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

The aim of this study was to evaluate the action of trandolapril on blood glucose control and microalbuminuria in mild to moderate hypertensive in patients with non-insulin-dependent diabetes. Sixty-seven patients, aged between 33 and 79, were enrolled. After a two week placebo run-in period, treatment with trandolapril as monotherapy was given for 3 months. The dose of trandolapril was adjusted between 1 and 4 mg/day according to antihypertensive response. Patients were assessed clinically and by laboratory investigations each month. Two patients were excluded from efficacy analysis because of major protocol deviations. Mean DBP fell, under the influence of treatment, from 101 +/- 5 mmHg to 82 +/- 7 mmHg (p < 0.0001) and mean SBP from 171 +/- 9 mmHg tp 147 +/- 11 mmHG (p < 0.0001). At three months, 54 patients (84%) had a DBP < or = 90 mmHg. Microalbuminuria decreased significantly (p = 0.03) during treatment. Microalbuminuria returned to normal in 11 of the 13 patients in whom the baseline value was above 21 micrograms/min and increased to above normal in 2 of the 26 patients who had a normal baseline value. Blood glycosylated hemoglobin, fructosamine, glucose and creatinine, and creatinine clearance remained stable. Plasma potassium rose slightly in 7 patients. Six adverse events were reported (4 coughs, 1 peripheral edema, 1 plantar mal perforans). One patient died from pulmonary embolism. In conclusion, trandolapril is an effective antihypertensive agent in hypertensive diabetics. Trandolapril causes a significant decrease in microalbuminuria and does not interfere with blood glucose control in these patients.
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PMID:[Action of trandolapril on the blood glucose balance and microalbuminuria in hypertensive diabetics]. 817 83

Diabetic nephropathy is a major cause of chronic renal failure. The evidence available indicates that renal hemodynamics are altered in clinical and experimental diabetes mellitus. In these circumstances, an increased glomerular filtration rate (GFR) is associated with albuminuria and eventually with glomerulosclerosis. We studied the renal and hemodynamic effects of long-term treatment (5 months) using an angiotensin-converting enzyme inhibitor (trandolapril, 0.7 mg/g b.w. per day) and a calcium antagonist (verapamil, 20 mg/g b.w. per day), and the combination of the two (veratran) at the same dose, on streptozotocin-diabetic uninephrectomized rats. A moderate degree of hyperglycemia (2-4 g/l) was maintained with daily insulin. Mean arterial pressure (MAP) was measured monthly using the tail-cuff method. Determinations were made of urinary protein excretion, creatinine clearance, urinary electrolyte excretion and, at the end of treatment, renal and cardiac hypertrophy. MAP was similar in control and untreated diabetic rats. Trandolapril and veratran reduced MAP whereas verapamil alone had no effect on these animals. All groups showed a slight proteinuria that increased with verapamil treatment. The GFR of diabetic animals was higher than in the control group (mainly the first 2 months), except for veratran group, in which it was similar to the control value. Urinary electrolyte excretion increased in all diabetic groups with no significant differences among them. Veratran induced a protective effect against cardiac hypertrophy. None of the treatments affected renal hypertrophy. It is concluded that in a murine model of diabetes without hypertension or proteinuria, a combination of verapamil and trandolapril prevents hyperfiltration whereas verapamil alone increases proteinuria.
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PMID:Renal effects of antihypertensive therapy in uninephrectomized diabetic rats. 944 Jan 38

The TEAM trial investigated the effectiveness and tolerance of a fixed combination of the ACE inhibitor and calcium channel blocker (2 mg trandolapril and 180 mg verapamil retard) (preparation Tarka) in an open multicentre prospective study of treatment of moderately severe hypertension (diastolic pressure at the end of the two-week wash-out period 100-115 mm Hg). The trial comprised 163 patients who were treated first for four weeks by a monotherapy with 2 mg trandolapril. After these four weeks patients who attained normal blood pressure proceeded with trandolapril treatment. Hypertensive patients who did not attain normal diastolic pressure levels were treated for another four weeks by a fixed combination of trandolapril and verapamil SR. After four weeks of treatment with trandolapril 62 patients of 163 (37%) had a diastolic blood pressure of less than 90 mm Hg. The fixed combination of trandolapril and verapamil SR reduced the diastolic blood pressure to less than 90 mm Hg in 71.6% of the patients resistant to treatment with 2 mg trandolapril and in another 15.6% of patients it reduced the diastolic blood pressure by 10 mm Hg or more. After two months of treatment 60 patients had a normal blood pressure due to trandolapril (37%) and another 73 patients (45%) treated by a combination of trandolapril and verapamil SR, i.e. a total of 133 patients (82%) who originally suffered from moderately severe hypertension, attained a normal diastolic blood pressure. The mean decrease of diastolic pressure after two months of treatment was 19.5 mm Hg in "non-respondents" to trandolapril monotherapy and 23.6 mm Hg in "respondents". The mean decrease of systolic pressure in "non-respondents" and "respondents" after trandolapril treatment was 19.5 mm Hg and 35.0 mm Hg resp. The fixed combination of trandolapril and verapamil was not only effective but was associated with a minimum of undesirable effects. The incidence of headaches declined significantly. The combination of the above preparations is useful also because both preparations have a cardio- and nephroprotective effect and do not affect the lipid and carbohydrate metabolism. Treatment with a fixed combination of trandolapril and verapamil SR is indicated in moderately severe hypertension not responding to monotherapy, in particular when associated with diabetes, hyperlipoproteinaemia, ischaemic heart disease or left ventricular hypertrophy.
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PMID:[The TEAM study--a study of the effectiveness and tolerance of treatment of essential hypertension with a fixed combination of trandolapril and verapamil]. 982 54

