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

To determine the relationship between thrombin generation and platelet secretion in vivo in diabetes mellitus, we measured simultaneous plasma beta-thromboglobulin (BTG) and fibrinopeptide A (FPA) in 40 insulin-dependent patients without renal disease, and 20 control subjects of similar age. Log mean plasma BTG and FPA were higher in diabetic patients (32.1 vs 23.7 ng/ml, and 2.83 vs 1.49 ng/ml, p less than 0.001 and less than 0.005, respectively). Neither was correlated with plasma glucose or hemoglobin AI. Plasma BTG and FPA were moderately intercorrelated in control subjects (r = +0.36, p = 0.03), but not in diabetic patients (r = +0.09, p = NS). Thus, in diabetes mellitus, thrombin generation as a contributing mechanism to platelet secretion is probably overshadowed by thrombin-independent mechanisms.
Diabetes Res 1985 Jul
PMID:Dissociation of thrombin generation and platelet secretion in diabetes mellitus. 293 51

The aim of our study was to investigate the mechanisms involved in hypoglycemia-induced platelet activation. Sixteen healthy male subjects received a 60-min intravenous infusion of human regular insulin at the rate of 64 mU . m-2 . min-1: throughout 150 min, we serially measured plasma concentrations of glucose, insulin, and counterregulatory hormones; platelet sensitivity to ADP, thrombin and platelet-activating factor; plasma concentrations of platelet markers for specific proteins of in vivo release reaction (beta-thromboglobulin and platelet factor 4). Our study showed that insulin-induced hypoglycemia causes a significant increase in platelet sensitivity to aggregating agents in vitro and a platelet release reaction in vivo. Hypoglycemia-induced platelet activation was not correlated with plasma glucose concentrations at nadir and occurred before the increase of plasma growth hormone and cortisol. To further elucidate the mechanisms of hypoglycemia-induced platelet activation, we incubated in vitro platelet-rich plasma (PRP) of seven fasting healthy subjects with the same concentrations of insulin, epinephrine, glucagon, growth hormone, and cortisol measured in vivo during insulin-induced hypoglycemia. Only epinephrine was able to increase platelet sensitivity to aggregating agents. To investigate the role of alpha-adrenergic receptors in this phenomenon, we also studied four healthy subjects on another occasion, repeating the above-described insulin infusion together with intravenous infusion of phentolamine (-15 to +150 min), 5 mg over 2 min followed by 500 micrograms/min. alpha-Blockade was able to suppress hypoglycemia-induced increase of platelet sensitivity to aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jul
PMID:Studies on mechanisms involved in hypoglycemia-induced platelet activation. 294 27

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.
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PMID:Platelet and clotting activities after cold stress in diabetic patients. 297 Jun 90

Abnormalities of haemostasis are common in diabetes mellitus. As indicators of fibrinolysis and coagulation, plasmin and thrombin activity were assessed by assay of the fibrinogen peptide derivatives B beta 15-42 and fibrinopeptide A respectively in 60 diabetic patients and 50 control subjects in a cross-sectional study. Glycosylated haemoglobin (HbA1) correlated with B beta 15-42 (r = -0.26, p less than 0.05) and fibrinopeptide A (r = 0.30, p less than 0.05) in the diabetic patients suggesting that poor glycaemic control (i.e. high HbA1 levels) was associated with depressed plasmin and enhanced thrombin activity. Compared to controls, fibrinopeptide A levels were increased in diabetics (p less than 0.001) irrespective of sex or type of diabetes. B beta 15-42 levels were normal in diabetic females but increased in diabetic men (p less than 0.001) possibly secondary to the activation of coagulation. These results suggest that in diabetes mellitus activation of coagulation is the dominant haemostatic abnormality and that better glycaemic control could influence in-vivo plasmin and thrombin activity favourably.
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PMID:Thrombin and plasmin activity in diabetes mellitus and their association with glycaemic control. 297 Dec 34

