UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Without treatment, about 60% of atrial arrhythmia patients suffer a relapse within 3 months and 70% within one year. Antiarrhythmic treatment intended to reduce this percentage is therefore justified, on condition that it is well tolerated. Several preliminary questions have to be settled before this medical prophylaxis: 1) Justification of antiarrhythmic treatment (sometimes pointless to deal with very occasional episodes); 2) Treatment of the underlying heart disease (valve disease, cardiothyrotoxicosis, etc.) or promoting factors (potassium depletion etc.); 3) Accurate assessment of any associated conduction abnormalities, which may constitute a contraindication to antiarrhythmic treatment (WPW syndrome in the case of verapamil and the digitalis-like drugs) or require additional treatment (pacemaker); 4) Definition of the mechanism (vagal or sympathotonic) inducing arrhythmia; 5) Evaluation of the hemodynamic parameters of the underlying heart disease (size of the atria, ventricular function, coronary or valvular lesions) which may limit the efficacy of the treatment. Once these parameters have been identified, the primary treatment should be type la or lb antiarrhythmics, which have been shown to be effective, despite the fact that they are not without arrhythmic risks (the Ib antiarrhythmics are less effective and have a poor safety profile). The beta-blockers have preferential indications (hypersympatheticotonia, hyperthyroidism, hypertrophic myocardiopathy, mitral prolapse, angina etc.) and can be replaced by verapamil or bepridil if there are non-cardiac contraindications (ulcers, asthma, diabetes). Amiodarone is extremely effective, but its poor extracardiac safety restricts its long-term use. Complementary treatments (digitalis-like, anticoagulants or anti-PAF and cardiostimulant drugs) should be added if necessary. Recurrences (to be confirmed by ECG or Holter) should lead to rigorous confirmation of therapeutic compliance and observance of simple hygienic and dietary measures (no excessive exertion, elimination of stimulants etc.). With strict clinical and ECG monitoring, it would then be possible either to increase the dose levels (accompanied by plasma determinations if possible) or to switch to a treatment with more effective, but more aggressive drugs (amiodarone, flecainide) or to use drug associations (la and lb, la and II etc.). Repeated failure of such attempts should lead to a non-medical approach to treatment.
...
PMID:[Preventive drug therapy of recurrence of atrial fibrillation]. 129 92

To determine the relations of diet with risk of clinical noninsulin-dependent diabetes, we analyzed data from a prospective cohort of 84360 US women. During 6 y of follow-up we identified 702 definite incident cases. Because body mass index (BMI) is a powerful risk factor for diabetes, we examined the relations of fat (including type), fiber, sucrose, and other components of diet to risk of diabetes, among women with BMIs (in kg/m2) less than 29 kg/m2. After controlling for body mass index, previous weight change, and alcohol intake, we observed no associations between intakes of energy, protein, sucrose, carbohydrate, or fiber and risk of diabetes. Compared with women in the lowest quintile of energy-adjusted intake, and relative risks (and tests for trend) for those in the highest quintile were 0.61 (P trend = 0.03) for vegetable fat, 0.62 (P trend = 0.008) for potassium, 0.70 (P trend = 0.005) for calcium, and 0.68 (P trend = 0.02) for magnesium. These inverse associations were attenuated among obese women (BMIs greater than or equal to 29).
...
PMID:Diet and risk of clinical diabetes in women. 131 20

Although inhibition of Na(+)-K+ ATPase has been described in the diabetic heart, K+ loss from myocardium has not been observed in a canine model of mild diabetes. The finding of tissue Na+ accumulation and a potential relation to alteration of left ventricular inositol as observed in other tissues in diabetes form the basis of this investigation. Diabetes was induced with alloxan in three groups of male mongrel dogs who were studied after 1 yr. In the initial experiment the tissue compartment volumes, determined with intravenous 51Cr EDTA as a marker, were found to be normal. Calculated cell sodium was increased to 32.8 +/- 2.6 mEq/kg cell H2O vs 18.7 +/- 1.1 in controls (p < 0.01). Cell potassium in diabetes was normal. In the second group, myocardial polyols were analyzed by gas-liquid chromatography. Inositol was diminished in diabetes to 0.61 +/- 23 microM/g of left ventricle, vs the respective control levels of 1.9 +/- 0.57 microM/g (p < 0.02). Sorbitol concentration was unaltered. Left ventricular sodium increments were not associated with altered tissue calcium. In group III the hypothesis that inhibition of Na(+)-K+ ATPase in diabetes might not elicit the expected alteration of K+ transport was assessed during intracoronary infusion of acetyl strophanthidin. No difference in cation responses from control was observed. It is postulated that a change in the conformation of Na(+)-K+ ATPase, with high affinity sodium binding sites facing the intracellular compartment, may render sodium less releasable from cell membrane.
...
PMID:Myocardial inositol and sodium in diabetes. 133 48

