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

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Diabetic subjects show a remarkable increase in vascular complications, including myocardial infarction and strokes. The accelerated atherosclerosis in these patients is likely to be multifactorial. In this review, we focus on the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and the role of C-peptide as a mediator of lesion development. AGEs are proteins or lipids that become glycated after exposure to sugars. By engaging the RAGEs, AGEs induce the expression of proinflammatory mediators in various vascular cell types and are involved in a variety of microvascular and macrovascular complications. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development and RAGE deficiency in a RAGE(-/-)/apolipoprotein E(-/-) double knockout mouse attenuates the development of atherosclerosis in diabetes. On the other side, patients with type 2 diabetes show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize these two pathophysiological aspects and discuss on the one hand the potential role of the activated AGE-RAGE axis in diabetes-accelerated atherogenesis and on the other hand the role of C-peptide as a mediator in lesion development in patients with type 2 diabetes.
 ...
PMID:Advanced glycation end products and C-peptide-modulators in diabetic vasculopathy and atherogenesis. 1934 38

OBJECTIVE It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were compared. RESEARCH DESIGN AND METHODS Prospectively, coronary artery calcium (CAC) scoring and MSCT coronary angiography were performed in 135 asymptomatic patients (65 patients with type 1 diabetes and 70 patients with type 2 diabetes). The presence and extent of coronary atherosclerosis as well as plaque phenotype were assessed and compared between groups. RESULTS No difference was observed in average CAC score (217 +/- 530 vs. 174 +/- 361) or in the prevalence of coronary atherosclerosis (65% vs. 71%) in patients with type 1 and type 2 diabetes. However, the prevalence of obstructive atherosclerosis was higher in patients with type 2 diabetes (n = 24; 34%) compared with that in patients with type 1 diabetes (n = 11; 17%) (P = 0.02). In addition, a higher mean number of atherosclerotic and obstructive plaques was observed in patients with type 2 diabetes. In addition, the percentage of noncalcified plaques was higher in patients with type 2 (66%) versus type 1 diabetes (27%) (P < 0.001), resulting in a higher plaque burden for each CAC score compared with that in type 1 diabetic patients. CONCLUSIONS Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with type 1 and type 2 diabetes, CAD was more extensive in the latter. Also, a relatively higher proportion of noncalcified plaques was observed in patients with type 2 diabetes. These observations may be valuable in the development of targeted management strategies adapted to diabetes type.
 ...
PMID:Differences in atherosclerotic plaque burden and morphology between type 1 and 2 diabetes as assessed by multislice computed tomography. 1948 42

Type 2 diabetes mellitus (DM) is associated with a higher risk of cardiovascular disease and atherosclerotic burden. However little data exists in regards to plaque distribution and plaque composition in these patients. To assess for differences in the coronary plaques burden and composition among symptomatic patients with and without type 2 DM using multidetector computed tomography angiography (MDCTA). The 416 symptomatic patients (64% males, mean age: 61 +/- 13 years) with 61 (15%) reporting type 2 DM, who underwent contrast-enhanced MDCTA were studied. Enrolled patients had an intermediate to high pre-test probability of obstructive coronary artery disease. Multivariate analysis was used to correct for differences in age and gender. Patients with type 2 DM were more likely to have significant stenosis >or=70% in at least one coronary segments (33% in type 2 DM vs. 18% in non diabetic, P = 0.013), whereas 11% of both type 2 DM and non diabetics had stenosis of 50-70% (P = NS). Also type 2 DM patients had a higher number of coronary segments with mixed plaques compared to nondiabetic patients (1.67 +/- 2.01 vs. 1.23 +/- 1.61, P = 0.05), whereas no such differences were observed for non-calcified or calcified plaques. Nearly half (43%) of type 2 DM had coronary artery calcium scores (CACS) >or=400 vs. 29% in non diabetic patients (P = 0.03). Patients with type 2 DM tend to have atherosclerotic plaques which are more likely to be mixed in nature. Future studies need to elucidate the prognostic value of differences in plaque characteristics observed according to type 2 diabetic status.
 ...
PMID:Comparison of atherosclerotic plaque burden and composition between diabetic and non diabetic patients by non invasive CT angiography. 1963 98

