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)

Type 2 diabetes is one of the major risk factors for the development of CAD and subsequent MI. Inflammation, whereby ICAM-1 plays an important role, has been implicated in the pathogenesis of MI. The K469E polymorphism of the ICAM-1 gene has recently been associated with ischemic stroke, atherosclerosis of femoral arteries and microvascular complications of type 2 diabetes. We examined the association between the K469E polymorphism of the ICAM-1 gene and MI among the patients with type 2 diabetes in Slovenian population. Genotyping of the K469E polymorphism of the ICAM-1 gene was performed for 367 subjects with type 2 diabetes: 152 patients with MI and 215 with no history of CAD. The K469E ICAM-1 genotype distribution in patients with MI (EE = 21.7 %, EK = 47.4 %, KK = 30.9 %) did not differ from genotype distribution in patients without CAD (EE = 19.1 %, EK = 50.7 %, KK = 30.2 %), and the EE genotype was not associated with MI in subjects with type 2 diabetes (P = 0.5). In conclusion, the K469E polymorphism of the ICAM-1 gene was not associated with MI in patients with type 2 diabetes, and therefore may not be used as a genetic marker for MI in patients with type 2 diabetes.
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PMID:The K469E polymorphism of the intracellular adhesion molecule 1 (ICAM-1) gene is not associated with myocardial infarction in Caucasians with type 2 diabetes. 1708 18

The exact factors contributing to the pathogenesis of type 2 diabetes remain elusive. Lately, it was suggested that inflammation and activation of the innate immune system could be linked to type 2 diabetes pathogenesis and also to the development of common diabetic complications, mainly atherosclerosis. The aim of this study was to investigate the role of monocytes in this sub-clinical inflammatory state and test 1,25-dihydroxyvitamin D(3), the active form of Vitamin D, as an anti-inflammatory agent. For this purpose, monocytes from type 2 diabetic patients were compared to monocytes from healthy controls and type 1 diabetic patients. The expression profile of inflammatory markers in freshly isolated and immune-stimulated monocytes was measured by quantitative real-time RT-PCR. Type 2 diabetic patients showed significantly higher expression levels of TNF-alpha, IL-6, IL-1, IL-8, COX-2, ICAM-1 and B7-1 compared to controls and type 1 diabetic patients. 1,25-Dihydroxyvitamin D(3) was able to down-regulate the expression of TNF-alpha, IL-6, IL-1, and IL-8, confirming its immunomodulatory properties. From these data we concluded that monocytes from type 2 diabetic patients have a pro-inflammatory profile. In addition, 1,25-dihydroxyvitamin D(3) was able to modulate inflammation in these monocytes.
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PMID:Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-Dihydroxyvitamin D(3) works as anti-inflammatory. 1711 20

The aim of the study was to investigate, whether the degree of metabolic risk factors for atherosclerotic complications in a very rare kind of obesity, the Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome (LBS), are comparable or different from "simple" truncal obesity. 10 patients with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared with 19 BMI - matched patients with "simple" truncal obesity and obstructive sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal obesity without OSAS. Markers of subclinical inflammation and thrombocyte activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein = CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin were studied. The prevalence of atherogenic risk factors as hypertension (80%), type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte activation showed an indifferent picture with lower levels of circulating IL-6 and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin and adiponectin were higher than in controls. However, the accumulation of "classic" cardiovascular risk factors in the LBS group was well reflected by the presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients, putting LBS patients - if obese - at an atherosclerotic risk at least comparable to obese persons.
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PMID:Adiponectin, resistin and subclinical inflammation--the metabolic burden in Launois Bensaude Syndrome, a rare form of obesity. 1744 28

