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Query: UMLS:C0011849 (diabetes)
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Inhibiting the renin-angiotensin-aldosterone system through the use of angiotensin-converting enzyme (ACE) inhibitors has proven very useful in the treatment of hypertension, congestive heart failure (CHF) and progressive renal failure. More recently, agents that directly block the angiotensin II Type 1 (AT(1)) receptor--angiotensin II receptor antagonists (AIIRAs)--have been developed. These agents are thought to have a more specific mechanism of action since they do not affect other hormone systems as do the ACE inhibitors. Whether such specificity results in a different efficacy profile is still being determined. However, these drugs are extremely well-tolerated and very safe. AIIRAs are effective in the reduction of both systolic and diastolic blood pressure and compare favourably to other classes of agents. Recent results indicate that at least one AIIRA has a favourable effect on stroke in hypertensive patients with left ventricular hypertrophy. Additional studies with other members of the class will provide further information on similar outcomes. In CHF patients, ACE inhibitors remain the drug of choice and AIIRAs are best utilised in patients who cannot tolerate an ACE inhibitor or in those receiving an ACE inhibitor who cannot tolerate a beta-blocker and need additional therapy. AIIRAs are effective in slowing the progression of renal failure in patients with Type II diabetes and may be effective in other proteinuric conditions. Whether they are more or less effective than ACE inhibitors is unknown. Overall, AIIRAs represent an important addition to the armamentarium of cardiovascular therapies with an excellent safety record and an emerging profile of utility in multiple cardiovascular conditions.
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PMID:Risk-benefit assessment of angiotensin II receptor antagonists. 1290 48

The frequency of arterial hypertension occurrence in polish population amounts to 30-40%, among diabetics is significantly higher-70%. According to the WHO/ISH Guidelines all hypertensive patients with diabetes are included into the "high risk group" independent of hypertension stage. Pharmacological treatment of hypertension is this group of patients has a particular meaning. Among hypertensive patients the degree of blood pressure lowering is more effective for cardiovascular risk reduction than choice of drug. This fact is well documented in clinical trials comparing antihypertensive efficacy of old and new antihypertensive drugs (for example UKPDS, STOP 2, INSIGHT). From the other point of view renal protection and metabolic benefits, as well as reduction of target organ damage are more advantageous for angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium antagonists than for diuretics and beta-blockers. Despite fast progress in clinical research on new antihypertensive drugs (especially AT1 receptor inhibitors) ACE-I seem to still remain still the "first choice" for hypertensive diabetics. Adequate blood pressure control among diabetic hypertensives is of special importance and usually needs appropriate combined antihypertensive therapy. Our review presents detailed information about treatment advantages and disadvantages of drugs from different antihypertensive classes in light of current clinical trials and international guidelines.
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PMID:[Antihypertensive treatment for patients with hypertension and diabetes type II--current clinical research]. 1293 58

This study evaluated the effect of losartan, an angiotensin II receptor antagonist, on cardiovascular autonomic function and large sensory nerve fiber function in individuals with diabetes mellitus. In a double-blind placebo-controlled trial, individuals were randomly assigned to treatment with a daily oral dose of 50-mg losartan (n=24) or placebo (n=20) for 12 months. Tests of cardiovascular autonomic function (i.e., RR-variation during deep breathing and the Valsalva maneuver) and of large sensory nerve fiber function (i.e., vibratory thresholds) were measured at baseline and at 12 months. No significant difference at baseline was found for duration of diabetes, glycemic control, blood pressure, or body mass index (BMI) between the two groups. After 12 months, the decline in RR-variation that occurs over time appeared to be less for those taking losartan. There was, however, no statistically significant change in the results for any of the tests of cardiovascular autonomic function or vibratory thresholds between the groups. Multivariate analyses in the losartan study group revealed an independent association of duration of diabetes, change in (reduced) systolic blood pressure (SBP), and improved vibratory thresholds. This association was particularly noted for women. Pharmacologic agents may affect cardiovascular autonomic function by favorable or detrimental changes in the electrophysiology of the heart. The results of this study indicate that, although losartan may have slowed the normal decline in RR-variation, it did not result in any significant improvement in cardiovascular autonomic nerve fiber function. An association of vibratory thresholds and SBP was observed.
J Diabetes Complications
PMID:Effect of treatment with losartan on cardiovascular autonomic and large sensory nerve fiber function in individuals with diabetes mellitus: a 1-year randomized, controlled trial. 1295 58

