Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute heart failure syndromes (AHFS) represent the most common discharge diagnosis in patients over age 65 years, with an exceptionally high mortality and readmission rates at 60-90 days. Recent surveys and registries have generated important information concerning the clinical characteristics of patients with AHFS and their prognosis. Most patients with AHFS present either with normal systolic blood pressure or elevated blood pressure. Patients who present with elevated systolic blood pressure usually have pulmonary congestion, a relatively preserved left ventricular ejection fraction (LVEF), are often elderly women, and their symptoms develop typically and abruptly. Patients with normal systolic blood pressure present with systemic congestion, reduced LVEF, are usually younger with a history of chronic HF, and have symptoms that develop gradually over days or weeks. In addition to the abnormal hemodynamics (increase in pulmonary capillary wedge pressure and/or decrease in cardiac output) that characterize patients with AHFS, myocardial injury, which may be related to a decrease in coronary perfusion and/or further activation of neurohormones and renal dysfunction, probably contributes to short-term and post-discharge cardiac events. Patients with AHFS also have significant cardiac and noncardiac underlying conditions that contribute to the pathogenesis of AHFS, including coronary artery disease (ischemia, hibernating myocardium, and endothelial dysfunction), hypertension, atrial fibrillation, and type 2 diabetes mellitus. Therefore, the targets of therapy for AHFS should be not only to improve symptoms and hemodynamics but also to preserve or improve renal function, prevent myocardial damage, modulate neurohumoral and inflammatory activation, and to manage other comorbidities that may cause and/or contribute to the progression of this syndrome.
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PMID:Acute heart failure syndromes: clinical scenarios and pathophysiologic targets for therapy. 1748 81

Heart disease is the leading cause of death in patients with insulin resistance and type 2 diabetes (DM2). Even in the absence of coronary artery disease and hypertension, functional and structural abnormalities exist in patients with well-controlled and uncomplicated DM2. These derangements are collectively designated by the term diabetic cardiomyopathy (DCM). Changes in myocardial energy metabolism, due to altered substrate supply and utilization, largely underlie the development of DCM. Insulin is an important regulator of myocardial substrate metabolism, but also exerts regulatory effects on intracellular Ca2+ handling and cell survival. The current paper reviews the multiple functional and molecular effects of insulin on the heart, all of which ultimately seem to be cardioprotective both under normal conditions and under ischemia. In particular, the dismal consequences of myocardial insulin resistance contributing to the development of DCM will be discussed.
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PMID:Myocardial insulin action and the contribution of insulin resistance to the pathogenesis of diabetic cardiomyopathy. 1755 6

In the recent years, measurement of blood level of fibrinogen has been treated very seriously and this parameter has been considered an individual cardiovascular risk factor. A correlation between serum fibrinogen and the frequency of acute myocardial or cerebral ischemia has been found in a large number of studies. A distinct association between a high fibrinogen level and vascular complications in diabetic patients has been revealed as well. Two types of fibrinogen--high molecular weight fibrinogen (HMWF) weighing 340 kD, and low molecular weight fibrinogen (LMWF), weighing 280 kD and lacking a certain part of A alpha-polypeptide chain, are known today. B. Lipinski created a technique to measure the content of LMWF in blood serum, which made it possible to study the role played by this protein in the clinical presentation of atherothrombosis in diabetic patients. This work presents the results of research into the role of LMWF in the clinical picture of atherothrombosis in patients with type 2 diabetes mellitus. According to the localization of the manifestation of arterial ischemia and the presence of diabetes, three groups ofpatients were formed. The study revealed significantly higher LMWF level in all the three groups compared to controls. The LMWF/total blood fibrinogen ratio was also elevated.
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PMID:[Fibrinogens and their role in atherogenesis in diabetes mellitus]. 1788 12

