UMLS:C0028754 - FACTA Search

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Query: UMLS:C0028754 (obesity)
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Hypertension is currently defined in terms of levels of blood pressure associated with increased cardiovascular risk. A cut-off of 140/90 mm Hg is accepted as a threshold level above which treatment should at least be considered. This would give a prevalence of hypertension of about 20% of the adult population in most developed countries. Hypertension is associated with increased risk of stroke, myocardial infarction, atrial fibrillation, heart failure, peripheral vascular disease and renal impairment. Hypertension results from the complex interaction of genetic factors and environmental influences. Many of the genetic factors remain to be discovered, but environmental influences such as salt intake, diet and alcohol form the basis of nonpharmacological methods of blood pressure reduction. Investigation of the individual hypertensive patient aims to identify possible secondary causes of hypertension and also to assess the individual's overall cardiovascular risk, which determines the need for prompt and aggressive therapy. Cardiovascular risk can be determined from (i) target organ damage to the eyes, heart and kidneys; (ii) other medical conditions associated with increased risk; and (iii) lifestyle factors such as obesity and smoking. Secondary causes of hypertension are individually rare. Screening tests should be initially simple, with more expensive and invasive tests reserved for those in whom a secondary cause is suspected or who have atypical features to their presentation. The main determinants of blood pressure are cardiac output and peripheral resistance. The typical haemodynamic finding in patients with established hypertension is of normal cardiac output and increased peripheral resistance. Treatment of hypertension should initially use nonpharmacological methods. Selection of initial drug therapy should be based upon the strength of evidence for reduction of cardiovascular mortality in controlled clinical trials, and should also take into account coexisting medical conditions that favour or limit the usefulness of any given drug. Given this approach, it would be reasonable to use a thiazide diuretic and/or a beta-blocker as first-line therapy unless there are indications to the contrary. Individual response to given drug classes is highly variable and is related to the underlying variability in the abnormal pathophysiology. There are data to suggest that the renin-angiotensin system is more important in young patients. The targeting of this system in patients under the age of 50 years with a beta-blocker (or ACE inhibitor), and the use of a thiazide diuretic (or calcium antagonist) in patients over 50 years, may enable blood pressure to be controlled more quickly.
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PMID:Pathoaetiology, epidemiology and diagnosis of hypertension. 1067 92

Fifty patients with diabetes of long duration -20 to 35 years-who followed regimens to control the disease with the greatest fidelity did not have visual complaints; retinal abnormalities were minimal and hypertension, albuminuria and renal impairment were absent. Diabetes is a disease of total metabolism and not related solely to carbohydrate. In the preinsulin era many facts concerned in the regulation of diabetes were established scientifically-facts such as that regulation of the body mass and control of obesity are important, that damage is caused by over-restriction of carbohydrate intake, and that hyperglycemia activates diabetes. Many failures in the treatment today are owing to insufficient attention to these basic factors. Good control requires an effort to keep hyperglycemia and glycosuria at a minimum.
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PMID:Diabetes mellitus and diabetic retinitis; factors influencing regulation. 1303 94

Hypertension is common among patients with type 2 diabetes mellitus, increasing their risk of cardiovascular morbidity and mortality. Such patients are also at risk of renal impairment and end-stage renal disease. Long-term, tight blood pressure control (ideally to a target of < 130/85 mmHg) in patients with type 2 diabetes is a highly effective strategy for reducing the risk of cardiovascular complications and is now embodied in the many guidelines of hypertension and diabetes management. More recent studies indicate that the choice of antihypertensive agent is also important. Drugs that block the renin-angiotensin-aldosterone system, such as the angiotensin-II receptor blockers (ARBs), may prevent the onset of diabetes and confer greater cardiovascular benefit among patients who already have this disease compared with some older antihypertensive agents. For example, in type 2 diabetic patients with renal dysfunction, ARBs exert a renal protective effect that extends beyond blood pressure reduction and may retard diabetic nephropathy. Antihypertensive therapy, together with lifestyle modification to address obesity and physical inactivity, can significantly reduce the risk of cardiovascular complications in patients with type 2 diabetes. The challenge is to achieve beneficial, hygienic measures in populations with diverse backgrounds and improve compliance with proven treatments that inevitably involve multiple drugs. Combination therapies comprising agents that offer good tolerability and do not exacerbate existing metabolic disturbances, as well as demonstrating benefit in preventing events in diabetic patients beyond blood pressure reduction itself, seem a likely way forward.
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PMID:Benefits of blood pressure reduction in diabetic patients. 1451 49