A 54-year-old man with diabetes mellitus, peripheral vascular disease, and hypertension was admitted to the hospital for an acute exacerbation of chronic heart failure. Therapy with intravenous furosemide and oral losartan 100 mg twice/day was begun. Ten days later, the patient's blood urea nitrogen and serum creatinine levels rose and peaked at 110 and 6.0 mg/dl, respectively. His serum potassium level increased to 5.7 mg/dl, urine output dropped to 400 ml over 24 hours, and mental status changes occurred. Magnetic resonance angiography revealed bilateral renal artery stenosis. After losartan was discontinued and hemodialysis was performed for 3 consecutive days, the patient's renal function returned to his baseline level. Reports in the medical literature reinforce the importance of recognizing that angiotensin-converting enzyme inhibitors should be used with caution in patients with bilateral renal artery stenosis. However, the literature is not as definitive about using of angiotensin II receptor blockers (ARBs) in these patients. Our patient's experience suggests that ARBs should be used with caution in patients with bilateral renal artery stenosis. Clinicians should be aware that renal failure might occur when using ARBs in these patients.
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PMID:Acute renal failure secondary to angiotensin II receptor blockade in a patient with bilateral renal artery stenosis. 1516 10

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.
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PMID:Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat. 1453 4

Our previous publication has stressed the benefits of losartan, an angiotensin II receptor blocker, on the permeability of blood-brain barrier (BBB) and blood pressure during L-NAME-induced hypertension. This study reports the impacts of anti-hypertensive treatment by losartan on the brain endothelial barrier function and the arterial blood pressure, during acute hypertension episode, in experimentally diabetic hypertensive rats. Systolic blood pressure measurements were taken with tail cuff method before and during administration of L-NAME (0.5 mg/ml). We induced diabetes by using alloxan (50 mg/kg, i.p). Losartan (3 mg/kg, i.v) was given to rats following the L-NAME treatment. Acute hypertensive vascular injury was induced by epinephrine (40 microg/kg). The BBB disruption was quantified according to the extravasation of the Evans blue (EB) dye. L-NAME induced a significant increase in arterial blood pressure on day 14 in normoglycemic and hyperglycemic rats (p < 0.05). Losartan significantly reduced the increased blood pressure in hypertensive and diabetic hypertensive rats (p < 0.01). Epinephrine-induced acute hypertension in diabetic hypertensive rats increased the content of EB dye dramatically in cerebellum and diencephalon (p < 0.01) and slightly in both cerebral cortex (p < 0.05). Losartan treatment reduced the increased BBB permeability to EB dye in the brain regions of diabetic hypertensive rats treated with epinephrine (p < 0.05). This study indicates that, in diabetic hypertensive rats, epinephrine administration leads to an increase in microvascular-EB-albumin efflux to brain, however losartan treatment significantly attenuates this protein's transport to brain tissue.
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PMID:Effect of losartan on the blood-brain barrier permeability in diabetic hypertensive rats. 1456 28

The incidence of congestive heart failure in the US population is increasing as more women and men survive with chronic hypertensive and atherosclerotic heart disease. Almost half the patients in the US with heart failure are women. Hypertension, diabetes mellitus, and cigarette smoking are all more potent risk factors for the development of heart failure in women than in men. Important differences in presentation and mortality explain gender differences in the clinical course of heart failure. Overall mortality is lower for women than for men with symptomatic heart failure. Some but not all of this difference can be explained by a lower rate of ischemic heart disease. Standard treatments for congestive heart failure, including angiotensin converting enzyme inhibitors and beta-blockers, have been shown to be equally efficacious in men and in women. Preliminary data on angiotensin II receptor blockers suggests equivalent benefit with further trial data awaited. Peripartum cardiomyopathy is a form of heart failure unique to women, occurring in the last stages of pregnancy or within 5 months after delivery. Approximately half of affected women regain normal ventricular function but for those who do not, the risk of recurrent symptomatic heart failure and mortality during subsequent pregnancies is high.
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PMID:Heart failure in women. 1458 Mar 3