Coronary artery disease (CAD) accounts for a large fraction of the morbidity, mortality, and cost of diabetes. Recognizing this, nearly 10 years ago the American Diabetes Association published a consensus recommendation that clinicians consider a risk factor-guided screening approach to early diagnosis of CAD in both symptomatic and asymptomatic patients. Subsequent clinical trial results have not supported those recommendations. Since the prior consensus statement, newer imaging methods, such as coronary artery calcium scoring and noninvasive angiography with computed tomography (CT) techniques, have come into use. These technologies, which allow quantitation of atherosclerotic burden and can predict risk of cardiac events, might provide an approach to more widespread coronary atherosclerosis screening. However, over this same time interval, there has been recognition of diabetes as a cardiovascular disease (CVD) equivalent, clear demonstration that medical interventions should provide primary and secondary CVD risk reduction in diabetic populations, and suggestive evidence that percutaneous coronary revascularization may not provide additive survival benefit to intensive medical management in patients with stable CAD. This additional evidence raises the question of whether documenting asymptomatic atherosclerosis or ischemia in people with diabetes is warranted. More data addressing this issue will be forthcoming from the BARI 2-D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Until then, for patients with type 2 diabetes who are asymptomatic for CAD, we recommend that testing for atherosclerosis or ischemia, perhaps with cardiac CT as the initial test, be reserved for those in whom medical treatment goals cannot be met and for selected individuals in whom there is strong clinical suspicion of very-high-risk CAD. Better approaches to identify such individuals based on readily obtained clinical variables are sorely needed.
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PMID:Screening for coronary artery disease in patients with diabetes. 1790 30

We investigated the effects of ischemic preconditioning (IP) on reperfusion arrhythmias in type 2 diabetic rats as well as the effects of the insulin sensitizer pioglitazone. Thirty-week-old OLETF rats with or without pioglitazone (10 mg/kgBW, orally) were used as a model for type 2 diabetes. LETO rats served as controls. The incidences and durations of reperfusion ventricular tachyarrhythmias (RVT) were evaluated using a working heart method. After 5 minutes of initial perfusion, the rats were divided into the following groups: 1) control rats without IP (CIP(-)), 2) control rats with IP (CIP(+)), 3) diabetic rats without IP (DIP(-)), 4) diabetic rats with IP (DIP(+)), 5) pioglitazone-treated diabetic rats without IP (TDIP(-)), and 6) pioglitazone-treated diabetic rats with IP (TDIP(+)). Three 2-minute cycles of global diastolic ischemia and 5 minutes of reperfusion before long ischemia were performed as IP. The incidence and duration of RVT in CIP(+) were significantly lower than in CIP(-). There was no significant difference in the duration of RVT between DIP(+) and DIP(-). However, the duration of RVT in TDIP(+) was significantly shorter than TDIP(-). These results suggested that the effects of IP on reperfusion arrhythmias are deteriorated in type 2 diabetic rats. The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats.
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PMID:The insulin sensitizer pioglitazone improves the deterioration of ischemic preconditioning in type 2 diabetes mellitus rats. 1799 72

Data of treatment of 45 patients with stable angina combined with type 2 diabetes mellitus are presented. Supplementation of standard anti-ischemic therapy with cytoprotective preparation trimetazidine MB (Preductal MB) revealed greater efficacy of treatment manifesting not only by decrease of functional class in observed patients but also by increase of volume of performed physical load, decrease of episodes of ischemia during 24 hours (according to Holter monitoring data), as well as decrease of mean duration of ischemia (painful and painless). A conclusion is made about feasibility of prescribing cytoprotective preparation trimetazidine MB while providing complex therapy to patients with stable form of ischemic heart disease.
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PMID:[Correction of episodes of transitory myocardial ischemia with trimetazidine in patients with ischemic heart disease combined with type 2 diabetes mellitus]. 1826 Aug 90

Endothelial function is widely evaluated by vasodilatation of the brachial artery induced by ischemia (flow-mediated vasodilatation, FMD). The function of the endothelium, in this setting, is to sense wall shear stress (WSS) increase and to release vasodilators. Following current guidelines FMD is measured 50-60s after ischemia. It is not known whether this lapse of time is sufficient to observe maximal vasodilatation, especially in diseased subjects. Sixty-six subjects with type 2 diabetes and 30 controls underwent FMD-test. Brachial artery WSS was measured at rest and during the first 15s after ischemia as index of peripheral resistances vessels reactivity, and FMD at 50, 120, 180, and 300s after ischemia as index of conduit vessel function. All controls exhibited increased WSS and peak FMD at 50s. Among subjects with diabetes three groups were identified based on the time at which peak FMD occurred. Twenty subjects with diabetes exhibited peak at 50s (Early FMD), 28 at 2 min (Late FMD), and 18 showed no FMD (Absent FMD). Peak FMD in Late FMD subgroup was comparable to peak in control subjects and significantly higher than peak in other subjects with diabetes. The "Absent FMD" group showed also impaired WSS. The present findings demonstrate that brachial artery response to ischemia is heterogeneous in type 2 diabetes, suggesting different mechanisms responsible for FMD alteration in this condition.
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PMID:Endothelial dysfunction or dysfunctions? Identification of three different FMD responses in males with type 2 diabetes. 1826 89

