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

Heart failure is one of the commonest debilitating conditions of industrialized society, with mortality and morbidity comparable with that of the common neoplastic diseases. The role of beta-blockers in heart failure has been the subject of debate for many years. The results of recent prospective, placebo-controlled studies of the addition of beta-blockers to standard therapy in patients with chronic heart failure have confirmed a significant beneficial effect on ventricular function, clinical status, morbidity and mortality. The importance of these trials suggests that beta-adrenergic blocker therapy can save one life out of every 35 patients treated with mild-to-moderate heart failure. These major trials have used one of four beta-blockers (metoprolol, bisoprolol, carvedilol, or bucindolol) in varying study designs with different patient populations. Beta-blockers improve function of the failing left ventricle, prevent or reverse progressive left ventricular dilation, chamber sphericity, and hypertrophy, and consequently have a positive impact on cardiac remodeling. Beta-blockers also reduce heart rate and left ventricular wall stress, leading to reduced myocardial oxygen consumption, a clear benefit to the failing heart. Moreover, beta-blockers can improve the intrinsic contractile function of cardiomyocytes and have been shown to improve myocardial energetics in heart failure, possibly through desirable changes in substrate utilization. Many important clinical questions still remain unanswered. These questions include whether beta-blockers are of benefit in patients with severe NYHA functional class (IIIB-IV), in patients with asymptomatic left ventricular dysfunction, in the extreme elderly, in patients with diabetes mellitus and renal impairment. Furthermore, it is not clear whether beta-blockade by itself is the real mechanism of clinical benefit. Although certain effects of beta-blockers may be considered class effects, it is not yet clear whether there are differences between beta 1-selective antagonists and nonselective agents. Major studies are currently being undertaken to address the above questions.
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PMID:[Critical analysis of beta blockers in heart failure: certainty and incompleteness]. 1099 6

Patients with hypertension do not comprise a homogeneous group, and the majority present with a variety of concomitant and associated conditions. Antihypertensive therapies should therefore be effective and well tolerated in a wide range of patients and should, ideally, ameliorate the negative target-organ effects of hypertension, such as atherosclerosis, cardiovascular remodelling and renal impairment. Evidence is accumulating that the new angiotensin II type 1 receptor blocker, candesartan cilexetil, lowers blood pressure effectively and is well tolerated in a variety of patient groups, including women and the elderly. In patients with severe hypertension, a treatment schedule based on candesartan cilexetil, with the addition of diuretic and calcium antagonist therapy as needed, has been found to control blood pressure successfully. Candesartan cilexetil does not affect glucose tolerance or lipid profiles in patients with diabetes mellitus, and it is not associated with any of the side effects of other antihypertensive agents that would make it unsuitable for use in patients with pulmonary disease. Initial clinical studies have indicated that candesartan cilexetil is well tolerated and effective in patients with heart failure. Furthermore, the available evidence shows that treatment with candesartan cilexetil can reverse the negative effects of hypertension on left ventricular hypertrophy and microalbuminuria. It therefore appears that the pronounced efficacy and placebo-like tolerability of candesartan cilexetil, as demonstrated in large clinical trials of patients with mild to moderate hypertension, can be extended to a wide range of specific patient groups.
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PMID:Efficacy and tolerability of candesartan cilexetil in special patient groups. 1105 33

