensin II synthesis or block the angiotensin II type I receptor lower blood pressure, reduce proteinuria, and improve outcomes in patients with chronic kidney disease caused by diabetes. This article highlights improvements in the current management of diabetic nephropathy afforded by agents that inhibit the RAAS, discusses their limitations, and considers novel strategies to prevent onset and progression of diabetic nephropathy. Current opinions concerning combination drug therapy with agents that block the RAAS at multiple sites, as well as combining calcium channel blockers with either angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, are also discussed.
 ...
PMID:Appropriate drug therapy for improving outcomes in diabetic nephropathy. 1264 62

Cardiovascular disease is responsible for 70% of the deaths in diabetes mellitus. Endothelial dysfunction occurs early in atherosclerosis and can now be assessed accurately and reproducibly by noninvasive means. Hyperglycemia, insulin resistance, microvascular complications, and coexistent conditions have been shown to impair endothelial function in diabetes. Resistance to insulin's vasodilatory effect and increased free radical generation are probable mechanisms responsible for the endothelial dysfunction in this state. Improvement in glycemic control, insulin and insulin sensitizers, cholesterol lowering, hypolipidemic agents, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have improved clinical cardiovascular outcomes and have also been shown to improve endothelial function. Strategies designed to assess and improve endothelial function may be further beneficial in terms of cardiovascular outcomes in diabetes mellitus, and need to be tested in a clinical setting.
 ...
PMID:Vascular reactivity in diabetes mellitus. 1264 89

Diabetic nephropathy is the leading cause of end-stage renal disease in western or westernised countries and the largest contributor to the total cost of diabetes care around the world. In addition to the development of diabetic nephropathy and end-stage renal failure, diabetic patients with evidence of albuminuria have a much higher risk of developing myocardial infarctions, cerebrovascular accidents, severe progressive retinopathy, and peripheral and autonomic neuropathy. A cumulative incidence of diabetic nephropathy has been documented after duration of diabetes of at least 25 years in both type 1 and type 2 diabetic patients, although more recent studies have demonstrated a substantial reduction of its incidence. Before the onset of overt proteinuria, there are several renal functional changes, including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetic nephropathy. It has been postulated that diabetic nephropathy occurs as a result of the interplay of metabolic and haemodynamic factors in the renal microcirculation. Hyperglycaemia plays a pivotal role in the pathogenesis of diabetic renal disease, but genetic factors are also of crucial importance. The accumulation of advanced glycosilation end products (AGEPs), the activation of isoforms of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycaemia damages vessels. Growth factors (i.e. TGF-b, IGF-1, VEGF) may also play an important role in the pathogenesis. There is a familial clustering of diabetic kidney disease: a number of gene loci have been investigated to try to explain the genetic susceptibility to this complication. The two main treatment strategies for prevention of diabetic nephropathy are improved glycaemic control and blood pressure lowering, particularly using drugs such angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. Many potential treatment modalities in preventing and treating diabetic nephropathy are presently being evaluated; some of them will possibly be available in the near future in order to try to modify the natural course of kidney involvement and disease in patients with diabetes.
 ...
PMID:Kidney involvement and disease in patients with diabetes. 1268 18


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