Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACE-inhibitors and AT, receptor antagonists play an important role in the treatment of cardiovascular and renal diseases. The criteria of evidence-based medicine indicate that ACE-inhibitors (in appropriate combinations with other cardiovascular agents) continue to represent the treatment of first choice in chronic heart failure, post-myocardial infarction with compromised ventricular function, high cardiovascular risk, and diabetic (type 1) nephropathy. It is here that the AT1 antagonists should be used--in particular when ACE-inhibitors are not tolerated. The AT1 antagonists, Irbesartan and Losartan, are applied, at appropriately high doses, primarily in hypertensives with diabetic (type 2) nephropathy. With the current exception of chronic heart failure, no confirmed data are yet available on the value of combination treatment. The LIFE study has shown that an AT1 antagonist is superior to an established beta blocker in hypertensives with an increased risk (left-ventricular hypertrophy), in particular when diabetes mellitus is impending or already present.
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PMID:[ACE inhibitor or AT1 antagonist. Is there a differential therapy?]. 1213 23

The Losartan Intervention for Endpoint Reduction trial is one of several end-point trials that are now available with angiotensin-receptor blockers. This trial compared two regimens-losartan-based therapy to atenolol-based therapy-in 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy. In the instance of each of these therapeutic groups, hydrochlorothiazide add-on therapy was permitted as per protocol. Although blood pressures were comparably reduced in both the losartan and the atenolol-based treatment groups, stroke rate was notably less in the losartan-treatment group. The 1195 patient diabetic cohort in this trial also experienced a substantial reduction in total and cardiovascular mortality favoring losartan. An additional finding in this trial was that new-onset diabetes developed 25% less frequently in the losartan-treated group. The results of this trial are both interesting and relevant to what is an expanding use of angiotensin-receptor blockers in the hypertensive population.
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PMID:The Losartan Intervention for Endpoint Reduction (LIFE) trial-have angiotensin-receptor blockers come of age? 1214 37

During the past few years, several major intervention trials have been conducted in an attempt to determine the efficacy of specific antihypertensive agents in retarding progression of diabetic nephropathy. These studies have clearly demonstrated the importance of renin-angiotensin system blockade in attenuating progressive renal disease. The preferred initial therapy is an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin type I (AT1) receptor antagonist based on the recent 'landmark' proof-of-concept trials--the Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL). However, these clinical trials also demonstrate that aggressive blood pressure targets are needed in patients with diabetes and hypertension. This frequently requires multiple-drug therapy with several different classes of antihypertensive agents. Data from several clinical trials, including RENAAL, suggest that calcium antagonists may be added to ACE inhibitor or AT1 receptor antagonist therapy as needed to achieve target blood pressure. Calcium antagonists could, therefore, constitute an important component of the antihypertensive regimen in the management of patients with diabetic nephropathy.
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PMID:Evolving therapeutic strategies for retarding progression of diabetic nephropathy--an update for 2002. 1222 27

To date, blood-pressure lowering has been the main therapeutic objective in patients with arterial hypertension, regardless of the drug used, except for drugs selected for accompanying conditions. The LIFE study, carried out in 9,193 high-risk hypertensive patients (with ECG criteria of left ventricular hypertrophy), has shown that a therapeutic regimen based on losartan combined with a thiazide was accompanied by a significant reduction in the risk of cardiovascular complications in more than 90% of patients compared with atenolol and a thiazide over a mean follow-up period of 4.8 years. The incidence of the primary endpoints (cardiovascular death, stroke, and myocardial infarction) was 11% in the losartan group and 13% in the atenolol group (13% relative risk reduction, p = 0.021). Losartan therapy was associated with more benefits in stroke risk reduction and in the development of new cases of diabetes. In the analysis of the subgroup of 1,195 patients with hypertension and diabetes included in the LIFE study, losartan had a special prognostic benefit. One of the cardiovascular events included as a primary endpoint was observed in 18% of the losartan-treated patients and in 23% of the atenolol-treated patients (24% relative risk reduction, p = 0.031). The LIFE trial showed that losartan produced better cardiovascular protection than atenolol, a similar blood pressure reduction, and was better tolerated. This drug seems to confer extra cardiovascular protection in addition to reducing blood pressure.
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PMID:[Beyond blood pressure reduction in the treatment of arterial hypertension. Clinical implications of the LIFE study]. 1223 16

