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)

The endothelium is the first line of defense for maintaining normal vascular function in the vessel wall; however, the endothelium is sensitive to metabolic stress. In patients with insulin resistance or type 2 diabetes mellitus, a set of metabolic insults--namely high plasma levels of glucose and free fatty acids, increased inflammation, dyslipidemia, and hypertension--cause endothelial dysfunction and a transition from an antiatherogenic endothelium to a proatherogenic endothelium. Disruption of endothelial function leads to activation of platelets and macrophages, increased thrombotic potential, transition of macrophages to foam cells, stimulation of cytokine secretion, and proliferation of vascular smooth muscle cells. Insulin-sensitizing agents, such as the thiazolidinediones (TZDs), improve flow-mediated vasodilation, decrease macrophage and smooth muscle cell activation, proliferation, and migration, and decrease plaque formation. The TZDs exert multifaceted effects on the vasculature by regulating the expression of transcription factors and orchestrating whole-gene programs that restore vascular physiology to the healthy state. Exercise training and increased levels of habitual physical activity have therapeutic benefit in terms of both preventing and treating insulin resistance and diabetes. However, this benefit of exercise training and increased physical activity is complicated by the fact that individuals with insulin resistance or type 2 diabetes have decreased maximal exercise capacity or maximal oxygen consumption and have slower oxygen uptake kinetics at the beginning of exercise. Both of these abnormalities contribute to the decreased levels of habitual physical activity observed in patients with diabetes. Preliminary data suggest that TZDs improve measures of cardiac function and exercise capacity, and investigators are assessing the impact of treatment with rosiglitazone on exercise capacity in an ongoing clinical trial.
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PMID:Novel actions of thiazolidinediones on vascular function and exercise capacity. 1467 69

The vascular endothelium is an active, dynamic tissue that controls many important functions, including regulation of vascular tone and maintenance of blood circulation, fluidity, coagulation, and inflammatory responses. Cardiovascular risk factors affect many of the normal functions of the endothelium. In particular, oxidized low-density lipoprotein cholesterol initiates a series of events that begin with cell activation, endothelial dysfunction, local inflammation, and a procoagulant vascular surface. These conspire to result in plaque formation and ultimately plaque rupture and cardiovascular events. Endothelial dysfunction may be evaluated by means of invasive techniques, such as coronary artery reactivity to acetylcholine, or noninvasive techniques, such as brachial artery ultrasonography. Loss of endothelium-dependent vasodilation is a characteristic feature throughout the development of atherosclerosis, and it is independently related to future adverse cardiovascular risk. Therefore, measurement of endothelial function can possibly be used to determine risk, to triage management, and to improve outcomes. At the same time, inflammation is a crucial factor in the atherosclerotic disease process. To identify and monitor the ongoing inflammatory process, markers of inflammation such as C-reactive protein (CRP) have been studied. Scientific evidence shows that elevated plasma CRP values add to the predictive ability of other established risk factors; moreover, elevated values appear to augment the Framingham Coronary Risk Score in identifying individuals who should be considered for cardioprotective treatment programs. Interestingly, thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-gamma agonists that are effective in the treatment of type 2 diabetes mellitus, not only increase insulin sensitivity but can benefit endothelial function because they exhibit anti-inflammatory effects. For many individuals, including those with the metabolic syndrome and/or type 2 diabetes, endothelial dysfunction and elevated plasma CRP levels indicate increased risk of cardiovascular disease. Notably, the TZDs have been shown to reduce CRP levels and may improve endothelial function.
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PMID:Endothelial function, inflammation, and prognosis in cardiovascular disease. 1467 74

Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Given these similarities, we questioned whether there may be a common underlying mechanism predisposing to islet and cerebral amyloid. To address this, we first examined the prevalence of type 2 diabetes in a community-based controlled study, the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease versus control subjects without Alzheimer disease. In addition to this clinical study, we performed a pathological study of autopsy cases from this same community to determine whether there is an increased prevalence of islet amyloid in patients with Alzheimer disease and increased prevalence of cerebral amyloid in patients with type 2 diabetes. Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease control subjects n = 138) were classified according to fasting glucose concentration (FPG) as nondiabetic (FPG <110 mg/dl), impaired fasting glucose (IFG, FPG 110-125 mg/dl), and type 2 diabetes (FPG >126 mg/dl). The mean slope of FPG over 10 years in each case was also compared between Alzheimer disease and non-Alzheimer disease control subjects. Pancreas and brain were examined from autopsy specimens obtained from 105 humans (first, 28 cases of Alzheimer disease disease vs. 21 non-Alzheimer disease control subjects and, second, 35 subjects with type 2 diabetes vs. 21 non-type 2 diabetes control subjects) for the presence of islet and brain amyloid. Both type 2 diabetes (35% vs. 18%; P < 0.05) and IFG (46% vs. 24%; P < 0.01) were more prevalent in Alzheimer disease versus non-Alzheimer disease control subjects, so 81% of cases of Alzheimer disease had either type 2 diabetes or IFG. The slope of increase of FPG with age over 10 years was also greater in Alzheimer disease than non-Alzheimer disease control subjects (P < 0.01). Islet amyloid was more frequent (P < 0.05) and extensive (P < 0.05) in patients with Alzheimer disease than in non-Alzheimer disease control subjects. However, diffuse and neuritic plaques were not more common in type 2 diabetes than in control subjects. In cases of type 2 diabetes when they were present, the duration of type 2 diabetes correlated with the density of diffuse (P < 0.001) and neuritic plaques (P < 0.01). In this community cohort from southeast Minnesota, type 2 diabetes and IFG are more common in patients with Alzheimer disease than in control subjects, as is the pathological hallmark of type 2 diabetes, islet amyloid. However, there was no increase in brain plaque formation in cases of type 2 diabetes, although when it was present, it correlated in extent with duration of diabetes. These data support the hypothesis that patients with Alzheimer disease are more vulnerable to type 2 diabetes and the possibility of linkage between the processes responsible for loss of brain cells and beta-cells in these diseases.
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PMID:Increased risk of type 2 diabetes in Alzheimer disease. 1474

The aim of the present study was to identify clinical and audiologic characteristics of idiopathic sudden hearing loss (ISHL) in patients with type 2 diabetes. We retrospectively investigated 148 cases of ISHL, whose age was more than 40 years, comparing clinical and audiologic valuables between diabetic and non-diabetic patients. Twenty-four patients (16.2%) had type 2 diabetes (16 male, 8 female). Prevalence of hypertension and hyperlipidemia were significantly greater in diabetic patients. Hearing in the affected ear was more impaired in diabetic than non-diabetic patients, although hearing in the unaffected ear and degree of recovery did not differ significantly. Mean BMI, duration of diabetes, HbA1c values, and ultrasonographically determined carotid intima-media thickness (IMT) and plaque scores in diabetic patients with ISHL were 24.0+/-3.7 kg/m(2), 9.8+/-7.8 years, 7.8+/-1.5%, 0.83+/-0.16 mm, and 3.8+/-2.8, respectively. Of 17 diabetic patients whose ISHL was treated with steroids, 12 required insulin for glycemic control during treatment. Compared with diabetic patients without ISHL, HbA1c value was significantly higher in diabetic patients with ISHL (7.2+/-1.2% versus 7.8+/-1.5%, P=0.0202). In conclusion, nearly 16% of our patients with ISHL had type 2 diabetes, and this subgroup was associated with more severe hearing loss. Further studies are needed to determine which subgroups of diabetic patients are most likely to develop ISHL, which patients are predisposed to more severe hearing loss, and how various factors and treatments influence outcome.
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PMID:Idiopathic sudden hearing loss in patients with type 2 diabetes. 1475 92

