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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A possible association between plasma coagulant activity and the presence of vascular complications in patients with diabetes mellitus was studied by measuring the generation of thrombin in plasma of 20 control subjects and 50 diabetic patients classified according to the presence or absence of microvascular complications. Thrombin production was determined in defibrinated plasma using a semi-automated technique with measurement of thrombin activity using chromogenic peptide S2238. Values determined were the lag time to appearance of thrombin activity and time taken to generate 50% maximal thrombin activity. Thrombin activity was related to concentrations of coagulant factor VIII activity and fibrinopeptide A and these were correlated with HbA1C levels. The median time to generate 50% maximal thrombin activity was not significantly reduced in diabetic patients compared with control subjects (53 vs 54 s, p = 0.076) and there were no significant differences between patients with and without microvascular complications. There were no differences in median fibrinopeptide A concentrations between the diabetic and control subjects (1.5 vs 2.2 nmol/l, p = 0.169). Time to 50% maximal thrombin activity correlated inversely with factor VIII:C concentrations in diabetic patients (r = -0.344, p = 0.015, n = 50) and both this and lag time correlated with factor VIII:C in diabetic patients and control subjects combined (r = -0.395, p less than 0.01; r = -0.327, p = 0.006, n = 70). Factor VIII:C concentrations increased with age of the subject and with HbA1C concentrations. The results failed to show enhancement of coagulation in contact-activated diabetic plasma compared with control plasma and suggest that a relationship between high levels of factor VIII:C in diabetes and the development of mcirovascular complications is unlikely to be mediated through procoagulant activity in plasma.
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PMID:Generation of thrombin activity in relation to factor VIII:C concentrations and vascular complications in type 1 (insulin-dependent) diabetes mellitus. 139 82

Platelets from diabetic humans and animals have been found previously to be hypersensitive to agonists, including thrombin, in vitro but it is unclear if this hypersensitivity also occurs in vivo and leads to a greater thrombotic tendency. In the present study, the effect of diabetes was examined on thrombus formation and vessel wall responses which result from continuous intimal injury induced by indwelling aortic catheters in rabbits. Platelet and fibrin(ogen) associated with the thrombus and damaged aortae were examined. Control or alloxan-induced diabetic rabbits (9-12 months after initial treatment) were injected with 51Cr-labeled autologous platelets and 125I-labeled fibrinogen (prepared from control rabbits) before insertion of indwelling aortic catheters. The anesthetized rabbits were perfused-fixed after 20 hr or 4 days. The dry weight of thrombus that formed was determined and platelet and fibrin(ogen) accumulation in thrombi and on injured aortae were calculated from the associated 51Cr and 125I, respectively. In diabetic rabbits, more platelets accumulated in the thrombi which formed after either 20 hr or 4 days, although the weight of thrombus and net fibrin(ogen) incorporation into the thrombus were not different from corresponding control rabbits. Net platelet and fibrin(ogen) association with the injured aortae were not different between control and diabetic rabbits. It is likely that the increased platelet accumulation in arterial thrombi in diabetic rabbits which results from continuous injury to aortae is a consequence of hypersensitivity of these platelets to thrombin generated in the thrombus and at the sites of vessel injury.
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PMID:Increased platelet, but unaltered fibrinogen, accumulation in experimental thrombi in alloxan-induced diabetic rabbits. 142 57

Fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (FPB beta 15-42) and other coagulation factors (anti-thrombin III, thrombin-antithrombin complex, alpha 2-macroglobulin, plasmin inhibitor complex) were measured in the plasma of 101 patients with diabetes mellitus (DM). The levels in 80 healthy adults were also measured for comparative purposes. The mean levels of FPA, FPB beta 15-42 and the other 4 coagulation factors in the DM patients were significantly higher than in the controls (p < 0.05). The mean levels of FPA and FPB beta 15-42 in patients with diabetic retinopathy (DR) were higher than in those without DR, that is in those with proliferative diabetic retinopathy (PDR) higher than in those with simple diabetic retinopathy (SDR). In patients after panretinal photocoagulation (PRP), the mean level of FPA was higher and that of FPB beta 15-42 was lower than in patients before PRP. In the SDR group, the level of FPB beta 15-42 was significantly correlated with the progression of diabetic retinopathy. We suggest that there was a close correlation between plasma FPA and FPB beta 15-42 levels and activity or progression of disease, and that the investigation of these levels may be useful for the judging of prognosis or effect of therapies of diabetic retinopathy.
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PMID:[Plasma fibrinopeptide A, fibrinopeptide B beta 15-42 and 4 other coagulation factors levels in patients with diabetic retinopathy]. 147 75

