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)

The purpose of this study was to examine the associations of carotid artery intima-media wall thickness (IMT) with hemostatic proteins and cardiovascular risk factors (CVRFs) in participants with and without non-insulin dependent diabetes mellitus (NIDDM). IMT measurements were determined by high resolution B-mode ultrasound imaging of the carotid arteries in 921 participants with NIDDM and 11,964 non-diabetic participants aged 45-64 years. Fasting glucose, serum lipids and activated partial thromboplastin time, factor VIII fibrinogen, factor VII, antithrombin III, protein C, and von Willebrand factor measurements were made. Compared to non-diabetic participants, participants with NIDDM had a more adverse pattern of CVRFs and a more procoagulatory profile. Participants with NIDDM had 0.06 mm (8.1%) higher mean IMT compared to non-diabetic participants after adjusting for age and gender (P < 0.001). However, only plasma fibrinogen concentrations showed statistically significant positive associations with IMT in both groups. After adjusting for CVRFs and fibrinogen, mean IMT remained 0.04 mm (5.4%) higher in diabetic compared to non-diabetic participants. Despite the more procoagulatory profile in participants with NIDDM, only plasma fibrinogen concentrations were independently associated with mean IMT. The association of NIDDM with mean IMT was only partly explained by CVRFs.
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PMID:Haemostasis and carotid artery wall thickness in non-insulin dependent diabetes mellitus. 1066 Feb 18

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.
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PMID:Variations and clinical significance of coagulation and fibrinolysis parameters in patients with diabetes mellitus. 1080 53

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.
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PMID:Heritability of hemostasis phenotypes and their correlation with type 2 diabetes status in Mexican Americans. 1611 12

There is a considerable body of evidence supporting an association between hypertriglyceridaemia, a hypercoagulable state and atherothrombosis. A disorder of triglyceride metabolism is a key feature of the metabolic syndrome that increases risk of both ischaemic heart disease and type 2 diabetes approximately 3-fold. An increasing prevalence of obesity and metabolic syndrome is likely to contribute markedly to the prevalent ischaemic heart in the foreseeable future, and therefore it is crucial to understand mechanisms linking hypertriglyceridaemia and a hypercoagulable state. Activation of platelets and the coagulation cascade are intertwined. VLDL and remnant lipoprotein concentrations are often increased with the metabolic syndrome. These lipoproteins have the capacity to activate platelets and the coagulation pathway, and to support the assembly of the prothrombinase complex. VLDL also upregulates expression of the plasminogen activator inhibitor-1 gene and plasminogen activator inhibitor-1 antigen and activity, a process accompanied by platelet aggregation and clot formation. The surface membrane of activated platelets also supports the assembly and activity of the prothrombinase complex, resulting in further thrombin generation and amplification of the coagulation cascade. Fibrinolysis is also less efficient when thrombin is generated. Thrombin induces thrombin activatable fibrinolysis inhibitor. Thrombin activatable fibrinolysis inhibitor is a carboxypeptidase that cleaves the carboxylic lysine residues on fibrin, thereby abolishing the critical binding site for tPA-plasminogen decreasing plasmin formation. Thus the evidence is supportive of dysregulated coagulation, and impaired fibrinolysis with a predisposition to atherothrombosis, in conditions such as the metabolic syndrome, in which there are increased concentrations of VLDL and remnant lipoproteins. The purpose of this review is to describe the current evidence supporting a procoagulant state induced by VLDL and remnant lipoproteins. The role of these lipoprotein classes in (1) platelet activation; (2) the intrinsic coagulation cascade, and (3) clot formation and fibrinolysis is discussed.
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PMID:Effects of VLDL and remnant particles on platelets. 1687 77

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.
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PMID:Global assessment of the coagulation status in type 2 diabetes mellitus using rotation thromboelastography. 1698 49