Repaglinide (NovoNorm((R))) is a novel oral antidiabetic agent, the first of a new class of insulin secretagogues known as the prandial glucose regulators to be approved for use in patients with Type 2 diabetes. Prandial glucose regulation is aimed at restoring the first-phase insulin response that follows consumption of a meal, which is missing in patients with Type 2 diabetes. After repaglinide administration, the resulting insulin profile reflects that of healthy individuals more closely, providing tighter glycaemic control and reducing the risk of hypoglycaemic events. Repaglinide is quickly absorbed and rapidly eliminated through biliary excretion, making it suitable for use in patients with renal impairment. It appears in the bloodstream within 15 to 30 min of dosing, stimulating short-term insulin release from the pancreatic beta-cells by binding to a unique site on the beta-cell membrane. Rapid elimination ensures that postprandial insulin levels quickly return to preprandial levels as the high prandial glucose level subsides. Repaglinide is given on a 'one meal, one tablet; no meal, no tablet' basis. It is particularly effective in patients who have not previously been treated with an oral antidiabetic agent, significantly reducing glycosylated haemoglobin (HbA(1c)) levels by 1.6%. It also offers increased mealtime flexibility and safety, compared with other oral antidiabetic agents. As a result of the short plasma half-life and lack of accumulation of repaglinide with repeated dosing, the risk of between-meal and nocturnal hypoglycaemia is substantially reduced compared with other oral antidiabetic agents. Repaglinide acts synergistically with metformin, consistently improving glycaemic control in patients who were insufficiently controlled by metformin alone. Results from recent studies have shown similar synergistic effects with neutral protamine Hagedorn (NPH)-insulin or troglitazone.
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PMID:Pharmacology and clinical experience with repaglinide. 1106 Jul 17

The majority of patients with acute coronary syndromes have renal impairment from either the aging process or from underlying disease, such as nephrosclerosis or diabetes. For example, in the phase 3 studies of bivalirudin use in PTCA, only 25% of patients had normal renal function: 46% had mild renal impairment, 28% had moderate renal impairment and about 1% had severe renal impairment. In patients with normal renal function, the intravenous pharmacokinetics of bivalirudin are dose proportional (linear) and are characterized by rapid plasma clearance (4.58 ml/minute/kg), a small volume of distribution (0.2 L/kg), and an elimination half-life of about 30 minutes. Renal clearance is the primary route of elimination of bivalirudin. As for other small polypeptides, bivalirudin is filtered at the glomerulus, secreted in the proximal convoluted tubule, reabsorbed in the distal convoluted tubule and degraded within intracellular lysosomes to constituent amino acids. There is a direct positive relationship between the dose of bivalirudin, plasma concentrations and the activated partial thromboplastin time (aPTT) or activated clotting time (ACT). A study comparing the pharmacokinetics and pharmacodynamics of bivalirudin with normal renal function (GFR greater than or = 90 ml/minute; n = 8), mild (GFR 60-89 ml/minute; n = 8), moderate (GFR 30-59 ml/minute; n = 7), or severe (GFR < 30 ml/minute; n = 10) renal impairment showed that while clearance was similar in the normal (4.58 ml/minute/kg) and mildly impaired (4.94 ml/minute/kg) groups, the clearance rate was reduced 45% in the moderate impairment (2.50 ml/minute/kg) group and about 68% in the severe impairment (1.46 ml/minute/kg) group. Clearance was further reduced (77%) in a group of 12 dialysis dependent patients (1.04 ml/minute/kg). There was a strong positive correlation between plasma bivalirudin concentrations and aPTT. The derived maximal effect (Emax) was similar for the normal (58.3 seconds), mildly impaired (44.7 seconds) and moderately impaired (56.8 seconds) groups, but prolonged in the severely renally impaired (79.4 seconds) and dialysis dependent (84.4 seconds) patients. These kinetic and dynamic results have recently been substantially confirmed in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), where reduced plasma clearance (20%) and elevated ACTs were observed in patients with moderate renal impairment. The bleeding results of the phase 3 PTCA clinical trial (involving 4,312 patients) in which patients were classified as having normal renal function, or mild, moderate or severe renal impairment (using the above criteria), is consistent with the pharmacokinetic data. The incidence of major bleeding was directly correlated with renal function for both bivalirudin (normal, 1.2%; mild, 1.9%; moderate, 6%; severe, 0%) and heparin (normal, 3.1%; mild, 8.5%; moderate, 12.7%; severe, 26.7%). Importantly, the incidence of major bleeding was significantly less on bivalirudin than heparin in patients with any degree of renal impairment. The mean 45-minute ACT values were similar (350-400 seconds) in the normal, mild and moderately impaired groups, but elevated in the severely impaired group (450 seconds). A multivariate analysis of bleeding covariates in this database indicated that GFR is an important risk factor for bleeding (r(2) = 0.054), and accounted for twice the variability in bleeding as either sex or age.
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PMID:The use of bivalirudin in patients with renal impairment. 1115 32