Cholesterol plays an important role in atherogenesis. Cholesterol-ester that has been carried by circulating low-density lipoprotein particles accumulates in the atherosclerotic plaque. Statins are considered the most potent and effective agents for reducing low-density lipoprotein cholesterol and the incidence of cardiovascular events. Total cholesterol and LDL cholesterol levels, however, are not always a useful marker for distinguishing patients with or without cardiovascular disease. Low levels of high-density lipoprotein cholesterol are the most predictive marker for cardiovascular disease. Low HDL cholesterol levels originate in some genetic and acquired diseases and conditions. Most cases of low HDL cholesterol associated with the development of atherosclerosis are of secondary origin, especially those associated with increasing triglyceride-rich lipoprotein. These conditions are present in insulin-resistant syndrome, namely metabolic syndrome. Type 2 diabetes mellitus and the closely related metabolic syndrome are associated with a significant risk for cardiovascular disease. Recent evidence suggests that both conditions are increasing in epidemic proportions. Dyslipidemia is characterized by increased triglyceride-rich lipoproteins; low high-density lipoprotein cholesterol; small, dense low-density lipoprotein particles; and increased postprandial lipemia. All these lipoprotein disturbances accelerate atherosclerosis. It is likely that many patients will need lipid-modifying therapy to help prevent cardiovascular disease.
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PMID:[Atherosclerosis and metabolic disease]. 1502 16

Macrovascular complications present from the viewpoint of morbidity and mortality the biggest risk in type 2 diabetics. An aim of this work is to show ways of detecting clinical and preclinical phases of atherosclerosis with special regard to carotid system. In our paper we have been presenting a sample of 239 patients with cardiovascular incidents and findings on their extracranial carotid systems detected by duplex sonography. 88 patients (36.8%) in the sample had type 2 diabetes, their average age was 68.2 +/- 8.5. 35 were on a diet, 34 were treated with peroral antidiabetics, and 19 with insulin. Findings on extracranial carotid systems were normal in 27.3% of diabetics, in stenoses up to 50% was lumen in 50%, in stenoses 51-70% was lumen in 15.9%, and in stenoses 71-95% was lumen in 6.8% (compared to 3.9 in nondiabetics). Intimomedial thickness (IMT) in a group with positive microalbuminuria was 0.9 +/- 0.3 mm and in a group with negative microalbuminuria 0.87 +/- 0.18 mm. Intimomedial thickness (IMT) and microalbuminuria (MAU) are the markers of risk for atherosclerosis and enable to detect preclinical stages of atherosclerosis. Another enzyme indicated in the process of atherosclerosis is PAPP-A, an indicator of plaque instability. Early detection and early intervention of the atherosclerotic process can prevent growth of atherosclerosis, especially during epidemic increase of type 2 diabetes.
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PMID:[The carotid drainage system--a "window" into the atherosclerosis process in diabetics?]. 1504 Jan 65

Diabetes mellitus is a metabolic disease with explicit complications on coronary vascular system. The incidence of coronary disease is rising in type 1 as well as in type 2 diabetes mellitus, and it is caused by precipitating atherosclerosis. It is unquestionable that disorders of different metabolic pathways cause acute coronary syndrome, the same holding true for postinfarction complications. Strict blood glucose control (glucose value should be close to the physiologic values) is imperative not only in the prevention but also in the treatment of acute coronary syndrome and prevention of reinfarction. It is obvious that medicamentous and surgical treatment of coronary heart disease in diabetic patients can reduce morbidity and mortality. The treatment of acute coronary heart syndrome in diabetic patients is very similar to that in nondiabetic patients, however, it demands extra efforts to establish good metabolic control. Due to more than one narrowing of coronary arteries in diabetic patients, angioplasty is often less efficient and there is a need of specific evaluation by a cardio-cardio surgical team to choose the method of treatment: stent implantation or arterial bypass. The strategy of optimal revascularization for diabetic patients who have multivascular coronary heart disease is still controversial. Although data on early percutaneous or surgical revascularization show longterm benefit, the early studies were carried out before the extensive use of intracoronary stents and thrombocyte inhibitors GP IIb/IIa. A dilemma about this question showed up when excellent results of drug eluting intracoronary stents brought up credibility of compared studies. For best patient selection, it has been recommended that decision should be based more on coronary anatomy rather than the presence or absence of diabetes mellitus. Surgical revascularization (CAGB) should be considered in patients with diabetes mellitus who have stenosis of the left main coronary artery, significant diffuse stenosis involving each of epicardial vessels, and patients who have mild to significant left ventricular systolic dysfunction. Patients with a relatively focal nature of the disease and free from left main coronary artery or confluence of front left descendent artery could be considered for PCI (primary coronary intervention). When stents become widely available, patients would probably request PCI first instead of CABG. It is very important to remember that irrespective of PCI or CABG being preferred in diabetic patients, the role of drug therapy is enormous. Due to the diabetic patient susceptibility to fast progression of the disease and plaque rupture, drug therapy is indispensable in this population, e.g., aspirin, clopidogrel, 3-hydroxy-3-methylglytaryl-coenzyme A (HMGCoA) inhibitor reductase and ACE-inhibitor.
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PMID:[Acute coronary syndrome in diabetes]. 1520 3