Diabetic nephropathy, a major complication of diabetes mellitus that leads to mortality, has been shown to involve a dysregulation of the coagulation system. Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on endothelial cells, is one of the molecules required to maintain the antithrombogenic properties of endothelial cells. Previously, we showed that recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity in the carotid arteries of rats. In the present study, to investigate its protective effects against diabetic nephropathy, rAN II was administered to KK-Ay mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney size, and histological glomerular lesions were investigated. The mean weight of kidneys from KK-Ay mice treated with rAN II was significantly less than that of those treated with PBS (control) (p < 0.02). Furthermore, the level of albuminuria observed in rAN II-treated KK-Ay mice was significantly less than that of the control group (rAN II, 0.90+/-0.12 microg/day; PBS, 1.55+/-0.31 microg/day; p < 0.01); also, the area of diffuse glomerular lesions was significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p < 0.01). Bleeding time, prothrombin time (PT), and active partial thromboplastin time (APTT) did not significantly differ between the two groups. Our results suggest that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice without influencing the coagulation system, indicating that annexin-2 may be considered as a possible new therapeutic tool for patients with diabetic nephropathy.
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PMID:Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability. 1720 Jul 79

Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor that is proteolytically activated by certain endogenous proteases, such as trypsin, tryptase, and factor Xa. PAR2 can also be activated by synthetic peptides if their sequence mimics the tethered ligand exposed after receptor cleavage. Although it is known that PAR2 modulates vascular reactivity, it is unclear whether at the chronic stage of type 2 diabetes there are alterations in PAR2-mediated vascular responses. We investigated this issue by exposing mesenteric artery rings to PAR2-activating peptide (PAR2-AP; SLIGRL-NH(2)), the arteries used being obtained from later-stage (32-40-week-old) type 2 diabetic Goto-Kakizaki (GK) rats. The PAR2-AP-induced relaxation was enhanced in GK rats (vs. age-matched Wistar rats), whereas the ACh-induced relaxation was weaker in GK than in Wistar rats. In both groups, the PAR2-AP-induced relaxation was largely blocked by endothelial denudation or by N(G)-nitro-L-arginine [nitric oxide (NO) synthase inhibitor] treatment, but it was unaffected by indomethacin (cyclooxygenase inhibitor) treatment. Both the NO production induced by PAR2-AP and the PAR2 protein expression were significantly increased in mesenteric arteries from GK rats (vs. Wistar rats). These data are the first to indicate that the PAR2-AP-induced endothelium-dependent relaxation is enhanced in mesenteric arteries isolated from type 2 diabetic GK rats at the chronic stage, and they further suggest that the enhancement may be due to an increased expression of PAR2 receptors in this artery.
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PMID:Mechanisms underlying enhanced vasorelaxant response to protease-activated receptor 2-activating peptide in type 2 diabetic Goto-Kakizaki rat mesenteric artery. 1954 Aug 92

The authors carried out a comparative analysis of the level of homocysteine and the state of haemostasis in patients with and without type 2 diabetes mellitus in the remote terms after endured reconstructive operations on the aorto-iliac segment. They examined a total of eighty-eight patients who had endured reconstructive operations on the aorto-iliac segment at various terms. Of these, forty-two patients were found to have a severe course of type 2 diabetes mellitus (59.9% with decompensation) and forty-six subjects without diabetes constituted the group of comparison. The average age of the patients amounted to 61.9 +/- 1.25 years, with all being smokers. The following parameters were assessed: patency of the bypasses and major arteries of the lower limbs (LL), homocysteine (Hey), fibrinolytic activity, fibrinogen, activated partial thromboplastin time (aPTT), factor XIII, thrombin time, prothrombin index, activity of antithrombin III (AIII), platelet aggregation with ADP, and glycosylated haemoglobin (Hb Aic).
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PMID:[Assessment of the level of homocysteine and the state of haemostasis in patients with and without type 2 diabetes mellitus in remote terms after reconstructive operations on the aorto-iliac segment]. 1980 38