Results of treatment of 18 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Sixteen of the 18 patients (88.8%) had mental status changes, and seven of the 18 patients (38.8%) had renal impairment. One patient had a secondary type of TTP, caused by non-Hodgkin's lymphoma of the large intestine (that was diagnosed later) and was excluded from the study. Immunosuppresive therapy with steroids, plasma exchange and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in a statistically significant increase of platelet count (P = 0.00222), and a significant improvement in consciousness defined by increased GCS after 2 weeks (P = 0.00222). In two patients renal function recovered, and in one of them hemodialysis was no longer needed. This improvement in a small group of patients had no statistical significance. TTP recurred in seven patients. High doses of steroids caused serious side effects in two patients: in one patient, steroid diabetes, and in the other one, intestinal perforation.
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PMID:Possibilities and limits of treatment in patients with thrombotic thrombocytopenic purpura. 1119 78

Prandial glucose regulation represents a new concept in the management of type 2 diabetes: targeting postprandial glycaemic excursions as a means of achieving long-term glycaemic control. Although control of the overall glycaemic load is the most important factor for the success of long-term management of type 2 diabetes, control of postprandial hyperglycaemia also has positive implications for preventing the development of diabetic complications. Repaglinide is the first prandial glucose regulator to become available in the clinical setting. It has a rapid and short-lived insulinotropic action and can therefore reduce postprandial glucose excursions without increasing the risk of hypoglycaemia. Short-term clinical studies showed that repaglinide is superior to glibenclamide in improving postprandial glycaemic control. Longer-term studies confirmed that improved PGR is accompanied by improved overall glycaemic control that is at least equivalent to that achieved by sulphonylurea treatment. Moreover, because repaglinide can be used with flexible meal patterns without compromising glucose control, it can improve quality of life as indicated by overall treatment satisfaction, well-being and health status. Repaglinide has few contraindications or drug interactions and can be used in a wide range of patients. Although careful titration of repaglinide dose is recommended for patients with mild to moderate renal impairment, no dosage adjustment is otherwise needed in the elderly. In addition to being an effective first-line hypoglycaemic agent, repaglinide is highly effective in combination therapy for patients with type 2 diabetes who require more intensive treatment. When glucose targets are not met using repaglinide monotherapy, the combination of repaglinide with metformin can further improve glycaemic control by enhancing insulin secretion and improving insulin sensitivity. Similarly, when required combination of repaglinide with troglitazone or NPH-insulin can produce better glycaemic control than monotherapy alone. Given that most patients with type 2 diabetes require a multitherapy approach to achieve and sustain adequate glycaemic control, repaglinide will be an important element in future intensive therapy regimens.
Diabetes Obes Metab 2000 Mar
PMID:Repaglinide: prandial glucose regulation in clinical practice. 1122 59

Intractable liver allograft rejection remains an important cause of graft loss. In this present study, we evaluated the role of oral FK 506 in 30 rejection episodes resistant to conventional cyclosporin-based triple immunosuppression in a series of 28 patients. Rejection was reversed in 11 (91.7%) of 12 patients for intractable acute rejection and in 10 (58.8%) of 17 patients for chronic rejection. A progressive decline in serum bilirubin was observed within 14 days in those successfully salvaged and a serum bilirubin of less than 200 micromol/l at the time of FK 506 conversion in the chronic rejection subgroup was found to be good predictor of response (specificity 100%, sensitivity 60%). New onset diabetes mellitus (29%) and reversible renal impairment (32%) were the commonest adverse events observed. Eleven (52%) of the responding patients successfully discontinued corticosteroid medication and are currently on FK 506 monotherapy. FK 506 therapy has a significant impact in the control of both intractable acute and chronic allograft rejection with an acceptable toxicity profile.
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PMID:FK 506 rescue therapy for intractable liver allograft rejection. 1127 39

