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)

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipid-lowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipid-lowering drug (fenofibrate) with an additional hypouricaemic effect.
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PMID:Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia: case histories. 1119 Oct 5

The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic challenge. Newer therapeutic approaches may be sought in the fields of immunosuppression, nonspecific supportive measures, heparinoid administration, and removal of a supposed glomerular basement membrane toxic factor. In immunosuppression, the newer drugs now used in organ transplantation (cyclosporine, tacrolimus, and mycophenolate mofetil) can also be used in the treatment of glomerulonephritis. In nonspecific supportive treatment, angiotensin II receptor antagonists are now used in addition to angiotensin-converting enzyme inhibitors. Positive effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on the nephrotic syndrome have not yet been proven. Cyclooxygenase II inhibitors must be tested but probably have too many renal side effects, similar to those of nonsteroidal anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions and thus have protective effects on the negative charge of the glomerular basement membrane. They can now be administered as oral medications. The removal of a supposed glomerular basement membrane toxic factor that induces proteinuria has been attempted for 20 yr and now is usually performed using immunoadsorption. Especially in cases of recurrent nephrotic syndrome after renal transplantation for patients with glomerulonephritis, this approach has been successful in decreasing proteinuria, although in most cases its effect is not lasting but must be continuously renewed.
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PMID:New aspects of the treatment of nephrotic syndrome. 1125 Oct 31

Diabetic nephropathy, which develops in about 30% of patients with diabetes, is a progressive condition. It is characterized by increased blood pressure, declining glomerular filtration rate and albuminuria. Lowering of blood pressure in diabetic patients is associated with reduced cardiovascular risk and renal protection. Inhibitors of angiotensin-converting enzyme (ACE) are the current gold standard treatment for hypertension in patients with type I diabetes because, in addition to their blood pressure lowering ability, they are thought to oppose the increased intraglomerular pressure that is mediated in part by angiotensin II. The angiotensin II receptor antagonists, a more recently developed class of antihypertensive agents, appear to be as effective as ACE inhibitors in delaying the progression of renal injury in animal models of diabetes. They act by selectively blocking the binding of angiotensin II to the AT1 receptor and may, therefore, offer a more complete blockade of the renin-angiotensin system than ACE inhibitors. The renal and antihypertensive effects of this class of drug in patients with diabetes are now being investigated in long-term clinical trials. The multicentre Diabetics Exposed to Telmisartan And EnalaprIL (DETAIL) study is a randomized, double-blind, parallel-group comparison of the renal and antihypertensive effects of the angiotensin II receptor antagonist telmisartan and the ACE inhibitor enalapril in 272 patients with type II diabetes. The primary outcome is change in glomerular filtration rate over the 5 years of the study.
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PMID:The role of angiotensin II receptor antagonists in the management of diabetes. 1133 10

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT 1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.
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PMID:Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension. 1133 83

Many antihypertensive drugs are available to treat patients with essential hypertension. Japanese Society of Hypertension (JSH) recently published 'Guidelines for the management of Hypertension (JSH 2000)'. JSH 2000 chooses six drugs(calcium antagonist, angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist, diuretic, beta-blocker, alpha-blocker) as first lines of antihypertensive treatment. These six drugs have different pharmacological characteristics and there are compelling indications for specific drugs in certain clinical conditions such as diabetes mellitus, organ damages, and elderly hypertensives etc. Usually a low dose of the initial drug choice should be used. The optimal formulation should provide 24-hour efficacy with a once-daily dose, because compliance is better and control of hypertension is persistent and smooth.
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PMID:[Pharmacological characteristics and choice of antihypertensives]. 1139 91

Diabetic nephropathy has become the leading cause of terminal renal failure in all Western nations due to a steady increase of patients with the renal complication of type 2 (non-insulin-dependent) diabetes mellitus. A number of modifiable risk factors have been identified that predispose to and/or accelerate renal disease in patients with diabetes mellitus. Among these, the level of blood pressure, even in the range of normotension according to World Health Organization or Joint National Committee definition, is closely related to the rate of progression of diabetic nephropathy. This has been documented in patients with incipient (microalbuminuric) and in patients with manifest (proteinuric) diabetic renal disease. Consequently, the treatment of even normotensive diabetics has been recommended once microalbuminuria is present, and blood pressure values in the low normal range should be aimed for. The selection of antihypertensive agents is also important, however, since a 'renoprotective effect' has been documented for drugs that interfere with the renin-angiotensin-aldosterone system such as angiotensin converting enzyme inhibitors. Recently, a new class of drugs that selectively inhibits this system by specifically targeting the angiotensin II receptor has been developed. These angiotensin II subtype 1-receptor antagonists are efficacious antihypertensive agents with a side-effect profile similar to placebo. Evidence for a renoprotective effect in patients with diabetic nephropathy from a large controlled clinical trial is still awaited, but data generated in animal experiments and in smaller clinical trials are encouraging. Currently, these drugs are a valuable substitute for angiotensin converting enzyme inhibitors in patients who experience side effects such as intractable cough.
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PMID:Angiotensin II subtype 1-receptor antagonists in the treatment of diabetic nephropathy. 1145 Dec 16