Vascular complications are a common factor determining morbidity and mortality of diabetic patients. In vitro studies have revealed that gliclazide has antiplatelet activities. To clinically assess this action, we measured the effects of gliclazide on platelet activities and abnormal fibrinolysis in patients with type 2 diabetes mellitus. We studied 14 patients aged 38 to 72 years (9 men and 5 women) with type 2 diabetes mellitus who have been treated with glibenclamide in our hospital for more than 6 months. We switched from glibenclamide to gliclazide using the average ratio of the respective doses, 2.5 vs 40 mg. We titrated the dose of gliclazide to keep the glycemic control at the same level as the previous (glibenclamide) treatment. We measured 10 micromol/L serotonin-induced or 0.5 micromol/L adenosine diphosphate (ADP)-induced platelet aggregate formation by particle counting using light scattering at baseline and up to 6 months after the switch. After switching to gliclazide, platelet aggregate formation induced by serotonin was significantly reduced (P < .05, compared with the levels observed after glibenclamide treatment). The body mass index, fasting plasma glucose, immunoreactive insulin, homeostasis model assessment of insulin resistance, hemoglobin A(1c) (HbA(1c)), total cholesterol, triglycerides, high-density lipoprotein cholesterol, prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin-antithrombin III complex, plasmin-alpha2-plasmin inhibitor complex, and plasma plasminogen activator inhibitor type 1 (PAI-1) were not changed. In the group with improved HbA(1c) (n = 5), ADP-induced platelet aggregate formation and plasma PAI-1 level were significantly reduced (P < .05, compared with the group with aggravated HbA(1c), n = 9). Multiple regression analysis showed that percentage change of ADP-induced platelet aggregate formation (standardized beta = 0.540, P < .05) was independently associated with percentage change of plasma PAI-1 level in addition to percentage change of HbA(1c) (standardized beta = 0.657, P < .05) (R = 0.939, P < .05) after switching to gliclazide. The other independent variants, like the final dose of gliclazide, homeostasis model assessment of insulin resistance, percentage change of prothrombin time, activated partial thromboplastin time, and total cholesterol, were not significantly associated with the percentage change of plasma PAI-1 level. These results indicate that gliclazide inhibits platelet aggregation via the serotonin pathway, independently of the metabolic control per se. Furthermore, in the patients with improved glycemic control, gliclazide could inhibit ADP-induced platelet aggregation and reduce PAI-I level. Taken together, the results show that gliclazide may be more useful for the prevention of diabetic vascular complications than glibenclamide.
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PMID:Effects of gliclazide on platelet aggregation and the plasminogen activator inhibitor type 1 level in patients with type 2 diabetes mellitus. 2007 Sep 90

Antiphospholipid antibodies (aPL) are considered to be contributory factors in the development of thrombotic events. The objective of the study was to determine if aPL are involved in the pathogenesis of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. IgG anticardiolipin antibodies (IgG aCL), lupus anticoagulant (LA), and anti-IgG beta2-glycoprotein I antibodies (anti-beta2-GPI) were prospectively tested in 34 patients with DR (group 1), 20 males and 14 females, range of age 52-79 years, mean age 57 +/- 4.6 years, duration of diabetes 8-15 years, as compared to 29 type 2 diabetic patients without DR (group 2), 19 males and 10 females, range of age 54-77 years, mean age 58 +/- 4.8 years, duration of diabetes 10-13 years, and to 31 controls matched for age and sex (group 3). IgG aCL and anti-beta2-GPI were detected by enzyme-linked immunosorbent assay (ELISA) and LA was detected by activated partial thromboplastin time, kaolin clotting time, dilute Russell's viper venom time, dilute prothrombin time. Comparison between patients and controls and patients group were expressed as relative risk with its 95% confidence interval (RR [95%/CI], where a lower limit > 1.0 was considered significant. All values were determined by Fischer's exact test. A value of p < 0.05 was considered statistically significant. The incidence of IgG aCL positive (low 4-15 GPL U IgG aCL titers) in group 1 was 21/34 (62%) vs. 12/29 (41%) in group 2 (RR 1.460 95% CI [0.9052 to 2.382]), p = 0.1330. The incidence of LA positive in group 1 was 27/34 (79%) vs. 8/29 (28%) in group 2 (RR 3.086 95% CI [1.584 to 6.010]), p < 0.0001. The incidence of anti-IgG beta2-GPI positive in group 1 was 29/34 (85%) vs. 6/29 (21%) in group 2 (RR 4.640 95% CI [2.067-10.418]), p < 0.0001. The results suggest the possible participation of anti-beta2-GPI and LA in the pathogenesis of DR, shifting the hemostatic balance toward a pro-thrombotic state increasing the risk of developing thrombosis.
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PMID:Study of antiphospholipid antibodies in type 2 diabetes mellitus with and without diabetic retinopathy. 2044 42


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