Platelet intracellular Ca++ ([Ca++] i) was measured by flow cytometry, using a new Ca(++)-sensitive fluorescent dye, fluo 3. The acetoxymethyl derivative of fluo 3, fluo 3 AM, was incorporated into platelets most efficiently in the presence of 1.5 micrograms/ml pluronic F-127, a surfactant often used to facilitate intracellular incorporation of lipophilic agents. [Ca++] i measurement with flow cytometry proved to be more sensitive than that with ordinary fluorescence spectrophotometers, detecting cells with elevated [Ca++] i at much lower agonist concentrations. Two-dimensional analysis using forward scatter intensities and [Ca++] i more clearly defined a subset of platelets responsive to low concentrations of agonists. In normal subjects [Ca++] i hardly changed in response to low-dose thrombin (0.002 U/ml), while it invariably showed a marked increase in response to high-dose thrombin (0.02 U/ml). Thus, these dose of thrombin were used to evaluate clinically whether platelets was hyper-reactive or hypo-reactive. Of 44 patients with diabetes mellitus, 6 patients had hypo-responsive platelets, while platelets were sensitive to low concentrations of thrombin in 3 patients. Since such differences cannot be detected by conventional spectrophotometric methods, [Ca++] i measurement by flow cytometry may prove useful tool for clinical evaluation of platelet function.
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PMID:[Evaluation of platelet intracellular calcium ion concentrations with flow cytometry]. 151 79

The purpose of the study was to test whether APC: alpha 1AT complex is a useful clinical marker of the activation of coagulation. The rationale for this is that activated protein C may appear in circulation at an early stage of blood coagulation, when subcoagulant amounts of thrombin are formed. Given the relatively higher half-life of APC: alpha 1AT as compared to that of thrombin:AT-III (TAT) complexes, we hypothesized that APC:alpha 1AT could represent an amplification of the thrombin generated in the first events of coagulation. Using sandwich ELISA's we measured APC: alpha 1AT and TAT complexes as well as complexes of AT-III with its target proteases in normal subjects and in several clinical groups of patients prone to thrombotic episodes, including pregnancy, preeclampsia, hemodialysis, gynecological tumors, diabetes and oral contraceptives. APC: alpha 1AT complex was significantly increased in all clinical groups as compared to normal subjects and showed relatively higher increases than did TAT and ATM complexes in the majority of the groups studied. There was a significant and positive correlation between APC: alpha 1AT and TAT complex levels in the majority of the groups, as well as between TAT and ATM and between APC: alpha 1AT and ATM complex levels. We conclude that APC: alpha 1AT complex can be used as a sensitive marker of prethrombotic states.
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PMID:Activated protein C: alpha 1-antitrypsin (APC: alpha 1 AT) complex as a marker for in vitro diagnosis of prethrombotic states. 152 6

Several studies suggest that diabetes is associated with a hypercoagulable state. Therefore determination of thrombin-antithrombin complex (TAT) could represent a sensitive parameter for specific detection of a latent activation of the clotting system. The present study documents increased plasma TAT in a heterogeneous group of non-insulin-dependent diabetic patients. The finding of increased TAT levels both in diabetic patients with vascular complications and in vascular disease patients without diabetes suggests a relationship between existing vascular disease and the hemostatic mechanism that produces augmented thrombin activity. In acute vascular occlusions the presence of diabetes seems to increase activation of the coagulative system.
J Diabetes Complications
PMID:Thrombin-antithrombin III complexes in type II diabetes mellitus. 156 62

