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)

The goal of medical treatment during acute cerebral infarction is to enhance thrombolysis and inhibit the chemical alterations associated with cell death. Treatment includes avoidance of blood pressure reduction, blood glucose control, possible anticoagulation with IV heparin, and sometimes reduction of cerebral edema. Optimal treatment thereafter depends on the result of patient evaluation. Uncontrolled vascular risk factor (eg, hypertension, smoking, and diabetes) should be treated. Aspirin and ticlopidine reduce the risk of recurrent ischemic stroke. In patients with nonrheumatic atrial fibrillation, anticoagulation with warfarin reduces the risk of embolic events. Carotid endarterectomy is superior to medical management alone in reducing the risk of stroke in patients with > 70% symptomatic extracranial carotid stenosis.
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PMID:Ischemic stroke, Part 2: Optimal treatment and prevention. 844 20

Non-enzymic glycosylation (glycation) of structural proteins has been widely studied as a possible mechanism in the long-term complications of diabetes. Here we show that glycation inactivates malate dehydrogenase. Aspirin affords some protection against the glycation, but alpha-crystallin, a lens protein which appears to act as a molecular chaperone in other systems, is much more effective. For example, 5 mM glucose completely inactivates malate dehydrogenase in four days, and 5 micrograms alpha-crystallin/ml provides complete protection against this inactivation. Fructose, a superior glycating agent, inactivates the enzyme in 24 hours but even so the same low concentration of alpha-crystallin is able to protect 80% of the activity. Other proteins provide no protection at the same concentration. The inactivation of malate dehydrogenase and other enzymes by glycation could play a role in diabetic complications, and molecular chaperones like alpha-crystallin could serve to protect them.
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PMID:Glycation-induced inactivation of malate dehydrogenase protection by aspirin and a lens molecular chaperone, alpha-crystallin. 861 56

The annual incidence of ischemic stroke among patients with chronic non-valvular atrial fibrillation is about 4.5 percent. In five controlled trials, oral anticoagulant therapy with warfarin reduced the annual incidence of stroke by 68 percent to 1.4 percent. The effect of aspirin has not been unequivocally determined. Aspirin reduced the annual risk of stroke by 18 percent (n.s.) in one trial, and by 44 percent in another, though the two trials differed both in mean age of the patients and in aspirin doses. Direct comparison of warfarin and aspirin revealed no difference in efficacy. Advanced age, previous stroke or transient ischemic attack (TIA), hypertension and diabetes were all found to be risk factors for stroke in patients with atrial fibrillation. In patients under 65 years of age without risk factors, the annual risk of stroke was 1 percent. After TIA or minor stroke, warfarin reduced the annual risk of a second stroke from 12 percent to 4 percent. Aspirin had no such effect. The annual incidence of major bleeding episodes was 0.2-2.0 percent in the warfarin-treated subgroup, 0.2-1.5 percent in the aspirin subgroup and 0-1.6 percent in the placebo subgroup. Based on findings in the above mentioned trials, warfarin (INR 2.0-3.0) is recommended for stroke prevention in patients over 60 years of age with non-valvular atrial fibrillation. Trials are under way to ascertain whether conventional warfarin treatment can be replaced by less complicated and safer treatments in patients with chronic atrial fibrillation.
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PMID:[Atrial fibrillation and apoplexy--risks and prevention]. 870 Jun 41

In nonthyroidal illness, numerous drugs such as glucocorticoids, dopamine, fenclofenac, furosemide and diphenylhydantoin may modify the close inverse-feedback relationship between circulating thyroid hormones and TSH. Such effects could involve altered hypothalamic TRH secretion, a direct effect on TSH production by the thyrotroph, alterations in circulating free thyroid hormone concentrations, or changes in thyroid hormone uptake by the thyrotroph. We therefore examined the effect of nonsteroidal antiinflammatory drugs (NSAID), diuretics, the synthetic flavonoid EMD 21388, and diphenylhydantoin, on [125I]T3 cellular uptake in rat pituitary primary cell cultures. Uptake of [125I]T3 (cell-associated counts of washed cells) was measured at 15 min after the addition of 50 pmol/L [125I]T3 in protein-free medium (37 degrees C, pH 7.4). Uptake of [125I]T3 by pituitary cells was 6.0 +/- 1.7% of total counts (mean +/- SD, n = 18). Unlabeled T3 (10 mumols/L) displaced 92% of total uptake. The IC50 of unlabeled T3 for the displacement of [125I]T3 was 1.2 mumols/L. T4 and rT3 were approximately 10% as effective as T3 itself in inhibiting [125I]T3 uptake, while triac did not affect cellular [125I]T3 uptake. Inhibition of [125I]T3 uptake at drug concentrations of 100 mumols/L was seen with the diuretics, furosemide (9%), bumetanide (14%), piretanide (12%) and ethacrynic acid (76%), the NSAID, meclofenamic acid (35%) and fenclofenac (52%), EMD 21388 (49%), and the anticonvulsant, diphenylhydantoin (23%). Aspirin, up to 500 mumols/L, had no effect on [125I]T3 uptake. Our results indicate that ethacrynic acid, meclofenamic acid, fenclofenac, EMD 21388 and diphenylhydantoin affect plasma membrane T3 uptake in the pituitary. This potential influence on TSH release will be contrary to the previously-demonstrated direct inhibitory effect of these drugs on TSH release.
Exp Clin Endocrinol Diabetes 1996
PMID:Drug effects on triiodothyronine uptake by rat anterior pituitary cells in vitro. 874 Sep 39