Cardiovascular and renal diseases in diabetes stem from an accelerated form of atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a clinical hallmark of microangiopathy and often leads to end-stage renal failure. Significantly, microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in both the diabetic and non-diabetic population. In diabetic patients, it is also strongly associated with proliferative retinopathy, neuropathy and hypertension. Effective blood pressure reduction in patients with type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay the progression of diabetic nephropathy, postpone renal failure and improve survival. These benefits have been demonstrated with a variety of blood pressure-lowering agents, including beta-blockers, calcium channel blockers, diuretics and angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal effects of the newest class of antihypertensive agents, the angiotensin II receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides antihypertensive efficacy comparable to ACE inhibitors but with superior tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations (PRIME) is an important morbidity and mortality program encompassing the Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is evaluating the effects of irbesartan in preventing diabetic nephropathy and end-stage renal failure and in reducing cardiovascular events in high-risk hypertensive patients with type 2 diabetes. The trials were completed at the end of 2000.
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PMID:Hypertension and diabetes: the scope of the problem. 1146 14

The pathogenesis of hypertension in diabetes type 1 and type 2 is different. Diabetic nephropathy is regarded as the most essential factor contributing to the development of hypertension in patients with diabetes mellitus type 1. Obesity, insulin resistance and hyperinsulinaemia are responsible for hypertension in diabetes mellitus type 2. In both types of diabetes, hypertension is involved in fast progress of diabetic renal disease. Antihypertensive treatment in diabetic patients should include: non-pharmacological interventions, drug-therapy, regular blood pressure monitoring, educational efforts. ACE-inhibitors, calcium antagonists, diuretics, beta-blockers, angiotensin II receptor antagonists and alpha 1-blockers are used as antihypertensive agents in diabetic patients. Neutral endopeptidase inhibitors are the new, promising therapeutic option.
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PMID:[Hypertension in patients with diabetes mellitus--selected pathogenetic and therapeutic aspects]. 1147 57

With increasing case reports, it has been indicated that some cases with adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) show abnormal responses in cortisol to various stimulation tests. Here we report a case of AIMAH that showed an aberrant response to angiotensin II via AT1 receptor in cortisol hypersecretion. A 53-yr-old man was admitted to our division seeking further examinations for the possible diagnosis of Cushing's syndrome. He had hypertension, diabetes mellitus, and physical stigmata, such as moon face and central obesity. His plasma ACTH level was undetectable, and plasma cortisol level was high. Plasma cortisol showed no normal diurnal rhythm and was not suppressed after the administration of 8 mg of dexamethasone. Abdominal computed tomography demonstrated nodular enlargement of bilateral adrenal glands. He was diagnosed with Cushing's syndrome owing to AIMAH. An injection of arginine vasopressin (AVP) increased plasma cortisol and aldosterone levels, whereas ACTH remained undetectable. After 4 h in an upright position, plasma cortisol and aldosterone levels were increased. Pretreatment with candesartan, angiotensin II receptor AT1 antagonist, blocked the increase in plasma cortisol level. These results suggested a possibility of adrenal hypersensitivity to angiotensin II and AVP in cortisol secretion. Bilateral laparoscopic adrenalectomy was performed. The histological findings of the specimen were compatible with AIMAH. In summary, we have made the first report on a case of AIMAH with possible hypersensitivity to angiotensin II.
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PMID:Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with possible adrenal hypersensitivity to angiotensin II. 1157 27

A prospective, randomized, three-armed, double-blind, placebo-controlled clinical trial has been completed in 210 sites worldwide to determine whether the angiotensin II receptor blocker irbesartan or the calcium channel blocker amlodipine has a renoprotective effect in patients with overt type 2 diabetic nephropathy. A total of 1,715 subjects randomized during a 3-year period were followed a minimum of 2 years. The goal for all treatment groups was to achieve equivalent blood pressure control, with the blinded study drug (irbesartan, amlodipine, or placebo) as primary therapy with additional antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, calcium antagonists, and angiotensin II receptor antagonists, to achieve seated systolic blood pressure less than 135 mm Hg and diastolic blood pressure less than 85 mm Hg. The primary outcome was the combined endpoint of time to doubling of entry serum creatinine, end-stage renal disease, or death. Secondary outcomes included fatal and nonfatal cardiovascular events. A Clinical Management Committee monitored the conduct of the study. An Outcome Confirmation Committee classified all study outcome events in blinded fashion. An external Data Safety Monitoring Committee monitored unblinded data for interim safety and efficacy analyses of the study. Eligibility criteria included informed consent, age 30 to 70 years, adult-onset diabetes, hypertension, urine protein excretion greater than 900 mg/24 hours, and serum creatinine values of 90 to 265 micromol/L in women and 110 to 265 micromol/L in men. Baseline characteristics were age, 59 +/- 8 years; body mass index, 31 +/- 7 kg/m(2); 67% male; 73% white, 14% black, and 13% other; duration of diabetes, 15 +/- 9 years; retinopathy, 66%; neuropathy, 48%; congestive heart failure, 7.5%; screening seated systolic blood pressure, 156 +/- 18 mm Hg, and diastolic blood pressure, 85 +/- 11 mm Hg; urine protein excretion, 4.0 +/- 3.5 g/24 hours; serum creatinine, 150 +/- 53 micromol/L; serum potassium, 4.6 +/- 0.5 mEq/L; total cholesterol, 229 +/- 58 mg/dL; and hemoglobin A(1c), 8.1 +/- 1.7%. This large-scale international trial should help define the clinical course and standards of care for hypertensive adults with type 2 diabetes mellitus and nephropathy. Results available on May 19, 2001, will help in defining the current controversy of the risks and benefits of blockade of the renin-angiotensin system versus calcium channel blockade versus standard antihypertensive therapy in this large patient population.
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PMID:A clinical trial in type 2 diabetic nephropathy. 1157 53


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