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)

A reduced availability of nitric oxide (NO) is an important feature of endothelial dysfunction occurring early in the course of type 2 diabetes. The measurement of flow-mediated dilation (FMD) of the brachial artery after forearm ischemia is supposed to be a non-invasive method to assess endothelial production and release of NO. The impairment of reactive hyperemia due to microvascular dysfunction in diabetes might cause an insufficient increase in shear stress stimulating the endothelial NO release, thus leading to an underestimation of FMD. Therefore, the aim of the present study was to investigate the relationship between microcirculatory disturbances and the impairment of FMD in type 2 diabetic patients. 63 type 2 diabetic patients and 44 non-diabetic control subjects were investigated. Capillary blood cell velocity (CBV) was assessed at the dorsal middle phalangeal area of the left ring finger. Lumen diameter of the brachial artery was measured by high-resolution ultrasound. Patients were investigated at rest and after 5-min suprasystolic arterial compression. Percentage change of CBV during reactive hyperemia (CBV%) and flow-mediated dilation (FMD%) of the brachial artery relative to the baseline measurement were calculated. CBV% (63.4+/-10.7% vs. 124.0+/-18.5%; p<0.01) and FMD% (3.8+/-0.8% vs. 6.9+/-0.9%; p<0.01) were reduced in the diabetic patients compared to their control subjects. FMD% was not related to CBV% (r=0.14; p=0.139). The lack of an association between the reduction of endothelium-dependent vasodilation of the brachial artery and the impairment of postocclusive microvascular hyperemia observed in the present study contradicts the assumption that a reduced FMD is only the consequence of an impaired reactive hyperemia due to microvascular dysfunction. It also lends support to the suggestion that endothelial dysfunction in conduit vessels and impaired cutaneous microvascular responses to reactive hyperemia might at least partly develop independently due to several differences in their pathogenesis.
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PMID:Impaired flow-mediated vasodilation in type 2 diabetes: lack of relation to microvascular dysfunction. 1844 31

Nonalcoholic fatty liver disease (NAFLD), the most common cause of steatosis, is associated with visceral obesity and insulin resistance. With more severe risk factors (obesity, type 2 diabetes [T2D], metabolic syndrome), steatosis may be complicated by hepatocellular injury and liver inflammation (steatohepatitis or NASH). NASH can lead to perisinusoidal fibrosis and cirrhosis. Fat-laden hepatocytes are swollen, and in steatohepatitis, further swelling occurs due to hydropic change (ballooning) of hepatocytes to cause sinusoidal distortion, as visualized by in vivo microscopy, reducing intrasinusoidal volume and microvascular blood flow. Involvement of other cell types (sinusoidal endothelial cells, Kupffer cells, stellate cells) and recruitment of inflammatory cells and platelets lead to dysregulation of microvascular blood flow. In animal models, the net effect of such changes is a marked reduction of sinusoidal space (approximately 50% of control), and a decrease in the number of normally perfused sinusoids. Such microvascular damage could accentuate further liver injury and disease progression in NASH. The fatty liver is also exquisitely sensitive to ischemia-reperfusion injury, at least partly due to the propensity of unsaturated fatty acids to undergo lipid peroxidation in the face of reactive oxygen species (ROS). This has important clinical consequences, particularly limiting the use of fatty donor livers for transplantation. In this review, we discuss available data about the effects of steatosis and steatohepatitis on the hepatic microvascular structure and sinusoidal blood flow, highlighting areas for future investigation.
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PMID:Hepatic microcirculation in fatty liver disease. 1848 15

Hypertension and type 2 diabetes mellitus (T2DM) cause endothelial dysfunction probably through increased oxidant stress. Paraoxonase (PON1) is an high-density lipoprotein (HDL)-linked anti-oxidant enzyme whose capacity is influenced by a genetic polymorphism at codon 192. In the present study we have investigated the role of PON1 polymorphism on endothelial function in subjects with T2DM with or without hypertension. Three groups of male subjects were enrolled: 65 healthy control subjects without T2DM or hypertension (CON), 51 with only T2DM (DM), and 67 with both hypertension and T2DM (HYP+DM). The PON1 Gln192Arg polymorphism was determined by polymerase chain reaction (PCR) amplification and restriction analysis. Endothelial function was evaluated as flow-mediated vasodilatation (FMD) of the brachial artery after forearm ischemia. Data were analyzed according to the presence or absence of the Arg allele. Subjects with T2DM had markedly impaired FMD, compared with those of the CON group. In the CON and HYP+DM groups no difference was observed in FMD between subjects homozygous for the Gln allele and those carrying the Arg allele. In the DM group FMD was lower among those carrying the Arg allele compared with Gln/Gln homozygotes (2.1+/-2.4% vs. 6.2+/-5.2%, p=0.002). In conclusion, the present findings demonstrated that FMD was less impaired in normotensive diabetic subjects homozygous for the Gln allele, consistent with the notion that this isoform has a more effective antioxidant action that serves to protect circulating low-density lipoprotein (LDL). Hypertension seems to abolish the protective effect of the Gln isoform. These findings, however, warrant further investigation to clarify their clinical import.
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PMID:The influence of PON1 192 polymorphism on endothelial function in diabetic subjects with or without hypertension. 1849 71

The peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a regulator of anti-inflammatory genes. One of its agonists, rosiglitazone-widely used in the treatment of type 2 diabetes mellitus-has recently been reported to increase the risk for myocardial infarction. In contrast, various studies provide evidence for a rosiglitazone-induced cardioprotection in different models of acute myocardial I/R. Here, we report that this protection can still be observed after 28 days of reperfusion in a murine model even when treatment commenced after the period of ischemia (reperfusion therapy). In vitro, cells from the rat cardiomyoblast cell line H9c2(2-1) are protected against oxidative stress by incubation with rosiglitazone, which can be abrogated by dexamethasone or cycloheximide. The antioxidant enzyme heme oxygenase 1 is up-regulated in these cells after rosiglitazone treatment. Our data provide further evidence that rosiglitazone exerts protective effects during myocardial I/R and might contribute to the reevaluation of the approved drug rosiglitazone.
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PMID:Rosiglitazone is cardioprotective in a murine model of myocardial I/R. 1856 25

Diminished levels of L-arginine and endothelial nitric oxide synthase (eNOS) uncoupling through deficiency of tetrahydrobiopterin (BH(4)) may contribute to endothelial dysfunction. We investigated the effect of L-arginine and BH(4) administration on ischemia-reperfusion (I/R)-induced endothelial dysfunction in patients with type 2 diabetes and coronary artery disease (CAD). Forearm blood flow was measured by venous occlusion plethysmography in 12 patients with type 2 diabetes or impaired glucose tolerance and CAD. Forearm ischemia was induced for 20 min, followed by 60 min of reperfusion. The patients received a 15 min intra-brachial infusion of L-arginine (20 mg/min) and BH(4) (500 microg/min) or 0.9% saline starting at 15 min of ischemia on two separate study occasions. Compared with pre-ischemia the endothelium-dependent vasodilatation (EDV) induced by acetylcholine was significantly reduced at 15 and 30 min of reperfusion when saline was infused (P<0.001), but not following L-arginine and BH(4) infusion. EDV was also significantly less reduced at 15 and 30 min of reperfusion following L-arginine and BH(4) infusion, compared to saline infusion (P<0.02). Endothelium-independent vasodilatation (EIDV) induced by nitroprusside was unaffected by I/R. Venous total biopterin levels in the infused arm increased from 37+/-7 at baseline to 6644+/-1240 nmol/l during infusion of L-arginine and BH(4) (P<0.0001), whereas there was no difference in biopterin levels during saline infusion. In conclusion L-arginine and BH(4) supplementation reduces I/R-induced endothelial dysfunction, a finding which may represent a novel treatment strategy to limit I/R injury in patients with type 2 diabetes and CAD.
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PMID:L-arginine and tetrahydrobiopterin protects against ischemia/reperfusion-induced endothelial dysfunction in patients with type 2 diabetes mellitus and coronary artery disease. 1884 28

Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. When diabetes exists in patients with established CAD, absolute risk for future events is very high. Diabetic patients often have severe, yet asymptomatic, CAD. Although high-sensitivity C-reactive protein (hsCRP) is a strong independent risk factor for cardiovascular events, there is an unclear association between it and silent myocardial ischemia in diabetic patients. In this study, we assess the relationship between hsCRP and silent myocardial ischemia in Chinese with type 2 diabetes mellitus. We designed a cross-sectional study with 225 asymptomatic diabetic patients having no known CAD. Ischemia was assessed by myocardial perfusion imaging. A total of 109 patients (48.4%) was found to have silent myocardial ischemia. Logistic regression analysis revealed age (odds ratio = 4.01, P = .002) (95% confidence interval, 1.98-7.44) and hsCRP (odds ratio = 2.58, P = .005) (95% confidence interval, 1.33-5.01) to be associated with greater risk of silent myocardial ischemia. Using the American Diabetes Association screening guidelines to evaluate risk, we found silent myocardial ischemia to be equally distributed between diabetic patients with 2 or more cardiac risk factors and those with less than 2 risk factors. Twenty-seven (24.8%) patients with silent myocardial ischemia were missed when the American Diabetes Association guidelines were used alone. High-sensitivity C-reactive protein was associated with silent myocardial ischemia in our study. High-sensitivity C-reactive protein might help detect silent myocardial ischemia in diabetic Chinese who may need aggressive treatment to reduce future CAD morbidity and mortality in Taiwan.
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PMID:High-sensitivity C-reactive protein and silent myocardial ischemia in Chinese with type 2 diabetes mellitus. 1894 Mar 90