Psoriasis is a disease mediated by Th1 and Th17 cytokines that has different phenotypes (plaque, guttate, pustular, and erythrodermic type). Aside from the well known psoriatic arthritis, associated disorders may occur more frequently than expected, including Crohn's disease, anxiety/depression, and metabolic syndrome. This is based on a constellation of different factors, including abdominal obesity, atherogenic dyslipidemia, hypertension, and glucose intolerance, and is a strong predictor of type 2 diabetes, cardiovascular disease, and stroke. People with moderate to severe psoriasis have more risk for cardiac disease, presumably due to the inflammatory nature of psoriasis, causing inflammatory changes in coronary arteries. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue. Since cardiovascular risk factors are higher in psoriatic patients, dermatologists treating moderate to severe psoriasis should screen for their presence, thus approaching psoriasis as a potential multisystem disorder.
 ...
PMID:Clinical aspects and comorbidities of psoriasis. 1966 31

(Full text is available at http://www.manu.edu.mk/prilozi). The study was aimed to define the risk factors for development of peripheral arterial (PAD) and carotid artery disease (CARD) among type 2 diabetic patients (T2D). The study population consisted of 30 patients diagnosed with type 2 diabetes and absent vascular disease. the mean age of the study population was 53.3 +/- 7.3 years. 60% of patients were women and 40% of them men. Patients were followed up for three years for development of peripheral and carotid artery disease. Peripheral arterial disease (PAD) was defined by ankle-brachial index < 0.9 or > 1.3. Carotid arterial disease was defined if carotid plaque or stenosis (> 50%) presented. We built a multivariable logistic regression analysis to define the factors of development of vascular disease and a multiple linear regression analysis to identify the factors associated independently with numerous values of carotid IMT and ABI. Development of PAD and CARD were registered in 43.8% of patients. Progression of carotid IMT was found in 62.5 % of pts. Progression of PAD was predicted by HDL - cholesterol and urea, systolic blood pressure and diabetes duration. Progression of carotid IMT was determinate with: BMI, weight, diastolic blood pressure and age. Our study defined risk factors that independently influence the development of PAD and CARD in pts with T2D. This data has clinical usefulness in the improvement of prevention and in optimizing the treatment of type 2 diabetic patients. Key words: peripheral arterial disease, ankle-brachial index, carotid plaque, carotid stenosis, IMT, type 2 diabetes.
 ...
PMID:Risk factors for development of peripheral and carotid artery disease among type 2 diabetic patients. 1973 32

We evaluated the characteristics of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus (DM) using single photon emission computed tomography (SPECT) and coronary computed tomographic angiography (CCTA). A total of 116 patients with DM without abnormal electrocardiographic findings or evidence of peripheral arterial disease (number of risk factors > or =2; 62 +/- 7 years, 59% men) underwent CCTA and SPECT. Of the 116 patients with DM, 88 (76%) had a normal single photon emission computed tomographic findings, and 28 (24%) had abnormal perfusion defects. Of the 116 patients, 92 (79%) had atherosclerotic plaques (2 +/- 2 segments per subject), and 20 (17%) had significant stenosis seen on CCTA. Patients with DM and normal findings on SPECT had a similar prevalence of atherosclerotic plaque (78% vs 82%), significant stenosis (15% vs 25%), severe stenosis (7% vs 7%), and calcified (40% vs 43%), mixed (49% vs 57%), and noncalcified plaques (26% vs 29%) and a high (>100) coronary artery calcium score (32% vs 29%; all p >0.05) compared to those with abnormal findings on SPECT. During the mid-term follow-up (24 +/- 4 months), 5 cardiac events occurred in patients with DM and normal findings on SPECT, only in those with occult CAD on CCTA: 1 sudden cardiac death and 4 revascularization procedures. In conclusion, a significant percentage of patients with DM and normal eletrocardiographic findings, no peripheral arterial disease, and normal findings on SPECT have evidence of occult CAD on CCTA. Furthermore, a small percentage had had a cardiac event by mid-term follow-up. SPECT showed limited capability to differentiate the coronary risks between patients with DM and no coronary plaque and from those with a certain degree of disease; 2 circumstances that represent different coronary risks.
 ...
PMID:Assessment of subclinical coronary atherosclerosis in asymptomatic patients with type 2 diabetes mellitus with single photon emission computed tomography and coronary computed tomography angiography. 1976 52