Adiponectin is a circulating cytokine with important cardioprotective effects. Plasma adiponectin levels are significantly reduced in patients with insulin resistance and type II diabetes mellitus and cardiovascular disease. Although adiponectin is primarily synthesized by adipocytes, new studies reveal that adiponectin is secreted by other cell types, including cardiomyocytes. Control of adiponectin gene expression in heart and microvasculature is poorly understood. We investigated the regulation of adiponectin expression by the transcription factor hypoxia inducible factor-1 (HIF-1) and its role in attenuating cardiac reperfusion injury. HIF-1 regulation of adiponectin was examined by isolating and characterizing the murine adiponectin promoter. HIF-1-dependent activation of the murine adiponectin promoter was verified via electrophoretic mobility shift assays, transient transfection assays, and QPCR. We show for the first time that HIF-1 activation via an siRNA-mediated prolyl 4-hydroxylase-2 gene silencing strategy induced adiponectin mRNA expression in murine microvascular endothelium in vitro (17-fold), intact hearts (22-fold, wild type; 5-fold, obese/diabetic) and white adipose tissue (37-fold, wild-type; 9.6-fold, obese/diabetic). HIF-1-induced adiponectin expression was associated with improved myocardial viability in obese/diabetic mice (32% increase) and preservation of left ventricular function (36% increase in rate pressure product). Our studies suggest that local production of adiponectin by cardiomyocytes/microvascular endothelial cells may regulate cardiac function and indicate a novel strategy for protecting diabetic hearts from ischemia/reperfusion injury.
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PMID:Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. 1828 86

Deficient repair activity for 8-hydroxy-2'-deoxyguanine (8-oxoguanine), a premutagenic oxidative DNA damage, has been observed in affected tissues in neurodegenerative diseases of aging, such as Alzheimer's disease, and in ischemia/reperfusion injury, type 2 diabetes mellitus, and cancer. These conditions have in common the accumulation of oxidative DNA damage, which is believed to play a role in disease progression, and loss of intracellular calcium regulation. These observations suggest that oxidative DNA damage repair capacity may be influenced by fluctuations in cellular calcium. We have identified human 8-oxoguanine-DNA glycosylase 1 (OGG1), the major 8-oxoguanine repair activity, as a specific target of the Ca(2+)-dependent protease Calpain I. Protein sequencing of a truncated partially calpain-digested OGG1 revealed that calpain recognizes OGG1 for degradation at a putative PEST (proline, glutamic acid, serine, threonine) sequence in the C-terminus of the enzyme. Co-immunoprecipitation experiments showed that OGG1 and Calpain I are associated in human cells. Exposure of HeLa cells to hydrogen peroxide or cisplatin resulted in the degradation of OGG1. Pretreatment of cells with the calpain inhibitor calpeptin resulted in inhibition of OGG1 proteolysis and suggests that OGG1 is a target for calpain-mediated degradation in vivo during oxidative stress- and cisplatin-induced apoptosis. Polymorphic OGG1 S326C was comparatively resistant to calpain digestion in vitro, yet was also degraded by a calpain-dependent pathway in vivo following DNA damaging agent exposure. The degradation of OGG1 by calpain may contribute to decreased 8-oxoguanine repair activity and elevated levels of 8-oxoguanine reported in tissues undergoing chronic oxidative stress, ischemia/reperfusion, and other cellular stressors known to produce perturbations of intracellular calcium homeostasis which activate calpain.
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PMID:OGG1 is degraded by calpain following oxidative stress and cisplatin exposure. 1829 29

In patients admitted to intensive care units with an acute myocardial infarction (AMI), the concomitant occurrence of hyperglycemia enhances the risk of morbidity and mortality, whether or not the patient has a prior diagnosis of diabetes. Stress hyperglycemia shares many properties with hyperglycemia associated with type 2 diabetes, including increased oxidative stress, inflammation, and activation of stress-responsive kinases. Infarcts are usually larger in patients with stress or diabetes-related hyperglycemia, and animals with type 2 diabetes sustain dramatically larger infarcts following experimental ischemia-reperfusion than do nondiabetic controls. Increased sensitivity to ischemia-reperfusion injury and more severe infarction is one reason for the poor prognosis of AMI patients with stress hyperglycemia. Evidence from clinical and preclinical studies suggests that insulin resistance and glucose homeostasis play key roles by predisposing hyperglycemic myocardial tissue to injury during ischemia and reperfusion.
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PMID:Stress hyperglycemia and enhanced sensitivity to myocardial infarction. 1836 31


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