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)

S100A12, also called EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) or calcium-binding protein in amniotic fluid-1, is a ligand for RAGE. It has been shown that S100A12 induces adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in the vascular endothelial cell and mediates migration and activation of monocytes/macrophages through RAGE binding and that infusion of lipopolysaccharide into mice causes time-dependent increase of S100A12 in the plasma. Therefore, circulating S100A12 protein may be involved in chronic inflammation in the atherosclerotic lesion. In this study, we developed an ELISA system that uses specific monoclonal antibodies against recombinant human S100A12 to measure plasma S100A12 levels in patients with diabetes. On using our S100A12 ELISA system, the coefficients of variation of intra- and interassay were less than 4 and 9%, respectively. The analytical lower detection limit was 0.2 ng/ml. When plasma S100A12 levels were measured by this system, the concentrations were more than twice as high in the patients with diabetes, compared with those without. Using univariate analysis in all subjects, plasma S100A12 concentrations correlated with hemoglobin A1c, fasting glucose, high-sensitivity C-reactive protein and white blood cell count. Stepwise multiple regression analyses, however, revealed that only white blood cell count and hemoglobin A1c remained significant independent determinants of plasma S100A12 concentration. These results suggest that plasma S100A12 protein levels are regulated by factors related to subclinical inflammation and glucose control in patients with type 2 diabetes.
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PMID:Increased plasma S100A12 (EN-RAGE) levels in patients with type 2 diabetes. 1553 92

Angiotensin II receptor blockade has been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes. However, the effect of angiotensin II receptor blockade on monocyte and endothelial cell adhesion markers in type 2 diabetes is poorly understood. We investigated the effects of valsartan on these markers in 53 hypertensive patients with and without type 2 diabetes mellitus. Levels of monocyte activation markers (soluble CD14: 2.1+/-0.9 vs. 3.3+/-1.4 microg/ml, p<0.01; monocyte chemotactic peptide: 392+/-94 vs. 489+/-114 pg/ml, p<0.05; and monocyte-derived microparticles: 264+/-98 vs. 511+/-128/microL, p<0.01) and endothelial cell activation markers (soluble E-selectin: 41+/-11 vs. 61+/-20 ng/ml, p<0.001; and soluble vascular cell adhesion molecule-1: 478+/-82 vs. 584+/-101 ng/ml, p<0.01) were significantly increased in hypertensive patients with type 2 diabetes compared to normotensive controls. In addition, the concentrations of adiponectin were significantly decreased in patients with type 2 diabetes (8.1+/-3.1 vs. 5.2+/-2.5 microg/ml, p<0.01). Regardless of the presence of diabetic complications, both systolic and diastolic blood pressures significantly decreased after valsartan administration (valsartan 80 mg/day for 8 weeks). Monocyte and endothelial cell activation markers were decreased significantly in patients with type 2 diabetes after valsartan treatment, but not in non-type 2 diabetic patients. In addition, valsartan alleviated hypoadiponectinemia in hypertensive patients with diabetes (before vs. after: 5.2+/-2.5 vs. 7.6+/-2.7 microg/ml, p<0.001) but did not increase adiponectin levels in the non-diabetic hypertensive group, for which the average adiponectin level was normal prior to treatment. These results suggest angiotensin II receptor blockade (valsartan) may be beneficial as an anti-atherosclerotic therapy in patients with type 2 diabetes in addition to its anti-hypertensive action.
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PMID:Effect of valsartan on monocyte/endothelial cell activation markers and adiponectin in hypertensive patients with type 2 diabetes mellitus. 1589 27

We compared the levels of plasma adiponectin, platelet activation markers (P-selectin, CD63, PAC-1, annexin V, and platelet-derived microparticles), and endothelial injury markers (soluble E-selectin and soluble vascular cell adhesion molecule-1) in 53 patients with type 2 diabetes mellitus to investigate potential contributions to diabetic vascular complications. In addition, we administered serotonin antagonist (sarpogrelate hydrochloride) to type 2 diabetes patients who had increased soluble E-selectin levels. The concentrations of platelet activation markers and endothelial injury markers in diabetic patients were significantly higher than those in normal subjects. However, levels of adiponectin were lower in type 2 diabetes patients than in control subjects. A total of 32 patients had high-soluble E-selectin levels (soluble E-selectin >or= 62 ng/ml); a subset of patients that also had significant elevation of platelet activation and endothelial injury markers compared with patients without high soluble E-selectin. In addition, both platelet-P-selectin and platelet-derived microparticle levels negatively correlated with the adiponectin level. Patients with high soluble E-selectin exhibited significant improvement of all markers after sarpogrelate hydrochloride treatment. These findings suggest that there is a link between vascular change in type 2 diabetes and activated platelets, endothelial dysfunction, and an adiponectin abnormality.
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PMID:5-HT2A receptor antagonist increases circulating adiponectin in patients with type 2 diabetes. 1609 33

1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells. 2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) was assayed by ELISA. 3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin). 4. Both resistin and ghrelin produced modest but significant increases in VCAM-1 expression (110 +/- 4 and 117 +/- 13% compared with controls, respectively; both P <or= 0.01). Ghrelin also increased ICAM-1 expression (119 +/- 17% of control; P <or= 0.01). 5. However, despite these increases in adhesion molecule expression, neither ghrelin nor resistin altered monocyte adhesion values. 6. Neither leptin nor insulin altered monocyte adhesion to endothelial cells or cell adhesion molecule expression. 7. Pathophysiologically relevant concentrations of ghrelin and resistin, within the range of concentrations exhibited by patients with anorexia nervosa or the Prader-Willi syndrome and type 2 diabetes, respectively, increase endothelial cell adhesion molecule expression, possibly contributing to increased atherosclerosis risk in such subjects.
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PMID:Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells. 1617 45