The role of cyclo-oxygenase and or its substrate(s) on the neuroactivity of evening primrose oil was investigated on the basis that a blockade of cyclo-oxygenase activity using aspirin would inhibit neuroactivity of primrose oil if this effect was mediated by prostanoids. Streptozotocin diabetic rats and controls were all given large doses of aspirin, but only subgroups of them received primrose oil. Saphenous sensory A- and C-fibre, and sciatic motor conduction velocities were measured to assess neuroactivity of primrose oil. Aspirin enhanced the neuroactivity of primrose oil thus indicating that prostanoids are unlikely to mediate this neuroactivity, but also suggesting that substrates of cyclo-oxygenase are neuroactive. It is likely that cyclo-oxygenase antagonises neuroactivity of primrose oil by competing with the process for substrates. Thickly myelinated sensory A-fibres were most affected by primrose oil suggesting that the predominant sensory symptoms in diabetic neuropathy could be due to the sensitivity of sensory nerves to the metabolic aberration in diabetes. Normal nerve function is probably preserved by cyclo-oxygenase during an influx of neuroactive fatty acids from the gut, since inhibition of the enzyme rendered non-diabetic nerves vulnerable to dietary primrose oil.
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PMID:Endogenous cyclo-oxygenase substrates mediate the neuroactivity of evening primrose oil in rats. 892 93

We compared stroke severity, risk factors, and prognosis in patients with recurrent versus first-ever stroke. In the Copenhagen Stroke Study, we prospectively studied 1,138 unselected patients with acute stroke. Stroke was recurrent in 265 (23%) despite most of these patients being given prophylactic treatment prior to recurrence. Only 12% of patients with atrial fibrillation were receiving anticoagulant treatment prior to recurrence. In multivariate analysis, recurrence was more frequently associated with a history of TIA, atrial fibrillation, male gender, and hypertension, but not with age, daily alcohol consumption, smoking, diabetes, ischemic heart disease, serum cholesterol, or hematocrit. Mortality was almost doubled compared with patients with a first-ever stroke. In survivors, however, both neurologic and functional outcomes and the speed of recovery were, in general, similar in the two groups. Despite similar neurologic impairments, patients with recurrence contralateral to their first stroke had markedly more severe functional disability after completed rehabilitation than patients with ipsilateral recurrence, implying that the ability to compensate functionally is decreased in patients with contralateral recurrence. Our findings emphasize the importance of consistent anticoagulant treatment for stroke patients with atrial fibrillation and close blood pressure control in stroke patients with hypertension. Other prophylactic measures are needed in patients in whom ASA fails to prevent recurrence. Patients with recurrent stroke have a markedly higher mortality than patients with a first-ever stroke, but those who survive recover as well and as fast as patients with a first-ever stroke. However, if recurrence is contralateral to the first stroke, functional recovery is poorer.
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PMID:Stroke recurrence: predictors, severity, and prognosis. The Copenhagen Stroke Study. 910 73

Transesophageal echocardiography visualizes the left atrium, the left atrial appendage, thrombi and spontaneous echo contrast within them. The role of these findings as predictors for embolism in atrial fibrillation is unknown. We performed transesophageal echocardiography in 409 non-rheumatic atrial fibrillation outpatients (62 +/- 12 years, 36% female) with no recent (< 1 year) history of embolism. Patients with left atrial/appendage thrombi received oral anticoagulation, those without thrombi Aspirin. The patients were followed up over 2 years. Primary events were stroke, embolism and non stroke/embolism related deaths. Secondary events were initiation of anticoagulation in patients primarily assigned to Aspirin. Left atrial/appendage thrombi were diagnosed in 2.5%. They were associated with diabetes, heart failure and decreased left ventricular fractional shortening (p < 0.05 for each variable). Spontaneous echo contrast was diagnosed in 12%. It was associated with increased age, constant atrial fibrillation, hypertension, heart failure, valvular abnormalities and increased left atrial diameter (p < 0.05 for each variable). Increased left atrial appendage size was associated with constant atrial fibrillation, etiology of atrial fibrillation and valvular abnormalities (p < 0.05 for each variable). Follow-up was 25 +/- 7 months. 29 patients suffered a stroke, 33 further patients died of non stroke/embolism related causes. Secondary events occurred in 19 patients. Neither left atrial/appendage thrombi nor left atrial appendage size were predictors for embolism. Predictors for embolism were increased age (p = 0.003), hypertension (p = 0.01) and increased diastolic blood pressure (p = 0.04). In non-rheumatic atrial fibrillation outpatients with no recent history of embolism, transesophageal echocardiography is of limited value to assess embolic risk. Hypertension and increased diastolic blood pressure have been confirmed in their significance as clinical predictors for embolism.
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PMID:[Embolism in left-atrial thrombi (ELAT Study): are spontaneous echo contrast, thrombi in the left atrium/appendage and size of the left atrial appendage predictors of possible embolisms?]. 913 72