Obesity, particularly abdominal adiposity, is increasingly recognized as a cause of elevated cardiometabolic risk--the risk of developing type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). The predominate mechanisms appear to involve the promotion of insulin resistance, driven largely by excess free fatty acids secreted by an expanded adipose tissue mass, and the development of an inflammatory milieu due to increased secretion of inflammatory cytokines and adipokines from adipose tissue. Key proinflammatory cytokines secreted by adipocytes include tumor necrosis factor-alpha, interleukin-6, leptin, resistin, and plasminogen activator inhibitor-1. All have been variously associated with hyperinsulemia, hyperglycemia, insulin resistance, diabetes, and endothelial dysfunction, as well as plaque development, progression, and rupture. Adiponectin, another important adipocyte, has protective cardiometabolic actions; however, adiponectin levels decline with increasing obesity. Understanding the role of obesity in the pathogenesis of cardiometabolic risk is crucial for the development of treatment strategies that will provide maximum benefit for patients with, or at risk for, type 2 DM and CVD.
 ...
PMID:Overweight and obesity: the pathogenesis of cardiometabolic risk. 1978 62

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08x10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases.
 ...
PMID:Genetic determinants of circulating sphingolipid concentrations in European populations. 1979 45

Urotensin II (U-II) and its receptor G-protein-coupled receptor GPR14 (UT) exert a broad spectrum of biological functions such as vascular remodeling and vasoactive cardiac inotropic. Now some preclinical and clinical studies showing that they may play an important role in insulin resistance. Then to research the role of U-II and UT in the vascular complication of type 2 diabetes especially in the big artery, we chose the GK rat who is the diabete-2 naturally. Through the HE stain and red oil O stain to chose the artery specimens that have no Atheromatous plaque, no Fatty streak and no Fibrous plaque. The immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) to determine the degree of the expression and location of U-II and UT in the aorta. We found that U-II was significant up-regulated in the endothelial cell and adventitia of GK rat compared with healthy controls on both protein and mRNA levels. The UT was only highly enhanced in the endothelial. In the adventitia there is no difference on the quantity between two of them, These results suggest that the U-II and UT play an important role in the diabetic angiopathy especially in the large artery and maybe imply a new way to prevent the injury of artery in the diabete-2 patient.
 ...
PMID:Elevated expression of urotensin II and its receptor in great artery of type 2 diabetes and its significance. 1990 7

Anemia is a common but often overlooked complication of diabetes. We investigated the relationship between hemoglobin concentration and various factors as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Hemoglobin concentration was measured in 319 men with type 2 diabetes mellitus. We evaluated the relationship between hemoglobin concentration and various factors including age, body mass index, and glycemic control, as well as between hemoglobin concentration and pulse wave velocity or ankle-brachial index (n = 209) and between hemoglobin concentration and carotid intima-media thickness or plaque score (n = 125). Mean hemoglobin concentration was 14.2 +/- 0.80 g/dL. Body mass index (r = 0.340, P < .0001) and estimated glomerular filtration rate (r = 0.219, P = .0011) were positively associated with hemoglobin concentration, whereas age (r = -0.388, P < .0001), glycated albumin (r = -0.148, P = .0121), serum creatinine concentration (r = -0.206, P = .0019), and log (urinary albumin excretion) (r = -0.188, P = .0010) were negatively associated with hemoglobin concentration. Multiple regression analysis identified age (beta = -0.222, P = .0019), body mass index (beta = 0.145, P = .0432), systolic blood pressure (beta = 0.214, P = .0015), total cholesterol concentration (beta = 0.170, P = .0077), and serum creatinine concentration (beta = -0.181, P = .0045) as independent determinants of hemoglobin concentration. No significant association was observed between hemoglobin concentration and serum erythropoietin concentration (r = -0.079, P = .2980). Negative correlations were found between hemoglobin concentration and pulse wave velocity (r = -0.289, P < .0001) and between hemoglobin concentration and plaque score (r = -0.275, P = .0024). In conclusion, hemoglobin concentration was associated with various factors; and decreased hemoglobin concentration was associated with subclinical markers of atherosclerosis in men with type 2 diabetes mellitus.
 ...
PMID:Hemoglobin concentration in men with type 2 diabetes mellitus. 2000 24


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