Recent studies indicate that relaxin as well as VEGF possess cardioprotective properties. This study aimed to determine the association of relaxin with VEGF in patients with type 2 diabetes. We therefore analyzed samples from a recent study showing the benefits of anti-diabetic treatment on cardiovascular risk markers independently from glycemic control. VEGF, relaxin and markers of endothelial dysfunction, s-ICAM-1 and s-VCAM-1, were compared after 26 +/- 2 weeks of antidiabetic treatment with pioglitazone or glimepiride with their base line values. A total of 151 data sets (patients age, 62.7 +/- 8.1 years, diabetes duration, 6.8 +/- 6.6 years, 57 women, 94 men) were available for the analysis. Baseline values were in median, relaxin: 27.4 pg/mL 125% quartile 15.8; 75% quartile: 45.21, s-ICAM-1: 294 ng/mL [25% quartile: 260; 75% quartile: 331], s-VCAM-1: 677 ng/mL [25% quartile: 589; 75% quartile 871], VEGF: 350 pg/mL [25% quartile: 251; 75% quartile: 514]. Parameter variation after therapy showed a significant correlation of relaxin expression with VEGF expression (p = 0.02) in the entire study group. The correlation was seen in the subgroup of male patients (p < 0.01) but did not reach significance in the female patients (p = 0.71). No further correlation was observed analyzing the other investigated parameters. Our data suggest that relaxin may exert its cardioprotective action possibly via VEGF increase, particularly in men. In women, other pathways may superimpose this effect. In conclusion, our study supports the hypothesis of different regulating pathways and effects of relaxin in men and women also in patients with type 2 diabetes.
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PMID:Relaxin expression correlates significantly with serum changes in VEGF in response to antidiabetic treatment in male patients with type 2 diabetes mellitus. 1744 57

Metabolic syndrome is considered a hyperinsulinemic and inflammatory state closely associated to endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. The main objective of the present study was to determine whether leukocitary and soluble cell adhesion molecules were altered in patients with metabolic syndrome in comparison with control subjects. Cell adhesion molecules, mainly of leukocitary location, have been not previously evaluated in specifically designed cross-sectional studies involving male patients with metabolic syndrome. Moreover, other circulating markers of different candidate atherogenic risk parameters were also studied and the potential existence of a progressive relation between the number of metabolic syndrome components and the above mentioned biomarkers was analyzed. Thirty one male patients with metabolic syndrome (ATPIII definition) and 56 male control subjects were studied. We evaluated different markers of insulin resistance, inflammation and atherosclerosis, as well as protective factors. Patients with metabolic syndrome showed (a) hypoadiponectinemia (4551 +/- 2302 ng/ml vs. 5865 +/- 2548 ng/ml, respectively; p<0.05), (b) an atherogenic lipid and lipoprotein profile, (c) altered HDL chemical composition accompanied by higher cholesteryl ester-triglyceride interchange carried out by CETP, (d) diminished Lp-PLA(2) activity (6.5 +/- 1.9 vs. 7.3 +/- 2.2, p<0.05, respectively), antioxidant enzyme related with LDL oxidation, which was positively associated with QUICKI and negatively with VCAM-1 and lymphocyte CD18, and (e) high soluble (VCAM-1: 17 +/-5 vs. 13 +/- 4 ng/ml, respectively; p<0.0005) and leukocyte adhesion molecule expression (monocyte CD54: 52 +/- 15 vs. 45 +/-12 arbitrary units, respectively; p<0.0005; and lymphocyte CD49d: 312 +/- 56 vs. 284 +/- 64 arbitrary units, respectively; p < 0.05). The increment in leukocyte and soluble cell adhesion molecules, crucial for leukocyte interaction with the endothelium and migration into the artery wall, in combination with the other disorders described above reinforce the presence of a clinical status with high propensity to type 2 diabetes and atherosclerotic cardiovascular disease.
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PMID:Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with metabolic syndrome. 1809 67

The expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) were studied in the conjunctiva of diabetic patients with and without retinopathy. All patients underwent a complete ophthalmic examination including ocular fundus and retinal fluorescein angiography. The indirect immunoperoxidase method was performed on 15 normal conjunctivas taken during cataract surgery (group 1), on 40 eyes of 40 patients with type 2 diabetes without diabetic retinopathy (DR) (group 2) and 13 eyes of 13 patients with DR (group 3). ICAM-1 and VCAM-1 are located in epithelial cells, vascular endothelial cells and in stromal cells. Our results show a statistically significant increase in the immunohistochemical expression of these proteins in the conjunctiva of diabetic patients with and without DR in comparison with normal conjunctiva (P = 0.001). Noteworthy, ICAM-1 and VCAM-1 are upregulated in the conjunctiva of diabetic patients with and without retinopathy, reflecting the inflammatory nature of this condition and suggesting a possible role for these mediators in the pathogenesis of diabetic microangiopathy.
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PMID:Adhesion molecules (ICAM-1 and VCAM-1) and diabetic retinopathy in type 2 diabetes. 1816 14

Elevated plasma triglyceride/free fatty acid (FFA) levels and insulin resistance may promote atherosclerosis through endothelial activation (ie, increased expression of intercellular adhesion molecule 1 [ICAM-1]/vascular adhesion molecule 1 [VCAM-1], and endothelin-1 [ET-1]) in patients with the metabolic syndrome, but this has never been directly tested. The authors measured endothelial activation and insulin sensitivity (euglycemic insulin clamp with [3-(3)H]-glucose) after a 4-day low-dose lipid infusion that elevated plasma FFA to levels observed in the metabolic syndrome in 20 lean, non-diabetic insulin-resistant subjects with a strong family history of type 2 diabetes mellitus (FH(+)) and 10 insulin-sensitive volunteers without a family history of type 2 diabetes mellitus (FH(-)). Low-dose lipid infusion reduced insulin sensitivity by approximately 25% in insulin-sensitive FH(-)controls but did not worsen preexisting insulin resistance in FH(+). Low-dose lipid infusion elevated plasma ICAM and VCAM levels similarly in both groups (approximately 12%-18%; P<.01 vs baseline), while plasma ET-1 levels increased more in FH(+)vs FH(-)(46% vs 10%; P=.005). Increased plasma FFA levels closely correlated with elevated ICAM (r=0.60; P<.01), VCAM, and ET-1 levels (r=0.39 and r=0.42, respectively; P<.05). Low-dose lipid infusion induces endothelial activation in both lean insulin-resistant (FH(+)) and insulin-sensitive (FH(-)) healthy patients, regardless of changes in insulin sensitivity. These results prove that even a modest lipid oversupply may be sufficient to trigger a deleterious endothelial response.
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PMID:Chronic low-dose lipid infusion in healthy patients induces markers of endothelial activation independent of its metabolic effects. 1898 29

Hyperinsulinemia predicts future cardiovascular events, but may also contribute to atherosclerosis. We therefore studied the consequences of prolonged insulin treatment of human umbilical vein endothelial cells (HUVEC) on the phosphatidylinositol-3'-kinase(PI3K)/Akt/nitric oxide(NO)-dependent insulin signaling, together with the expression of the pro-atherogenic molecule vascular cell adhesion molecule (VCAM)-1. HUVEC were incubated with insulin (10(-11) to 10(-7) M) in short- (30 min) and long-term (24 h to 3 days) incubations. In short-term incubations, insulin did not affect constitutive Akt and eNOS at any concentration, but significantly increased their active phosphorylated forms, and NO production. In long-term incubations, however, such insulin effects on the phosphorylated forms, as well as NO production, were attenuated, promoting an effect of insulin also at concentrations otherwise ineffective. Such effects were accompanied by a boosting of insulin effect on VCAM-1 surface expression. In contrast, under similar conditions, insulin did not exert any significant effect on the surface expression of ICAM-1 and E-selectin. Therefore, prolonged exposure of HUVEC to high insulin levels induces a downregulation of the PI3K/Akt/eNOS axis. Such impairment of insulin signalling in states of prolonged hyperinsulinemia pontially contributes to detrimental effects on atherogenesis in insulin resistance states, such as the metabolic syndrome and type 2 diabetes.
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PMID:Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling. 1919 Aug 20