Cardiovascular disease is a major health problem in all over the world. The prevalence of type 2 diabetes mellitus has been rapidly increasing, together with the risk for cardiovascular events. Patients with diabetes, and/or with insulin resistance as well, have an impaired myocardial metabolism of glucose and free fatty acids (FFA) and accelerated and diffuse atherogenesis, with involvement of peripheral coronary segments. Significant metabolic alterations in diabetic patients are the decreased utilization of glucose and the increase in muscular and myocardial FFA uptake and oxidation, occurring as a consequence of the mismatch between blood supply and cardiac metabolic requirements. These metabolic changes are responsible both for the increased susceptibility of the diabetic heart to myocardial ischemia and for a greater decrease of myocardial performance for a given amount of ischemia, compared to non diabetic hearts. A therapeutic approach aimed at an improvement of cardiac metabolism, through manipulations of the utilization of metabolic substrates, may improve myocardial ischemia and left ventricular function. Modulation of myocardial FFA metabolism, in addition to optimal medical therapy, should be the key target for metabolic interventions in patients with coronary artery disease and diabetes. In diabetic patients the effects of modulation of FFA metabolism should be even greater than those observed in patients without diabetes.
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PMID:Optimization of cardiac metabolism in diabetes mellitus. 1899 71

Hepatic portal venous gas is most often associated with extensive bowel necrosis due to mesenteric infarction. Mortality exceeds 75% with this condition. The most common precipitating factors include ischemia, intra-abdominal abscesses and inflammatory bowel disease. In this report, we present a 75-year-old woman with extensive hepatic portal and mesenteric venous gas due to colonic diverticulitis. She had a 10-year history of type II diabetes mellitus and hypertension. She was treated by sigmoid resection and Hartmann's procedure and discharged from the hospital without any complications.
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PMID:Extensive hepatic-portal and mesenteric venous gas due to sigmoid diverticulitis. 1923 52

Cardiovascular disease is a major health problem all over the world. The prevalence of type 2 diabetes mellitus has been rapidly increasing, together with the risk of cardiovascular events. Patients with diabetes, and/or with insulin resistance as well, have an impaired myocardial metabolism of glucose and free fatty acids (FFA) and accelerated and diffuse atherogenesis, with involvement of coronary artery tree. Significant metabolic alterations at heart level in diabetic patients are the decreased utilization of glucose and the increase in muscular and myocardial FFA uptake and oxidation, occurring as a consequence of the mismatch between blood supply and cardiac metabolic requirements. These metabolic changes are responsible both for the increased susceptibility of the diabetic heart to myocardial ischemia and for a greater decrease of myocardial performance for a given amount of ischemia, compared to non diabetic hearts. A therapeutic approach aimed at an improvement of cardiac metabolism, through manipulations of the utilization of metabolic substrates, may improve myocardial ischemia and left ventricular function. Modulation of myocardial FFA metabolism, in addition to optimal medical therapy, should be the key target for metabolic interventions in patients with coronary artery disease and diabetes. In diabetic patients with ischemic heart disease, the effects of modulation of FFA metabolism could even give greater benefit than in nondiabetic patients.
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PMID:Energy metabolism in the normal and in the diabetic heart. 1927 47

Type 2 diabetes is associated with insulin resistance, endothelial dysfunction and accelerated atherosclerotic diseases. Though underlying mechanisms remain to be unraveled, p38 mitogen-activated protein kinase (MAPK) appears to play important roles in their pathogenesis. As a member of the MAPK family, it regulates the activities of many transcription factors and proteins/enzymes and thus has a wide-spectrum of biological effects. Patients with insulin resistance and/or type 2 diabetes have high levels of plasma free fatty acids, inflammatory cytokines, and/or glucose, and over-activation of the cardiovascular renin-angiotensin system, all are capable of activating p38 MAPK. p38 MAPK plays a central role in hepatic glucose and lipid metabolism, leading to increased hepatic glucose production and decreased hepatic lipogenesis. The roles of p38 MAPK in insulin-mediated glucose uptake in skeletal muscle and adipose tissue remain controversial. p38 MAPK also mediates inflammatory processes and cell apoptosis. Recent evidence suggests that p38 MAPK may be the key node linking cardiovascular insulin resistance, endothelial dysfunction and the pathogenesis of atherosclerotic diseases through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells in type 2 diabetes. In addition, p38 MAPK also contributes significantly to cardiac injury during ischemia-reperfusion.
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PMID:p38 mitogen-activated protein kinase: a critical node linking insulin resistance and cardiovascular diseases in type 2 diabetes mellitus. 1927 80


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