Treatment of HIV infection with potent combination antiretroviral therapy has resulted in major improvement in overall survival, immune function and the incidence of opportunistic infections. However, HIV infection and treatment has been associated with the development of metabolic complications, including hyperlipidaemia, diabetes mellitus, hypertension, lipodystrophy and osteopenia. Safe pharmacological treatment of these complications requires an understanding of the drug-drug interactions between antiretroviral drugs and the drugs used in the treatment of metabolic complications. Since formal studies of most of these interactions have not been performed, predictions must be based on our understanding of the metabolism of these agents. All HIV protease inhibitors are metabolised by and inhibit cytochrome P450 (CYP) 3A4. Ritonavir is the most potent inhibitor of CYP3A4. Ritonavir and nelfinavir also induce a host of CYP isoforms as well as some conjugating enzymes. The non-nucleoside reverse transcriptase inhibitor delavirdine potently inhibits CYP3A4, whereas nevirapine and efavirenz are inducers of CYP3A4. Drug interaction studies have been performed with HIV protease inhibitors and HMG-CoA reductase inhibitors. Coadministration of ritonavir plus saquinavir to HIV-seronegative volunteers resulted in increased exposure to simvastatin acid by 3059%. Atorvastatin exposure increased by 347%, but exposure to active atorvastatin increased by only 79%. Conversely, pravastatin exposure decreased by 50%. Similar results have been obtained with combinations of simvastatin and atorvastatin with other HIV protease inhibitors. Thus, the lactone prodrugs simvastatin and lovastatin should not be used with HIV protease inhibitors. Atorvastatin may be used with caution. Although there are no formal studies available, calcium channel antagonists and repaglinide may have significant interactions and toxicity when used with HIV protease inhibitors because of their metabolism by CYP3A4. Sulfonylurea drugs utilise mainly CYP2C9 for metabolism, and this isoenzyme may be induced by ritonavir and nelfinavir with a resulting decrease in efficacy of the sulfonylurea. Losartan may have increased effect when coadministered with ritonavir and nelfinavir because of the induction of CYP2C9 and the expected increase in formation of the active metabolite, E-3174. Overall, well-designed drug-drug interaction studies at steady state are needed to determine whether antiretroviral drugs may be safely coadministered with many of the drugs used in the treatment of the metabolic complications of HIV infection.
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PMID:Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. 1240 66

Type 2 diabetes is the leading cause of end-stage renal disease (ESRD) in most industrialized countries in Europe. The RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) Study evaluated the renal protective effects of losartan versus placebo on a background of non-ACE-I/non-AIIA conventional antihypertensive therapy in 1513 patients with type 2 diabetes and nephropathy. Losartan reduced the incidence of doubling of serum creatinine, end-stage renal disease (ESRD), or death by 16% (P=0.022) and reduced the risk of progression to ESRD, defined as the initiation of dialysis or transplantation, by 29% (P=0.002). We set out to estimate the potential effect of losartan on the burden and costs associated with ESRD over 3.5 years in the European Union (EU). The risk reduction in new cases of ESRD was calculated by combining type 2 diabetes population estimates for the EU with the percent absolute risk reduction of ESRD in patients treated with losartan as observed in RENAAL. The number of days each patient experienced ESRD was defined as the length of time from onset of ESRD until the minimum of death or 3.5 years. ESRD-free person-years avoided with losartan treatment were calculated by combining the population estimate with the ESRD days avoided divided by number of days in a year. ESRD costs from Germany were used to approximate the potential cost savings from reduced time with ESRD and fewer ESRD cases on a EU wide basis. There are approximately 700,000 diagnosed type 2 diabetes patients with proteinuria (urine albumin/creatinine >or=300 mg/g) in the EU. The addition of losartan to the treatment regimen of these patients is expected to lead to a reduction of 44,100 cases of ESRD, 64,400 fewer person-years with ESRD, and reduce ESRD-related costs by euro 2.6 billion over 3.5 years based on RENAAL data. Treatment with losartan not only reduced the incidence of ESRD, but also can result in substantial cost savings in the European Union.
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PMID:Losartan reduces the burden and cost of ESRD: public health implications from the RENAAL study for the European Union. 1241 Aug 59