Although corticosteroid treatment is clearly beneficial to patients with temporal arteritis, its exact risk/benefit ratio in these old and side effects-prone patients is unknown. We have thus surveyed that available French and English literature, in order to pool the published series and to evaluate the iatrogenic potential of corticosteroids in this situation. We selected 11 series, yielding a total of 1008 patients. A treatment failure resulted in the death of the patient in five cases. Twenty-seven patients became blind, but only 2 under treatment. The side-effects involved 29% of the patients and are responsible of 29 deaths (2.9%): osteoporosis was the main problem, followed by femoral head necrosis and muscle wasting. Gastroduodenal ulcers were uncommon and generally benign; sigmoid colon diverticulitis was infrequent but dangerous; some infectious complications were noted (herpes zoster, tuberculosis, etc...); high blood pressure and diabetes were common problems. Psychiatric side-effects were rare. Thus, the unwanted effects of corticosteroids in the treatment of temporal arteritis are relatively infrequent and generally not severe, except osteoporosis. They should be systematically prevented by appropriate diet and treatments (e.g., calcium, potassium, and vitamin D supplements).
...
PMID:[Benefits of corticosteroids in the treatment of Horton's disease and rhizomelic pseudopolyarthritis: advantages and inconveniences. A meta-analysis]. 134 39

Transgenic mice with elevated levels of beta-cell calmodulin develop severe diabetes even though pancreatic beta-cells contain reserve levels of insulin. Electron microscopic examination of transgenic pancreas confirmed the presence of abundant insulin secretory granules and failed to reveal obvious morphological abnormalities. These observations suggested that excess calmodulin may specifically impair the secretory process. To directly assess the effect of excess calmodulin on beta-cell function we have isolated pancreatic islets from transgenic animals. Transgenic islets from 6- to 8-day-old mice used 40% less glucose than normal islets and contained 58% of the normal insulin content, 90% of the normal glucagon content, and 5-fold higher levels of calmodulin than islets from control mice of the same age. Parallel perifusions of normal and transgenic islets confirmed that excess calmodulin inhibited glucose-stimulated insulin secretion; first phase secretion was reduced by 60%, and second phase secretion was essentially absent. Static assays were performed to assess the response to other secretagogues. All fuel secretagogues tested were ineffective in stimulating insulin secretion from transgenic islets. Secretion in response to depolarizing levels of potassium was also severely impaired. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine increased transgenic secretion, but not to the level obtained in normal islets. Of the compounds examined, only phorbol 12-myristate 13-acetate and carbachol, two substances thought to act in beta-cells by stimulation of protein kinase-C, produced equivalent secretion in normal and transgenic islets. Phorbol 12-myristate 13-acetate also appeared to restore second phase secretion in transgenic islets. These results indicate that the initial period of calmodulin-induced diabetes is due to a secretory defect. This defect appears to be distal to membrane depolarization and is selective for the second phase of insulin secretion.
...
PMID:Elevated beta-cell calmodulin produces a unique insulin secretory defect in transgenic mice. 137 47

To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor-operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an acceleration in atherosclerosis.
...
PMID:Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus. 137 44

The question, of whether long-term treatment of essential hypertension with angiotensin-converting enzyme (ACE) inhibitors is capable of modifying glucose tolerance or insulin sensitivity in Type 2 (non-insulin dependent) diabetes, is still unsolved. We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period and again after 3 months of antihypertensive treatment with the ACE inhibitor, captopril. Glucose tolerance was tested with a 75-g oral glucose load and insulin sensitivity was measured by the insulin suppression test, while dietary and drug treatment of the diabetes remained constant. In the whole group, mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123 +/- 3 mmHg to a final value of 115 +/- 2 mmHg (p < 0.005); in six patients, the change in MBP was < 5 mmHg (non-responders), thus giving a clinical response rate of approximately 60%. After treatment, fasting plasma glucose, insulin, free fatty acid (FFA), potassium, and glycated haemoglobin concentrations were unchanged from baseline. During the oral glucose tolerance test, the incremental glucose area-under-curve was 0.75 +/- 0.05 mol 120 min l-1 before and 0.76 +/- 0.06 mol 120 min l-1 after treatment (p = ns). Endogenous insulin response and suppression of plasma FFA levels were superimposable on the two occasions. During the insulin suppression test, steady-state plasma glucose levels were 14.4 +/- 1.3 vs 14.2 +/- 1.1 mmol l-1 before and after chronic ACE inhibition, respectively, at comparable hyperinsulinaemic plateaux (291 +/- 21 vs 287 +/- 14 pmol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of chronic ACE inhibition on glucose tolerance and insulin sensitivity in hypertensive type 2 diabetic patients. 139 66

