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)

Tumor necrosis factor-alpha (TNF-alpha) level, tissue-typed plasminogen activator(t-PA) activity and PA inhibitor (PAI) activity were determined in three groups: (1) 25 NIDDM patients with silent myocardial ischemia (SMI) or silent cerebral ischemia (SCI); (2) 18NIDDM patients without SMI or SCI; (3) 20 age-matched normal controls. Diagnosis of SMI or SCI was based on the finding of ischemic evidence by SPECT of myocardiotomograph or cerebrotomograph. All patients ECG and blood pressure were normal, and they had no history of clinical symptoms and signs of MI or CI. The result showed that the TNF-alpha level and PAI activity in the ischemia group were the highest and the t-PA activity in the ischemia group was the lowest, as compared with those in the other two groups respectively. It suggests that in NIDDM patients who have high TNF-alpha, high PAI activity, low t-PA, and even no symptoms and signs of MI or CI, anticoagulant therapy might be useful to prevent the progression of diabetic macroangiopathies.
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PMID:[Changes of serum TNF-alpha level, t-PA activivty and PAI activity in patients with silent myocardial ischemia or silent cerebral ischemia]. 1068 70

Toll-like receptor-4 (TLR4), an important mediator of the innate immune response, is expressed in atherosclerotic lesions. The common single nucleotide exchange (Asp299Gly) of the TLR4 gene has been previously reported to impair TLR4 function and to be associated with a decreased risk of carotid atherosclerosis. Therefore, we aimed to detect the potential impact of TLR4 genotypes on the risk of cerebral ischemia. We studied the prevalence of two common polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) in 3 independent study populations: (1.) in a cross-sectional study including 769 patients either with type 1 or type 2 diabetes mellitus, of whom 56 (7.2%) had a history of cerebral ischemia (study 1), (2.) a case-control study (study 2) including 128 consecutive patients with cerebral ischemia, mean age 60 +/- 10.9 years and 139 control subjects, and (3.) a case-control study (study 3) including 171 young adults aged < 50 years with cerebral ischemia and 204 control individuals. In all subjects, Asp299Gly and Thr399Ile were detected by restriction length analysis. The prevalence of the TLR4 genotypes was essentially the same between patients with cerebral ischemia and control subjects in all 3 study populations. Furthermore, there was also no association with the subgroup of atherosclerotic stroke in both case-control studies populations. Although TLR4 polymorphisms are associated with a decreased risk of carotid atherosclerotic lesions, our findings indicate that they do not influence the prevalence of cerebral ischemia. This implies that the Asp299Gly TLR4-allele might have a protective role in carotid atherosclerosis, but not in cerebral ischemia.
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PMID:Lack of association between polymorphisms of the toll-like receptor 4 gene and cerebral ischemia. 1525 89

Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular disease complications, such as myocardial infarction (MI) or stroke from plaque rupture. Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in atherosclerotic plaques might lead to plaque instability and rupture caused by chronic inflammation, which up-regulates the expression of pro-inflammatory cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI site lying in the coding region at position 1267 of the HSP70-2 gene have shown that the BB genotype is associated with NIDDM. We screened 60 old NIDDM patients with carotid stenosis and 107 old healthy controls for 1267 HSP70-2 polymorphism in order to establish if an association with plaque frailty exists. Different genotypic distributions were observed between patients and healthy controls. An increased relative risk was associated with the B allele (p = 0.0107; odds ratio = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques and serum levels of triglyceride, total cholesterol and LDL cholesterol were tested from patients stratified according to their B+ (AB and BB) and B- (AA) genotypes. Plaque morphology (soft or fibrous-calcified) and the incidence of cerebral ischaemia were also assessed. B+ patients showed increased HSP70-2, IL-6, IFN-gamma, TNF-alpha and dyslipidemia as compared to B- carriers. The frequency of soft plaques increased in B+ in comparison to B- patients (67% versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in B- genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP70-2 polymorphism may be of use in identifying B+ NIDDM patients at risk for carotid plaque rupture and cerebral ischaemia.
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PMID:1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. 1599 11

Dyslipemia is a clear risk factor (RF) for ischemic heart disease and peripheral artery disease, but its relation with ischemic stroke (IS) is not so clear. HMG-CoA reductase inhibitor drugs or statins (simvastatin, atorvastatin, pravastatin) reduce the relative risk of IS by between 18 and 51% in patients with IHD, in patients with high vascular disease risk and in hypertensive patients with other RFs, acute coronary syndrome, and type 2 diabetes mellitus. According to the guidelines for use, statins are indicated in the majority of patients with IS since the risk is equivalent to that of IHD or high vascular disease risk. In view of the existing clinical evidence of benefit, it would not seem unreasonable to proceed with treatment of patients using statins while awaiting specific studies justifying their use. The non-lipid-lowering mechanisms of the statins and results of studies, such as the Heart Protection Study, provide evidence for widening the indications of statins beyond the prevention of dyslipemia, as a new therapeutic approach in the prevention of IS in patients with plasma levels of total cholesterol or low density lipoproteins currently considered within the normal distribution. The neuroprotective role, which these drugs may play in the acute phase of cerebral ischemia, remains to be clarified, but very recent evidence suggests that such patients may also benefit.
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PMID:Lipids and stroke: the opportunity of lipid-lowering treatment. 1632 54

Stress is the imbalance of homeostasis, which can be sensed even at the subcellular level. The stress-sensing capability of various organelles including the endoplasmic reticulum (ER) has been described. It has become evident that acute or prolonged ER stress plays an important role in many human diseases; especially those involving organs/tissues specialized in protein secretion. This article summarizes the emerging role of ER stress in diverse human pathophysiological conditions such as carcinogenesis and tumor progression, cerebral ischemia, plasma cell maturation and apoptosis, obesity, insulin resistance, and type 2 diabetes. Certain components of the ER stress response machinery are identified as biomarkers of the diseases or as possible targets for therapeutic intervention.
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PMID:Endoplasmic reticulum stress. 1748 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

Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.
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PMID:Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes. 2072 36

The pathogenesis of moyamoya disease remains unknown. Examination of diseases concurrent with moyamoya disease may offer a clue to clarify the pathogenesis. Coexistence of moyamoya disease, Graves' disease, and diabetes mellitus is very rare. We present the first cases in the literature. A 38-year-old man with moyamoya disease and a 43-year-old woman with quasi-moyamoya disease, both concurrent with Graves' disease and type 2 diabetes mellitus, are presented. Both patients underwent antithyroid therapy and revascularization. After normalization of thyroid hormones level and blood glucose level followed by revascularization, the symptoms of cerebral ischemia were improved. The common etiological factors of these diseases are discussed. Genetic and autoimmune factor appeared to be involved in the pathogenesis of the three diseases, which may suggest that these factors play important roles in the pathogenesis of moyamoya disease. Further studies are required to define the pathogenesis of moyamoya disease, especially in cases with comorbidities as in the present patients.
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PMID:Moyamoya disease complicated by Graves' disease and type 2 diabetes mellitus: report of two cases. 2121 11

Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension.
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PMID:[Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention]. 2122 13

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia-reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.
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PMID:Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia. 2148 12


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