Appropriate prevention and management of coronary heart disease (CHD) requires an integrated approach to the reduction of risk factors. These principally include reduction of elevated lipids, control of blood pressure, and cessation of smoking. In addition, appropriate exercise, diet, and weight reduction (where necessary) are also important. Control of diabetes and stress management may also be helpful. Aspirin therapy is appropriate for all patients with known CHD and selected patients without CHD who have several risk factors, including nonmodifiable risk factors such as age, a positive family history, and male gender.
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PMID:Nonlipoprotein risk factors for coronary heart disease: evaluation and management. 921 80

People with Type 2 (non-insulin-dependent) diabetes mellitus die mainly from cardiovascular and cerebrovascular disease. Furthermore, the major burden of their symptoms arise from arterial disease, including peripheral vascular disease. However, management guidelines for Type 2 diabetes continue to focus on blood glucose control, which is only one of a number of arterial risk factors found with this type of diabetes. Clinically it is evident that blood glucose control continues to occupy centre-stage in the management of Type 2 diabetes as practised by many physicians. Even when arterial risk factors such as smoking or raised serum triglycerides are noted, their management is often relatively neglected. As part of the St Vincent Declaration Action Programme, a working group has sought consensus on the number and relative importance of arterial risk factors requiring management in quality diabetes care. The group seeks to assist those devising protocols and guidelines, records and quality systems, and those charged with directly advising and educating people with diabetes. Arterial risk factors that can be routinely identified and monitored, and modified by application of management protocols, include high blood pressure, high serum total and LDL cholesterol, low serum HDL cholesterol and raised serum triglycerides, poor blood glucose control, smoking, high body mass index and body fat distribution. Aspirin can modify hypercoagulability, but this is not easily monitored. Arterial risk factors that cannot be modified, but which have an impact on the intensity of management of other factors, include ethnic group, gender, and family history of arterial disease. Raised albumin excretion is an arterial risk factor and can be modified, but it is not clear whether this reduces cardiovascular risk. For many of the risk factors, levels of high, medium, and low risk can be set. These can be used, in consultation with the patient, to determine appropriate interventions and provide feedback on risk reduction resulting from successful management.
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PMID:A strategy for arterial risk assessment and management in type 2 (non-insulin-dependent) diabetes mellitus. European Arterial Risk Policy Group on behalf of the International Diabetes Federation European Region. 947 70

Several glucose transporters have recently been identified in glomeruli, and in cultured glomerular cells. These include the facilitative glucose transporter isoforms GLUTs 1, 3 and 4, and sodium-glucose cotransport activity with characteristics of SGLT1. GLUTs 1, 3 and 4 are all high affinity, low capacity, facilitative glucose transporters which typically would be saturated at or near physiologic glucose concentrations. The SGLT transporter of mesangial cells is also a high affinity transporter which similarly could be saturated under normal glucose conditions. This suggests that in order for mesangial cells to take up excessive quantities of glucose in diabetes, changes in glucose transporter expression, translocation or activity may be required. Accordingly, recent investigations discovered positive-feedback regulation of the mesangial cell GLUT1 transporter by glucose, and a regulatory role for GLUT1 in glucose metabolism and extracellular matrix synthesis. Future investigations of glucose transporters in the pathogenesis of diabetic renal disease will now likely proceed in multiple directions, including but not limited to: (1) examination of their regulation by growth factors implicated in diabetic nephropathy, and the resultant effects on ECM synthesis; (2) determination of the mechanisms by which GLUT1 regulates the expression of aldose reductase, PKC, GLUT1, and other genes in the mesangial cell; and (3) Suppression of glucose transporters in attempts to prevent high glucose-induced diabetic glomerulosclerosis.
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PMID:Glucose transporters of the glomerulus and the implications for diabetic nephropathy. 928 9


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