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.
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PMID:Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control. 1625 80

Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.
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PMID:Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus. 1628 96

Dyslipidemia and inflammation may promote renal disease via mechanisms of vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse data, however, are available on the relation of lipids and inflammatory biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a cross-sectional study of 732 men with type II DM enrolled in the Health Professionals' Follow-Up Study. Plasma creatinine was used to estimate GFR by the simplified Modification of Diet in Renal Disease (MDRD) equation. In men with a GFR <60 ml/min/1.73 m(2), triglycerides, non-high-density lipoprotein (HDL), apoprotein B, fibrinogen, soluble tumor necrosis factor receptor (sTNFR-2) and vascular cell adhesion molecule-1 (VCAM) were significantly higher when compared to the referent group (GFR> or =90 ml/min/1.73 m(2)). In multivariable logistic regression, those in the highest quartiles of the following biomarkers had increased odds of having a GFR <60 ml/min/1.73 m(2) when compared to those in the lowest quartiles: triglycerides (odds ratio (OR) 3.11; 95% CI, 1.52-6.36), fibrinogen (OR 5.40; 95% CI 2.14-13.65), sTNFR-2 (OR 8.34; 95% CI 3.50-19.88) and VCAM (OR 4.50; 95% CI 1.98-10.23). An inverse association was observed for HDL (OR 0.48; 95% CI 0.24-0.98). We found no association between C-reactive protein and GFR. The results were similar when creatinine clearance by Cockcroft-Gault was used to estimate kidney function. We conclude that several potentially modifiable lipid and inflammatory biomarkers are elevated in the setting of moderately decreased GFR in men with type II DM and may be the link between renal insufficiency and increased risk for cardiovascular events in this population.
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PMID:The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus. 1640 7

Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD), plasma homocysteine, serum lipids, folate, and inflammatory markers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha) were assessed after each 2-week treatment period. Folic acid supplementation significantly increased folate levels and lowered plasma homocysteine levels. Folic acid significantly improved FMD compared to placebo (5.8 +/- 4.8% vs 3.2 +/- 2.7%, p = 0.02). There were no significant effects of folic acid supplementation on lipids, NMD, or the inflammatory markers. There was no relationship between the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic acid supplementation can improve endothelial dysfunction in type 2 diabetics independent of homocysteine-lowering, but does not modulate markers of inflammation.
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PMID:Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering. 1688 40

To examine whether serum resistin concentrations are associated with metabolic or inflammatory markers in patients with type 2 diabetes mellitus, we examined serum concentrations levels and metabolic or inflammatory markers in 56 patients with type 2 diabetes mellitus and 41 healthy subjects. Serum levels of resistin, serum amyloid A, and soluble vascular cell adhesion molecule-1 were measured by enzyme-linked immunosorbent assay. Serum resistin levels were significantly elevated in diabetic patients compared with those in healthy subjects. Serum resistin concentrations did not correlate with body mass index; however, there was a significant positive correlation between resistin and soluble vascular cell adhesion molecule-1 in diabetic patients. Based on the present results, we conclude that resistin appears to be associated with vascular inflammatory markers in patients with type 2 diabetes mellitus.
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PMID:Relationship between serum resistin concentrations and inflammatory markers in patients with type 2 diabetes mellitus. 1714 42

The effect of the insulin sensitizer rosiglitazone (RSG) on biological markers of endothelial dysfunction in subjects with type 2 diabetes mellitus (T2DM) was investigated in a 12-week, multi-center, randomized, double-blind study. One hundred and thirty-six subjects aged 40-70 years, with FPG > or = 7.0 and < or = 15.0 mmol/l, previously treated with a single oral anti-diabetic agent or diet/exercise, were randomized to RSG 8 mg/day (n=65) or placebo (PBO, n=71). Results revealed that RSG significantly reduced soluble (s)E-selectin by -10.9% (P=0.004) compared with PBO, but did not significantly alter soluble vascular cell adhesion molecule-1 (+0.6%, P=NS). Compared with PBO, RSG also significantly reduced plasminogen activator inhibitor-1 (-36.9%, P<0.001), tissue plasminogen activator antigen (-22.7%, P<0.001), FPG (-2.8 mmol/l, P<0.001), fasting fructosamine (-42.0 mg/dl, P<0.001). Post-prandial AUC(0-4h) for free fatty acids (FFAs) reduced by -6.5 mg/dl*h from baseline (P=0.03), a change that positively and significantly correlated with changes in sE-selectin (r=0.22, P=0.05). The incidence of adverse events was similar in the two groups (RSG: 35.4%; PBO: 40.8%); the majority mild or moderate. These data support the hypothesis that, in patients with T2DM, rosiglitazone has beneficial effects on biological markers of endothelial dysfunction. Improvements in insulin sensitivity and decreases in FFAs may play a role in these effects.
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PMID:Effect of rosiglitazone on factors related to endothelial dysfunction in patients with type 2 diabetes mellitus. 1728 Jun 78


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