Long-term renal function was compared in 49 liver recipients [25 patients received cyclosporin (CyA) and 24 patients received FK 506] followed for a period of 1 year. Creatinine (CR) and glomerular filtration rate (GFR) pretransplantation (pre-Tx) and at 1, 3, 5, and 12 months post-Tx were recorded, as well as incidences of hyperkalemia, post-Tx hypertension, and insulin-dependent diabetes mellitus (IDDM) in the two groups. At 1 year post-Tx, the mean Cr had risen from baseline by 56% and 60% in the FK and CyA groups, respectively; the mean GFR had dropped by 32% in FK patients and by 27% in CyA patients. Acute nephrotoxicity occurred in 7/25 CyA patients (2/7 required dialysis) and 9/26 FK patients (7/9 required dialysis; 2/7 were switched to CyA). None remained on dialysis at 3 months. Renal insufficiency persisted at 1 year in 7/16 patients with early toxicity (CyA, 4; FK, 3) and in 3 of the remaining 36 pts (P < 0.001). Hyperkalemia occurred in 4/25 CyA, and in 12/24 FK patients (P < 0.025), post-Tx hypertension occurred in 15 CyA, and 7 FK patients (P < 0.05), and IDDM occurred in 4 CyA and 7 FK patients (P = ns). FK 506 and CyA, thus, exerted similar chronic renal effects. Although acute renal insufficiency improved upon dose reduction, renal impairment was permanent in some cases.
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PMID:Comparison of short and long-term renal function in liver transplant patients receiving cyclosporin or FK 506. 1127 40

Initially it was considered that moxonidine, like clonidine, acted at central (2)-adrenoceptors to reduce blood pressure. With the characterisation of imidazoline binding sites distinct from (2)-adrenoceptors, the consensus became that moxonidine was acting predominantly at imidazoline I(1) receptors in the rostral ventrolateral medulla to lower blood pressure. Moxonidine acts at prejunctional (2)-adrenoceptors on sympathetic nerve endings to decrease noradrenaline release and this may contribute to its ability to lower blood pressure. The predominant site of action of moxonidine may also depend on route of administration, with imidazoline I(1) receptors being predominant after central, and (2)-adrenoceptors predominant after systemic administration. The controversy over the mechanism and site of action with moxonidine is ongoing. In animal models, moxonidine lowers blood pressure, reduces cardiac hypertrophy and remodelling, reduces cardiac arrhythmias and increases blood flow in cerebral ischaemia. Moxonidine also has beneficial effects in animal models of diabetes and kidney disease. Moxonidine increases sodium and water excretion in rats, but not humans. Animal studies indicate that moxonidine may be useful in the treatment of glaucoma by reducing intra-ocular pressure. Animal studies show that moxonidine may also be effective in pain and in ethanol withdrawal. In humans, the pharmacokinetics of moxonidine are of the one-compartment model with first-order absorption. Renal elimination is the major route of elimination and individual titration of moxonidine is needed in patients with renal impairment. There is overwhelming evidence that moxonidine is a safe and effective antihypertensive. A large clinical trial of moxonidine in heart failure, MOXCON, was stopped because of excessive deaths in the moxonidine group. Moxonidine should not be used in patients with heart failure, but there are no obvious reasons to stop its use as an antihypertensive, or its development for other clinical uses.
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PMID:Moxonidine: some controversy. 1133 90

We investigated the prevalence of renal impairment in individuals with known hypertension or diabetes aged 50--75 years in two South London General PRACTICES: We initially interrogated the practice and hospital biochemistry databases for each individual's most recent serum creatinine. Individuals with no result recorded in the previous year were then invited for screening: 189/365 (51.8%) attended. Data were collected on 821 of a total potential population of 997. Taking a serum creatinine of 120 mmol/l as the upper limit of normal, the overall prevalence of renal disease in this population was 8.4%: 6.1% in the hypertensives, 12.6% in the diabetics and 16.9% in those with both. Significant proteinuria (> or =2+) was present in 3.9% of the total population: 2.2% of hypertensives, 8.3% of diabetics and 3.9% of those with both. At screening, 44.5% of individuals had inadequately controlled blood pressure. Renal impairment is common in this population at high risk of renal disease. Screening for renal disease in this population is simple, safe and gives a high yield of positive results.
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PMID:Renal impairment in elderly patients with hypertension and diabetes. 1135


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