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)

To evaluate whether or not activated coagulation is present in the preclinical phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree relatives of type 2 diabetic patients and 21 matched controls with no family history of diabetes. We determined the plasma levels of prothrombin fragment 1 + 2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight-1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l-1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher in relatives, without significant differences in the other haemostatic variables. Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post-infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no significant differences in insulin sensitivity. Fifteen relatives were glucose-intolerant and had lower beta-cell function and insulin sensitivity than glucose-tolerant relatives. Both subsets of relatives exhibited higher levels of prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree relatives of type 2 diabetic patients present an activated coagulation, even in the absence of minor degrees of glucose intolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabetes.
 ...
PMID:Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic patients. 887 Aug 13

We observed the changes of parameters of coagulation and fibrinolytic system in order to understand the clinical implication of these variations in type II diabetic patients. Subjects consisted of 22 patients with type II diabetes mellitus and 25 healthy controls. Compared with the control, activated partial thromboplastin time, prothrombin time were shortened in the patients. The diabetic subjects also displayed higher levels of D-dimer, serum fibrin degradation products, median concentrations of fibrinogen (3.99 vs 2.96 g/L, P < 0.01) and von Willebrand factor (149% vs 87%, P < 0.01). Levels of antithrombin III activity or antigen were not different from control values. Simple linear regression analysis revealed a negative correlation between antithrombin III activity and fast blood glucose. Diabetic patients with vascular complications had significantly higher levels of fibrinogen and D-dimer than those without diabetic angiopathy. Our data demonstrated that patients with type II diabetes mellitus had a hypercoagulable state. We believed the activation of coagulation might contribute to the vascular complications in diabetics.
 ...
PMID:Variations and clinical significance of coagulation and fibrinolysis parameters in patients with diabetes mellitus. 1080 53

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.
 ...
PMID:Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes. 1102 Apr 68

In patients with type 2 diabetes, fibrinolysis is considered impaired by increased plasma concentrations of plasminogen activator inhibitor (PAI)-1. However, several investigators found both coagulation and fibrinolysis to be activated in these patients. We further characterized the balance between coagulation and fibrinolysis in lean and obese patients with type 2 diabetes. We studied 112 type 2 diabetic patients (66 lean, 46 obese) and 69 age-matched healthy subjects (46 lean, 23 obese). We measured plasma concentrations of fibrinogen and prothrombin F1+2 (F1+2) as indicating coagulation activity and plasmin-antiplasmin complex (PAP) and D dimer as indicating fibrinolytic activity. Plasma PAI-1 concentrations also were determined. Plasma concentrations of F1+2, PAP, D dimer, and PAI-1 were higher in diabetic patients than in control subjects. Plasma fibrinogen and F1+2 were similar between lean and obese diabetic patients, but plasma PAP and D dimer were significantly lower in obese than lean diabetic patients (P <.0001, P =.0194, respectively). By multivariate analysis, plasma PAI-1 and body mass index (BMI) were independent factors in diabetic patients predicting PAP, while BMI and glycosylated hemoglobin (HbA(1c)) independently predicted D dimer. Plasma PAI-1 concentrations were significantly higher in obese than lean diabetic patients (P <.0001). In conclusions, both coagulation and fibrinolytic systems are enhanced in lean and obese type 2 diabetic patients compared with healthy subjects. Although the degree of activation of coagulation was similar between lean and obese diabetic patients, the fibrinolytic activity was lower in obese than lean patients. Fibrinolytic compensation for hypercoagulation is incomplete in obese patients with type 2 diabetes, partly because of elevated PAI-1 in the blood.
 ...
PMID:Impaired fibrinolytic compensation for hypercoagulability in obese patients with type 2 diabetes: association with increased plasminogen activator inhibitor-1. 1191 56

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin-stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 +/- 0.06 in patients with complications and 0.05 +/- 0.06 patients without complications (P =.004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 +/- 0.29 in patients with complications and 0.21 +/- 0.18 in patients without complications (P =.003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/10(6) PBMCs) was 18.4 +/- 13.2 in patients with complications and 6.96 +/- 5.2 in patients without complications (P =.003). It increased 3-fold in both groups after stimulation (P =.001). TF antigen (pg/10(6) PBMCs) was 33.7 +/- 28.6 in patients with complications, 10.4 +/- 7.8 in patients without complications (P =.02). Stimulation tripled TF antigen in both groups of patients (P =.001). The RAGE/TF axis is up-regulated in T2D patients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.
 ...
PMID:Increased expression of tissue factor and receptor for advanced glycation end products in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus with vascular complications. 1520 87