The INternational VErapamil SR-Trandolapril study (INVEST) had 6400 of 22,576 (28.3%) participants with diabetes at entry. The objectives of this prespecified analysis were to compare antihypertensive treatment strategies in the diabetes cohort (verapamil SR-based [n=3169] versus atenolol-based [n=3231]) and identify predictors for the primary outcome (a composite of first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke). During a mean follow-up of 2.7 years, 913 participants with diabetes experienced a primary outcome event, with no significant difference between treatment strategies (14.6%, verapamil SR versus 13.9%; atenolol hazard ratio, 1.05; 95% confidence interval, 0.92 to 1.19). Risk for the primary outcome increased with presence of baseline heart failure, renal impairment, US residency, age, previous stroke/transient ischemic attack, previous myocardial infarction, peripheral vascular disease, or smoking. High systolic and diastolic pressures during follow-up also were associated with increased risk, as were low diastolic pressures. Antihypertensive treatment with a verapamil SR or atenolol strategy resulted in similar rates of cardiovascular outcomes in coronary artery disease (CAD) patients with diabetes. Thus, a verapamil SR-based antihypertensive treatment strategy is an alternative to a beta-blocker-based strategy in adults with CAD and diabetes.
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PMID:Clinical outcomes in the diabetes cohort of the INternational VErapamil SR-Trandolapril study. 1536 99

Although numerous prospective randomized trials since the Veterans Administration studies clearly have attested to the efficacy and safety of antihypertensive therapy, there remain some controversial issues with all classes of antihypertensive drugs. Thiazide diuretics increase the risk for new-onset diabetes and their long-term safety has been questioned. Alpha-blockers do not reduce morbidity and mortality in uncomplicated hypertension but are well known to cause a variety of poorly tolerated side effects. The safety of calcium antagonists has been questioned for many years, although recent large prospective randomized trials such as Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, International Verapamil-Trandolapril Study, Intervention as a Goal in Hypertension, Valsartan Antihypertensive Long-Term Use Evaluation and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) have attested to their safety and efficacy. Angiotensin-converting enzyme inhibitors, in general, are well tolerated but have potentially fatal adverse effects in a few patients. Angiotensin-receptor blockers are exceedingly well tolerated, but may be less-efficacious antihypertensive agents than other drug classes. Most antihypertensive drug classes have an effect on new-onset diabetes that should be taken into account in patients at risk. No head-to-head comparison of combination therapy looking at efficacy and safety has been available. The long-term safety of antihypertensive therapy is documented poorly because most trials only last 4 to 6 years. Despite these drawbacks and concerns, the benefits of antihypertensive therapy clearly outweigh its potential risk.
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PMID:Therapeutic controversies in hypertension. 1620 95

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.
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PMID:Trandolapril/verapamil combination in hypertensive diabetic patients. 1758 77

Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.
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PMID:Managing hypertension in diabetic patients--focus on trandolapril/verapamil combination. 1796 76

Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.
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PMID:Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study. 1832 72

Metabolic syndrome (MS), typified by hypertension, abdominal obesity, dyslipidaemia and impaired glucose metabolism, is a precursor of type 2 diabetes. Thiazide diuretics (TD) and beta-blockers are associated with increased risk of diabetes in patients with hypertension; however, the role of these agents in development of diabetes in MS patients is unknown. We reviewed the literature regarding risk factors for diabetes development and compared this with data from the Study of Trandolapril/Verapamil SR And Insulin Resistance (STAR), which investigated the effects of two fixed-dose combinations (FDCs) [trandolapril/verapamil SR and losartan/hydrochlorothiazide (L/H)] on glucose control and new diabetes in MS patients. In STAR, logistic regression modelling identified haemoglobin A1c [odds ratio (OR) 4.21 per 1% increment; p = 0.003), L/H treatment (OR 4.04; p = 0.002) and 2-h oral glucose tolerance test glucose levels (OR 1.39 per 10 mg/dl increments; p < 0.001) as baseline predictors of diabetes. These data support prior analyses and suggest that choice of antihypertensive agent is important. Patients with MS may be at lower risk of diabetes when using a FDC calcium channel blocker + angiotensin-converting enzyme inhibitor compared with an angiotensin receptor blocker + TD.
Diabetes Obes Metab 2009 Mar
PMID:Risk factor assessment for new onset diabetes: literature review. 1856 74

Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI significantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration.
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PMID:Update on the use of trandolapril in the management of cardiovascular disorders. 1933 28


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