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are frequently used lipid-lowering drugs in type 2 diabetes. Recent emerging evidence suggests that statins protect cardiovascular function via lipid-independent mechanisms. However, the potential role of statins in diabetic retinopathy in type 2 diabetes is largely unclear. In the present study we have investigated the effect of lovastatin on blood-retinal barrier and inflammatory status in the retina of db/db mice and in cultured retinal cells. Male C57BL/KsJ db/db mice were randomly chosen to receive gastric gavage of lovastatin (10mg/kg/day) or vehicle control for 6 weeks. Retinal vascular permeability, the tight junction and inflammation were determined. The results showed that db/db mice at the age of 19 weeks exhibited significantly increased retinal vascular leakage and decreased tight junction protein level in the retina. Moreover, the expression of pro-inflammatory factors, e.g. ICAM-1 and TNF-alpha, was drastically up-regulated in diabetic retina. Lovastatin treatment normalized all of these changes. In cultured bovine retinal capillary endothelial cells (RCECs) and human ARPE-19 cells, lovastatin attenuated the decrease of tight junction protein (occludin) and adherens junction protein (VE-cadherin) expression-induced by TNF-alpha, a major pro-inflammatory cytokine in diabetic retinopathy. Lovastatin also attenuated TNF-alpha expression in RCEC. Towards the mechanism, we showed that lovastatin ameliorated ICAM-1 expression-induced by hypoxia and TNF-alpha in both RCECs and ARPE-19 cells, in part through inhibition of NF-kappaB activation. Taken together, these findings indicate that lovastatin protects blood-retinal barrier in diabetic retinopathy, which is likely via its anti-inflammatory effects.
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PMID:Systemic administration of HMG-CoA reductase inhibitor protects the blood-retinal barrier and ameliorates retinal inflammation in type 2 diabetes. 1925 13

Endothelium has long been considered both a source and a target of systemic inflammation. However, to what extent endothelial activation contributes to systemic inflammation remains unclear. This study addresses the relative contribution of endothelial activation to systemic inflammation and multiple organ dysfunction and injury (MOD/I) in an E. coli peritonitis model of sepsis. We prevented endothelial activation using transgenic (TG) mice that conditionally overexpress a mutant I-kappaBalpha, a NF-kappaB inhibitor, selectively on endothelium. TG mice and their transgene negative littermates (WT) were injected with saline or E. coli (10(8) CFU per mouse). At 7 h after E. coli infection, markers of systemic inflammation, endothelial activation, and MOD/I were assessed. WT-E. coli mice showed significantly increased serum levels of TNF-alpha, IL-1beta, IFN-gamma, IL-6, KC, and MCP-1; tissue levels of TNF-alpha, IL-6, KC, MCP-1, ICAM-1, and VCAM-1; endothelial leakage index in heart, lungs, liver, and kidney; significantly increased serum levels of AST, ALT, BUN, and creatinine; and increased mortality. Blockade of NF-kappaB-mediated endothelial activation in TG mice had no effects on serum levels of TNF-alpha, IL-1beta, IFN-gamma, IL-6, KC, and MCP-1 (markers of systemic inflammation), and tissue levels of TNF-alpha, IL-6, KC, and MCP-1, but significantly reduced tissue levels of ICAM-1 and VCAM-1 (markers of endothelial inflammation and activation) in those four organs. TG-E. coli mice displayed reversed endothelial leakage index; reduced serum levels of AST, ALT, BUN, and creatinine; and improved survival. Our data demonstrate that endothelial NF-kappaB-driven inflammatory response contributes minimally to systemic inflammation, but plays a pivotal role in septic MOD/I, suggesting that endothelium is mainly a target rather than a source of systemic inflammation.
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PMID:Selective blockade of endothelial NF-kappaB pathway differentially affects systemic inflammation and multiple organ dysfunction and injury in septic mice. 2002 May 11


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