The equation developed from the MDRD (Modification of Diet in Renal Disease) study provides more accurate estimate of GFR than other commonly used equations. The aim of this study was to compare prediction of GFR based on MDRD and Cockcrof-Gault (CG) method. The study was performed in 111 patients (mean age 42 +/- 5 years) with chronic renal impairment (Scr = 281 +/- 83 micromol/l). The mean of MDRD was 0.480 +/- 0.345 ml/s/1.73 m2 and that of CG 0.608 +/- 0.336 ml/s/1.73 m2. The difference is highly significant (p < 0.0001). The mean of CG/MDRD ratio was 1.24 +/- 0.17. This ratio was significantly higher (p < 0.01) in obese patients (1.59 +/- 0.14 vs 1.22 +/- 0.09). The CG/MDRD ratio did not show relation to Scr. The results are in keeping with the assumption that the difference between MDRD and CG method cannot be explained by increased tubular secretion of creatinine in residual nephrons. Obesity seems to be on of the factors responsible for the difference between CG and MDRD values.
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PMID:[A new method to estimate glomerular filtration rate based on serum concentration of creatinine, urea and albumin (MDRD, Modification of Diet in Renal Disease)]. 1532 57

Type 2 diabetes mellitus is a progressive and complex disorder that is difficult to treat effectively in the long term. The majority of patients are overweight or obese at diagnosis and will be unable to achieve or sustain near normoglycaemia without oral antidiabetic agents; a sizeable proportion of patients will eventually require insulin therapy to maintain long-term glycaemic control, either as monotherapy or in conjunction with oral antidiabetic therapy. The frequent need for escalating therapy is held to reflect progressive loss of islet beta-cell function, usually in the presence of obesity-related insulin resistance. Today's clinicians are presented with an extensive range of oral antidiabetic drugs for type 2 diabetes. The main classes are heterogeneous in their modes of action, safety profiles and tolerability. These main classes include agents that stimulate insulin secretion (sulphonylureas and rapid-acting secretagogues), reduce hepatic glucose production (biguanides), delay digestion and absorption of intestinal carbohydrate (alpha-glucosidase inhibitors) or improve insulin action (thiazolidinediones). The UKPDS (United Kingdom Prospective Diabetes Study) demonstrated the benefits of intensified glycaemic control on microvascular complications in newly diagnosed patients with type 2 diabetes. However, the picture was less clearcut with regard to macrovascular disease, with neither sulphonylureas nor insulin significantly reducing cardiovascular events. The impact of oral antidiabetic agents on atherosclerosis--beyond expected effects on glycaemic control--is an increasingly important consideration. In the UKPDS, overweight and obese patients randomised to initial monotherapy with metformin experienced significant reductions in myocardial infarction and diabetes-related deaths. Metformin does not promote weight gain and has beneficial effects on several cardiovascular risk factors. Accordingly, metformin is widely regarded as the drug of choice for most patients with type 2 diabetes. Concern about cardiovascular safety of sulphonylureas has largely dissipated with generally reassuring results from clinical trials, including the UKPDS. Encouragingly, the recent Steno-2 Study showed that intensive target-driven, multifactorial approach to management, based around a sulphonylurea, reduced the risk of both micro- and macrovascular complications in high-risk patients. Theoretical advantages of selectively targeting postprandial hyperglycaemia require confirmation in clinical trials of drugs with preferential effects on this facet of hyperglycaemia are currently in progress. The insulin-sensitising thiazolidinedione class of antidiabetic agents has potentially advantageous effects on multiple components of the metabolic syndrome; the results of clinical trials with cardiovascular endpoints are awaited. The selection of initial monotherapy is based on a clinical and biochemical assessment of the patient, safety considerations being paramount. In some circumstances, for example pregnancy or severe hepatic or renal impairment, insulin may be the treatment of choice when nonpharmacological measures prove inadequate. Insulin is also required for metabolic decompensation, that is, incipient or actual diabetic ketoacidosis, or non-ketotic hyperosmolar hyperglycaemia. Certain comorbidities, for example presentation with myocardial infarction during other acute intercurrent illness, may make insulin the best option. Oral antidiabetic agents should be initiated at a low dose and titrated up according to glycaemic response, as judged by measurement of glycosylated haemoglobin (HbA1c) concentration, supplemented in some patients by self monitoring of capillary blood glucose. The average glucose-lowering effect of the major classes of oral antidiabetic agents is broadly similar (averaging a 1-2% reduction in HbA1c), alpha-glucosidase inhibitors being rather less effective. Tailoring the treatment to the individual patient is an important principle. Doses are gradually titrated up according to response. However, the maximal glucose-lowering action for sulphonylureas is usually attained at appreciably lower doses (approximately 50%) than the manufacturers' recommended daily maximum. Combinations of certain agents, for example a secretagogue plus a biguanide or a thiazolidinedione, are logical and widely used, and combination preparations are now available in some countries. While the benefits of metformin added to a sulphonylurea were initially less favourable in the UKPDS, longer-term data have allayed concern. When considering long-term therapy, issues such as tolerability and convenience are important additional considerations. Neither sulphonylureas nor biguanides are able to appreciably alter the rate of progression of hyperglycaemia in patients with type 2 diabetes. Preliminary data suggesting that thiazolidinediones may provide better long-term glycaemic stability are currently being tested in clinical trials; current evidence, while encouraging, is not conclusive. Delayed progression from glucose intolerance to type 2 diabetes in high-risk individuals with glucose intolerance has been demonstrated with troglitazone, metformin and acarbose. However, intensive lifestyle intervention can be more effective than drug therapy, at least in the setting of interventional clinical trials. No antidiabetic drugs are presently licensed for use in prediabetic individuals.
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PMID:Oral antidiabetic agents: current role in type 2 diabetes mellitus. 1566 80