Hypercoagulation often occurs in type 2 diabetes, suggesting pleiotropy of the genes that influence disease liability and hemostasis-related phenotypes. To better understand the relationship between hemostasis and diabetes, we first used maximum-likelihood methods to estimate the relative contribution of additive genetic, measured environmental, and shared household effects to the normal variance of 16 hemostasis-related traits in 813 individuals participating in the San Antonio Family Heart Study. We estimated moderate to high heritabilities (0.20-0.60) for each phenotype. Von Willebrand factor (VWF), thrombin activatable fibrinolysis inhibitor, activated protein C (APC) ratio, factor V, and prothrombin time had heritabilities greater than 0.50. The correlation between type 2 diabetes status and the hemostasis-related traits was then partitioned into genetic and environmental components using bivariate variance-components methods. Significant (p < or = 0.05) positive genetic correlations (0.37-0.51) occurred with factors II and VIII, VWF, total protein S (tPS), and tissue factor pathway inhibitor. Significant negative genetic correlations were estimated for activated partial thromboplastin time (-0.49) and APC ratio (-0.38). By contrast, significant environmental correlations occurred only with factor II (-0.40) and tPS (-0.31). Our results suggest that genes are important contributors to the normal variation in hemostasis-related traits and that genes influencing hemostasis-related traits pleiotropically influence diabetes risk.
 ...
PMID:Heritability of hemostasis phenotypes and their correlation with type 2 diabetes status in Mexican Americans. 1611 12

The association of the single nucleotide polymorphisms (SNPs) G1691A in coagulation factor V (FV)-Leiden and G20210A in prothrombin (PRT) genes with type 2 diabetes mellitus (T2DM) were analyzed in 112 T2DM patients (58 males, 54 females; mean age 55.24 +/- 13.5 years) and 249 healthy control subjects (118 males, 131 females; mean age 53.03 +/- 13.8 years). No association was found for FV-Leiden with T2DM, as the frequency of the G/G (82.1% vs. 85.5%), G/A (17.0% vs. 14.1%), and A/A (0.9% vs. 0.4%) genotypes was not different between patients and controls, respectively (P = 0.644). Similarly, lack of association of PRT G20210A with T2DM was seen among the population studied, and the frequency of the G/G (92.9% vs. 97.2%), G/A (6.3% vs. 2.8%), and A/A (0.9% vs. 0.0%) genotypes was similar among patients and controls, respectively (P = 0.094). Neither FV-Leiden nor PRT G20210A was associated with, and no evidence for interactions between these mutations was seen in, T2DM.
 ...
PMID:Factor V G1691A (Leiden) and prothrombin G20210A single-nucleotide polymorphisms in type 2 diabetes mellitus. 1613 47

Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor.
 ...
PMID:Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. 1638 Apr 94

Tissue factor (TF) plays a pivotal role in thrombus formation. Statins and angiotensin converting enzyme inhibitors attenuate expression of TF by distinct mechanism. Therefore, we hypothesized that combined therapy with simvastatin and ramipril may have additive beneficial anti-atherogenic effects to lower TF activity when compared with either drug alone. This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each treatment period. Simvastatin and ramipril monotherapy tended to reduce TF activity (0.53 to 0.46 nM, P=0.056; 0.54 to 0.50 nM, P=0.167, respectively) while combined therapy had a significant effect (0.64 to 0.43 nM, P<0.001). All three therapies significantly reduced prothrombin fragment 1+2 (F1+2) levels from their respective baselines (P=0.037, P<0.001, and P=0.057, respectively). Combined therapy significantly reduced TF activity and F1+2 levels to a greater extent than either simvastatin or ramipril alone (P=0.029 and P=0.040 by ANOVA, respectively). Percent changes in TF activity and percent changes in F1+2 levels were significantly correlated. All three therapies reduced CD40 ligand levels from their respective baselines (P=0.098, P<0.001, and P=0.002, respectively) with no significant differences among these three therapies (P=0.204 by ANOVA). Ramipril combined with simvastatin significantly reduces plasma TF activity and F1+2 levels to a greater extent than monotherapy with either drug in patients with type 2 diabetes.
 ...
PMID:Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. 1696 76

Clinical and epidemiologic observations have led to the concept of a procoagulant state in type 2 diabetes. This study aimed to determine the coagulation status in type 2 diabetic patients using rotation thromboelastography (ROTEM), which measures the interactive dynamic coagulation process. For this purpose, 51 (30 women, 21 men) type 2 diabetic patients (mean age, 56.1 years) and 40 age-matched, sex-matched and body-mass-index-matched healthy individuals were enrolled. Twenty-seven of the diabetic group had diabetic vascular complications. ROTEM using different activators for the intrinsic and extrinsic systems of coagulation cascade (intrinsic TEM-INTEM, extrinsic TEM-EXTEM, FIBTEM) was used to measure the coagulation time (CT), clot formation time (CFT), alpha angle (alpha) and maximum clot firmness (MCF). No significant difference was found in the prothrombin time, partial thromboplastin time, thrombin time, fibrinogen and platelet count between the two groups. INTEM-CT and INTEM-CFT and EXTEM-MCF were significantly higher in the diabetic group compared with controls (P = 0.012, P = 0.007 and P = 0.029, respectively). INTEM alpha in the diabetic group was significantly lower than the controls (P = 0.001). All other parameters, including INTEM-MCF, EXTEM-CT, EXTEM-CFT, EXTEM-alpha, FIBTEM-CT, FIBTEM-CFT, FIBTEM-MCF and FIBTEM-alpha, were similar between the two groups. Taking into account these data, we conclude that there is subtle activation of the extrinsic pathway with a concomitant decrement in the intrinsic pathway of the coagulation cascade in type 2 diabetes. The exact underlying mechanisms leading to these changes, and their consequences with regard to diabetic complications, remain to be determined.
 ...
PMID:Global assessment of the coagulation status in type 2 diabetes mellitus using rotation thromboelastography. 1698 49


1 2 3 Next >>