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group ( P = 0.02) and 23% lower than that in the amlodipine group ( P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group ( P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group ( P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group ( P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (-11% and -38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan.
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PMID:Treatment of diabetic nephropathy with angiotensin II receptor antagonist. 1458 37

The renin-angiotensin system (RAS) plays an important role in the development of cardiovascular diseases. The favorable effects of inhibitors of this system are mainly due to a decrease of the production of angiotensin II. Usual association between angiotensin II receptor antagonists (AIIA) and angiotensin-converting enzyme (ACE) inhibitors results of a mutual action on the RAS, but important differences exist. ACE inhibitors demonstrated major benefits in heart failure and in post-infarction. In diabetic patients, ACE inhibitor treatment is associated with nephroprotective effects. In four main studies ACE inhibitors didn't demonstrated superior effect on primary outcome compare to standard antihypertensive treatment (diuretics or beta-blockers). However, in HOPE and PROGRESS studies, ACE inhibitors decrease myocardial infarction incidence, even after arterial pressure adjustment. Can we expect the same effects with the AIIA? Of course a direct comparison would be preferable, but some differences emerge. In a main study, AIIA treatment was compared to a standard antihypertensive treatment. The LIFE trial demonstrated superior benefits with losartan than with beta-blocker atenolol for the same degree of blood pressure reduction in hypertensive patients with left ventricular hypertrophy. Losartan had particularly strong effect on risk for stroke and prevented new-onset diabetes. So we have some data to emit the hypothesis that ACE inhibitors decrease the incidence of myocardial infarction and AIIA the incidence of stroke.
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PMID:[Angiotensin-converting enzyme inhibitors and/or angiotensin II receptors antagonists in the treatment of arterial hypertension]. 1474 83

Hypertension is often accompanied by type 2 diabetes mellitus. Recently, the American Diabetes Association (ADA) published guidelines on the treatment of hypertension in adult patients with diabetes mellitus. However, the views of general physicians on how to control blood pressure (BP) in diabetic patients and the impact of the ADA guidelines in Japan are still not known. We conducted an internet survey in May 2002: Questionnaires were e-mailed to a total of 3,616 medical doctors, of whom 441 (12.2%) properly responded. About half of the respondents (48.3%) had already read the ADA guidelines. Before being given an outline of the guidelines, the respondents' average BP level for starting medication was 152/94 mmHg, and the BP goal 133/83 mmHg; after reading the outline, these values were 149/92 and 132/82 mmHg, respectively. The goal BP decreased more after reading the guidelines in doctors who had not previously read the ADA guidelines than in those who had already read. After being given an outline of the ADA guidelines, 40.3% of respondents reported that they would select, as a first-line agent, an angiotensin II receptor antagonist (ARB), 35.6% an angiotensin-converting enzyme inhibitor (ACEI), and 18.6% a calcium channel blocker (CCB); as a second-line medication, 39.7% of the respondents would select a CCB. Seventy percent of doctors reported having at least one patient receiving CCB monotherapy; after reading the guidelines, 41.5% of these doctors said they would continue CCB monotherapy, 36.6% said they would add an ACEI or ARB, and 29.7% planned to change to an ACEI or ARB. In conclusion, our data suggest the impact of the ADA guidelines on the target BP and the first choice of antihypertensive medication in diabetic patients. ARBs and ACEIs became first-line medications, and CCBs became second-line medications to achieve the BP goal and prevent organ damage.
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PMID:Trends in blood pressure control in hypertensive patients with diabetes mellitus in Japan. 1462 Sep 27


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