Advanced glycation end products (AGEs) are critically involved in atherogenesis in diabetes by binding to receptors for AGE (RAGEs) in vascular cells, thus inducing the expression of proinflammatory mediators. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development. Therefore, limiting RAGE expression might be an intriguing concept to modulate vascular disease in diabetic patients. The present study investigated whether thiazolidinediones (TZDs), antidiabetic agents clinically used to treat patients with type 2 diabetes, might modulate endothelial RAGE expression. Stimulation of human endothelial cells with rosiglitazone or pioglitazone decreased basal as well as tumor necrosis factor-alpha-induced RAGE cell surface and total protein expression. In addition, TZDs reduced RAGE mRNA expression in endothelial cells. These effects on RAGE expression were caused by an inhibition of nuclear factor-kappaB (NF-kappaB) activation at the proximal NF-kappaB site of the RAGE promoter. The functional relevance of reduced RAGE expression was demonstrated by showing that pretreatment of endothelial cells with TZDs decreased AGE- as well as beta-amyloid-induced monocyte chemoattractant protein-1 expression. In conclusion, TZDs reduce RAGE expression in human endothelial cells, thus limiting the cells' susceptibility toward proinflammatory AGE effects. These data provide new insight on how TZDs, in addition to their metabolic effects, might modulate the development of vascular dysfunction in diabetic patients.
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PMID:Thiazolidinediones reduce endothelial expression of receptors for advanced glycation end products. 1544 98

The metabolic syndrome and type 2 diabetes are associated with endothelial activation (and thus with inflammatory processes leading to atherosclerosis), but the mechanisms that underlie these associations are not fully understood. Endothelial intercellular adhesion molecule (ICAM)-1 plays an important role in the recruitment of immune cells during the development of atherosclerotic plaque and is a marker of inflammatory disease. We performed bivariate quantitative genetic analyses to estimate genetic and environmental correlations between circulating ICAM-1 concentration and 17 phenotypes associated with the metabolic syndrome. Our study population comprised 428 adults in 20 extended Mexican-American families from the San Antonio Family Heart Study (SAFHS). Circulating ICAM-1 concentration is heritable (h(2) = 0.56). ICAM-1 concentration showed significant positive genetic correlations (range 0.32-0.52, P < 0.05) with fasting insulin, insulin 2 h after oral glucose challenge, homeostasis model assessment of insulin resistance, BMI, waist circumference, and leptin concentration; negative genetic correlation with HDL3 cholesterol concentration; and negative environmental correlation with adiponectin concentration. Significant genetic correlations were not found between ICAM-1 and fasting or 2-h serum glucose or systolic or diastolic blood pressure. Thus, ICAM-1 expression may share common genetic modulation with traits related to obesity, insulin resistance, and HDL3 cholesterol, but not with hyperglycemia or hypertension per se.
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PMID:Intercellular adhesion molecule-1 concentration is genetically correlated with insulin resistance, obesity, and HDL concentration in Mexican Americans. 1544 2

Patients with type 2 diabetes are at high risk of cardiovascular disease. In addition to treating hyperglycemia, the thiazolidinedione (TZD) class of antidiabetic agents may also benefit the cardiovascular complications associated with the disease. The two available TZDs, pioglitazone and rosiglitazone, are peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists that influence gene expression of key proteins involved in regulating glucose and lipid metabolism. Tumor necrosis factor-alpha (TNF-alpha) and adiponectin are believed to be important in the development of insulin resistance and atherosclerosis. Understanding the role of these cytokines in the inflammatory processes that trigger plaque development might lead to identification of other potential mechanisms that could be exploited to enhance future treatments for patients with diabetes and atherosclerosis.
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PMID:What are the effects of peroxisome proliferator-activated receptor agonists on adiponectin, tumor necrosis factor-alpha, and other cytokines in insulin resistance? 1547 Sep 6


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