Individuals with hypertension need to stay on therapy with antihypertensive medication to obtain the full benefits of blood pressure reduction. There are important differences in tolerability across antihypertensive drug classes, and these differences influence the extent to which patients are willing to continue taking their drugs. Three separate sources of evidence--postmarket surveillance studies, medical/prescription database studies, and discontinuation of study medication in long-term endpoint clinical trials--support the proposition that angiotensin II antagonists, the newest class of antihypertensives, are well tolerated, and that patients whose initial treatment is an angiotensin II antagonist are more likely to persist with therapy than patients who use other classes of antihypertensives. Recent landmark trials with losartan in hypertensive patients with left ventricular hypertrophy (Losartan Intervention For Endpoint reduction [LIFE]) and in diabetes (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL]) demonstrated excellent tolerability, a high level of persistence, and clinical benefits exceeding those provided by blood pressure control alone for the prototype angiotensin II antagonist in clinical settings.
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PMID:Compliance and persistence with newer antihypertensive agents. 1241 70

Because treating hypertension in the elderly so effectively reduces major cardiovascular events, it is vital to diagnose this very common condition early. Much of the hypertension that occurs with aging results from stiffening of the major capacitance arteries, typically marked by high systolic and low diastolic blood pressures. Pulse pressure, derived by subtracting diastolic from systolic values, is a useful index of stiffness, but new noninvasive techniques for measurement of arterial compliance have shown that blood pressures cannot reliably predict the state of the arteries in older people. The Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe (Syst-Eur) trial demonstrated that treating hypertension in the elderly with diuretics or calcium channel blockers reduces strokes and cardiac events; these results are also clearly evident in high-risk groups like diabetics. Further analysis of Syst-Eur has suggested that a calcium channel blocker reduces new-onset dementia, while follow-up data from SHEP indicate that a diuretic provides survival and stroke benefits in obese or overweight elderly hypertensives, but not in the lean. In general, comparisons of antihypertensive agents, including diuretics, beta blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers have found similar clinical end point effects. But recently, the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study, performed in patients (average age, 67) with left ventricular hypertrophy and predominant systolic hypertension, showed that the angiotensin receptor blocker losartan was significantly more effective than the beta blocker atenolol in reducing such key outcomes as strokes and new-onset diabetes. Even so, careful but effective control of blood pressure in elderly patients, including those over age 80, still remains a critical factor in preventing major cardiovascular events.
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PMID:Outcomes of treating hypertension in the elderly: a short commentary on current issues. 1250 10

When ACE inhibitors are used to lower blood pressure to the same degree as beta-adrenoceptor antagonists or calcium channel blockers, ACE inhibitors do not seem to have additional benefits to these agents. In the Losartan Intervention for End Point Reduction in Hypertension study (LIFE), losartan was compared to atenolol in hypertensives with the additional risk factor of left ventricular hypertrophy (LVH). For similar effects on blood pressure, losartan had a greater benefit on the primary composite end point (cardiovascular mortality, stroke and myocardial infarction) than atenolol in the hypertensives with LVH, including a prespecified subgroup of patients with additional diabetes mellitus. Losartan also had a greater ability to reverse LVH than atenolol. Thus, losartan should become the standard treatment for hypertension when LVH is present.
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PMID:Losartan for LIFE in hypertension with left ventricular hypertrophy? 1193 79

Little is known about baroreflex control of renal nerve sympathetic activity (RSNA) or the effect of angiotensin II (ANG II) on the baroreflex in diabetes. We examined baroreflex control of RSNA and heart rate (HR) in conscious, chronically instrumented rats 2 wk after citrate vehicle (normal) or 55 mg/kg iv streptozotocin (diabetic) before and after losartan (5 mg/kg iv) or enalapril (2.5 mg/kg iv). Resting HR and RSNA were lower in diabetic versus normal rats. The range of baroreflex control of HR and the gain of baroreflex-mediated bradycardia were impaired in diabetic rats. Maximum gain was unchanged. The baroreflex control of RSNA was reset to lower pressures in the diabetic rats but remained otherwise unchanged. Losartan decreased mean arterial pressure (MAP) and increased HR and RSNA in both groups but had no influence on the baroreflex. Enalapril decreased MAP only in normal rats, yet the increase in HR and RSNA was similar in both groups. Thus in diabetic rats enalapril produced a pressure-independent increase in HR and RSNA. Enalapril exerted no effect on the baroreflex control of HR or RSNA in either group. These data indicate that in conscious rats resting RSNA is lower but baroreflex control of RSNA is preserved after 2 wk of diabetes. At this time, the baroreflex control of HR is already impaired and blockade of endogenous ANG II does not improve this dysfunction.
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PMID:Effect of blockade of endogenous angiotensin II on baroreflex function in conscious diabetic rats. 1252 45


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