Analysis of the available evidence indicates that diuretics do not increase coronary heart disease morbidity and mortality. The multiclinic trials supporting the cardiotoxicity hypothesis are few in number and flawed in design. The majority of the trials, including the well designed trials, indicate no excess of coronary heart disease (CHD) events in diuretic-treated patients compared with those given other drugs or placebo. Recent studies indicate no increase in cardiac arrhythmias after diuretic treatment. Also, although depletion of intracellular potassium and magnesium occurs in patients with congestive heart failure even without diuretics, intracellular concentration of these ions is not significantly reduced by diuretics in patients with uncomplicated hypertension. Modest elevations of serum cholesterol may occur during the first 6 to 12 months of treatment with thiazide diuretics. However, after this time these elevations fall to or below the pretreatment level. The fall may be greater in patients receiving other drugs but the differences are small and their clinical significance is questionable. The incidences of hyperglycaemia and diabetes were only minimally increased in long term clinical trials while the importance of hyperinsulinism and insulin resistance in causing CHD remains unproven in patients. Thiazides remain, therefore, a safe and effective treatment for patients with hypertension.
...
PMID:Adverse effects of diuretics. 141 93

Diuretics have long been recognized to increase the concentration of some atherogenic plasma lipids and to reduce insulin sensitivity and adversely influence carbohydrate tolerance, but the mechanisms responsible have not been conclusively established. Early studies reporting diabetes in diuretic-treated patients implicated potassium loss as responsible. More recent observations have extended this suggestion by also demonstrating a role for the renin-angiotensin-aldosterone system. In addition, direct effects of antihypertensive agents on insulin sensitivity have been demonstrated; both hormonal and haemodynamic factors have been implicated. Diuretic-induced lipid changes have also been consistently observed, but the mechanisms for these findings are much less clear. A link between the carbohydrate and insulin alterations and those of lipids has been suggested. Plasma catecholamine concentration may also be increased by diuretics and it is possible that this may also influence lipid metabolism. While the mechanisms of these metabolic effects of diuretics are not yet clearly established, useful clues based on dose relationships and susceptible populations can be discerned. Observations from combination drug therapies also provide additional information regarding potential mechanisms. The availability of new drug therapies associated with few metabolic changes further suggest that effective diuretic therapy need not always be associated with significant adverse metabolic changes.
...
PMID:Mechanisms of diuretic effects on carbohydrate tolerance, insulin sensitivity and lipid levels. 148 6

Hypertension, dyslipidaemia, glucose intolerance (associated with insulin resistance and compensatory hyperinsulinaemia) and other abnormalities are complementary coronary risk factors which often occur in association. A familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism which can be detected before the appearance of hypertension. Diabetes mellitus as well as obesity promotes the development of hypertension and dyslipidaemia. Moreover, certain drugs used for antihypertensive therapy can further modify lipoprotein and glucose metabolism. Thiazides in high dosage and loop-diuretics can increase serum low-density-lipoprotein cholesterol (LDL-C) and/or very-LDL-C and the total C/high-density lipoprotein cholesterol (HDL-C) ratio, while HDL-C is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidaemia is dose-dependent and low thiazide doses (i.e. hydrochlorothiazide < or = 12.5 mg daily) are less active, awaits clarification. The diuretic-antihypertensive agent, indapamide, given at a dose of 2.5 mg.day-1, seems to exert no relevant effect on serum lipoprotein or glucose metabolism. The potassium-sparing diuretic, spironolactone, also may be largely neutral with regard to lipids. Moreover, potassium sparing diuretics may possibly counteract, at least in part, a dyslipidaemic influence of potassium-loosing diuretics in medium dose. Drug-induced dyslipidaemia, as well as glucose intolerance, represent potentially adverse influences. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but a lesser decrease in coronary events.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of diuretics on the plasma lipid profile. 148 8

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>