Gouty arthritis, a common source of pain and disability, is the most common form of inflammatory arthritis affecting older people. The authors review the epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical forms of gouty arthritis. Gout is part of a clinical spectrum of conditions (obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need for better patient education on management of these associated conditions is emphasized. The general algorithm of gout management is presented. Clinical particularities of gout presentation in older patients (increased incidence in women, polyarticular onset with hand involvement, earlier development of tophi, association with use of diuretics) are reviewed. Barriers against an optimal control of gout include lack of patient education, presence of comorbid conditions, particularly renal impairment, use of multiple drugs such as diuretics, and cognitive decline. Gout management in older adults remains unsatisfactory.
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PMID:Gouty arthritis. A primer on late-onset gout. 1602 79

Oral anticoagulant therapy with vitamin K antagonists (VKAs) such as warfarin has proven benefits in the treatment and prevention of thromboembolic disorders but has important limitations that result in substantial underuse. In particular, the VKAs have variable and unpredictable pharmacokinetics and pharmacodynamics and a narrow separation between antithrombotic and hemorrhagic effects that necessitates careful dose adjustment based on frequent coagulation monitoring. In contrast, the oral direct thrombin inhibitor ximelagatran has a predictable and reproducible pharmacokinetic/pharmacodynamic profile that allows treatment using fixed-dose regimens without coagulation monitoring. The bioavailability of melagatran, the active form of ximelagatran, after oral administration of ximelagatran is approximately 20% with low inter- and intra-individual variability. Peak plasma melagatran concentrations are reached approximately 2 hours after oral dosing of ximelagatran to healthy volunteers, and melagatran is eliminated with a half-life of approximately 3 hours with clearance predominantly by renal excretion. Hence, a higher melagatran exposure is seen in patients with renal failure; ximelagatran is currently not recommended for patients with severe renal impairment (creatinine clearance of <30 mL/min) as these patients were not included in the clinical trial program. Exposure to melagatran increases linearly with the ximelagatran dose. The pharmacokinetic/pharmacodynamic profile is consistent across a broad range of different patient populations and is unaffected by gender, age, body weight, ethnic origin, obesity, and mild-to-moderate hepatic impairment. Any differences in melagatran pharmacokinetics associated with these factors are attributable to differences in renal function.
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PMID:Pharmacokinetics and pharmacodynamics of ximelagatran. 1612 11

Elderly patients require special consideration when administered anticoagulants because of age-related alterations in renal function, protein binding, and increased bleeding risk. Unfractionated heparin can be used in most patients but difficulties with dosing and monitoring often lead to inadequate anticoagulation. Low-molecular-weight heparin has more predictable pharmacokinetics than conventional heparin, but requires dose adjustments in renal impairment and obesity. Fondaparinux is a synthetic pentasaccharide that is being used increasingly for both treatment and prophylaxis of venous thromboembolism. The immune-mediated form of heparin-induced thrombocytopenia is a syndrome with thrombocytopenia or thrombosis in the setting of heparin use. Heparin-induced thrombocytopenia must be identified early, and treated with argatroban or lepirudin to avoid life-threatening complications.
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PMID:Heparins, low-molecular-weight heparins, and pentasaccharides. 1637 64

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor. Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined. Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone. Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function. Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.
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PMID:Gout in solid organ transplantation: a challenging clinical problem. 1639 75

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.
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PMID:Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. 1648 81

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