The influence of a disturbed hemostasis as one of the causes of retinal vein occlusions is still controversial. We investigated the functional state of the coagulation system in 16 patients, 7 with a nonischemic and 9 with an ischemic retinal vein occlusion, with an enzyme-linked immunosorbent assay for the determination of thrombin-antithrombin III complex (TAT). Patients with a history of thromboembolic disease, raised blood pressure and/or badly managed diabetes mellitus were excluded from the investigations. In healthy individuals the plasma concentration is 1.45 ng/ml +/- 0.4 (mean value +/- SD), ranging from 1.0 to 4.1 ng/ml. In our patients we measured TAT concentrations ranging from 2.0 to 48.0 ng/ml. In 2 of 7 plasma samples from patients with nonischemic retinal vein occlusion (2.1-6.3 ng/ml, mean = 3.3, SE +/- 0.6) and in 6 of 9 in ischemic retinal vein occlusion (2.0-48.0, mean = 13.2, SE +/- 5.1) TAT concentrations were found to be increased. These data indicate that disturbed hemostasis may be involved in retinal vein occlusion, especially that caused by ischemia. Furthermore, TAT may be useful in differentiating ischemic from nonischemic retinal vein occlusion.
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PMID:[Thrombin-antithrombin III complex. Cause of venous vascular occlusion of the retina]. 158 96

Plasma levels of thrombomodulin (TM), fibrinogen, antithrombin III (ATIII) and thrombin ATIII complex (TAT) were studied in healthy young subjects (group A), healthy elderly subjects (group B) and patients with level of TM in group B tended to be higher than that in group A. Levels of TM, fibrinogen and TAT in group C suggested the presence of a hypercoagulable state. When group C was further divided into those with and without diabetes mellitus (DM), the TM level in the former tended to be higher than that in the latter. Furthermore, among the patients with DM, those with diabetic retinopathy showed significantly higher levels of TM than those without retinopathy. Thus, high TM levels indicate the presence of endothelial injury. In groups B and C, TM correlated positively with fibrinogen, and negatively with ATIII, which also indicates that a high TM level is related to a hypercoagulable state. In conclusion, the TM level is considered to be a potential marker of the presence of endothelial injury.
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PMID:[Plasma thrombomodulin levels in elderly subjects]. 165 30

We have examined thrombin-induced metabolism of phosphoinositides in the platelets from fifteen NIDDM (non-insulin-dependent diabetes mellitus) patients and fifteen healthy subjects (control). The diabetic patients were divided into two groups. One group (group I) had diabetic retinopathy (microangiopathy) and the other group (group II) had atherosclerosis of great vessels (macroangiopathy). In platelets incubated with [32P] orthophosphate for 80 min, the incorporation of 32P radioactivity into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was significantly lower in the group II than in the control. The addition of thrombin induced a marked decrease in PIP2 radioactivity at 10 sec in platelets from group I compared with that from the control. These results suggest that the breakdown of polyphosphoinositides is increased in platelets from diabetic subjects with retinopathy, and also that the formation of polyphosphoinositides is decreased in the platelets from diabetic subjects with macroangiopathy.
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PMID:Thrombin-induced breakdown of phosphoinositides in platelets from patients with NIDDM. 165 98

We evaluated thrombin-induced inositol phosphate accumulation in [3H]inositol-labeled platelets prepared from patients with non-insulin-dependent diabetes mellitus. There were no significant differences in [3H]inositol incorporation into and contents of phosphoinositides between the diabetic patients and their age-matched control subjects. Thrombin induced a dose- and time-dependent accumulation of inositol phosphate. The accumulation of [3H]inositol trisphosphate and [3H]inositol bisphosphate by thrombin stimulation were significantly enhanced in platelets from the diabetic patients, although the accumulation of [3H]inositol monophosphate did not differ between the diabetic patients and the control subjects. In addition, the platelet aggregation rate induced by thrombin was also significantly enhanced in the diabetic patients in correlation with the enhanced inositol phosphate accumulation. These results suggest that increased inositol phosphate accumulation may cause accelerated platelet functions in diabetes mellitus.
Diabetes Res Clin Pract 1991 Oct
PMID:Increased inositol phosphate accumulation in platelets from patients with NIDDM. 166 Aug 5


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