An attempt was undertaken to assess the relationship between the imbalance of lipid peroxides, thromboxane A2/prostacyclin and increased platelet aggregability during early (2 months) and late (6 months) stage of streptozotocin diabetes in rat. Thromboxane A2 and prostacyclin (PGI2) were estimated by their stable metabolic products TXB2 and 6-keto-PGF1 alpha respectively. The results showed: 1. There is a significant imbalance in TXA2 (a potent promoter of platelet aggregation) and PGI2 (a potent vasodilator and inhibitor of platelet aggregation). The ratio TXA2/PGI2 was increased by 38% in the early and by 69% in the late stage of diabetes. 2. Serum lipid peroxides increased significantly during early (four times) and late (five times) stage of diabetes. 3. There is a very good correlation between increased lipid peroxides and increased TXA2/PGI2 ratio (r = 0.71) in diabetic rats. 4. A pronounced increase in thrombin-induced platelet aggregation is consistent with the increased levels of lipid peroxides (r = 0.65) and TXA2/PGI2 ratio (r = 0.60). 5. All described changes correlate with the duration of the disease.
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PMID:Pathogenesis of cardiovascular disorders in streptozotocin-induced diabetes in rat. II. Correlation between lipid peroxides, thromboxane A2/prostacyclin, and platelet aggregation in different stages of diabetes. 306 12

Several pathways are activated when platelets aggregate and undergo the release reaction. We have examined the relative importance of these pathways in the responses to adenosine diphosphate (ADP), thrombin, or collagen of washed platelets from rats with diabetes induced by streptozocin. ADP-induced aggregation was enhanced without the release reaction with platelets from diabetic rats. Collagen-induced aggregation and release, and the adherence of platelets to collagen-coated glass were similar with platelets from diabetic and control rats. Thrombin (1 U/ml) induced more extensive loss of tritium from 3H-arachidonic acid-labeled platelets from diabetic rats than from control rats. Platelet aggregation and the release of 14C-serotonin from prelabeled platelets was greater in response to low concentrations of thrombin (0.04 U/ml). Creatine phosphate-creatine phosphokinase (CP/CPK) and aspirin completely blocked aggregation and partially blocked the release of granule contents from platelets from control and diabetic rats exposed to this low concentration of thrombin. Thus, the enhanced platelet aggregation in response to low concentrations of thrombin was likely mediated in part by released ADP and products formed from arachidonate. In contrast, with a higher concentration of thrombin (0.0625 U/ml), CP/CPK and aspirin did not inhibit the increased sensitivity of diabetic platelets to thrombin-induced aggregation and release; the concentrations of CP/CPK completely blocked aggregation induced by ADP (10 mumol/L), and the aspirin inhibited thromboxane B2 production in response to thrombin (1 U/ml) by 99%. Thus, a thrombin-induced pathway(s) of aggregation and release independent of released ADP and the products of arachidonate metabolism is enhanced in platelets from diabetic rats.
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PMID:Pathways responsible for platelet hypersensitivity in rats with diabetes. I. Streptozocin-induced diabetes. 308 May 38

The discovery of a group of spontaneously diabetic rats has made it possible to examine changes in diabetic animals in the absence of possible confounding toxic effects of diabetogenic agents. The responses of washed platelets to adenosine diphosphate (ADP), thrombin, or collagen have been compared with platelets from spontaneously diabetic rats (these rats were hyperglycemic), their nondiabetic littermates (normoglycemic), and control rats from the same colony. Platelets from the diabetic rats aggregated more extensively in response to ADP than did platelets from the nondiabetic littermates or control animals. In contrast, platelet aggregation and release of granule contents in response to a low thrombin concentration (0.05 U/ml) were greater with platelets from diabetic rats and nondiabetic littermates than with platelets from control rats. A similar effect of collagen on the release of platelet serotonin was observed. Except at low concentrations of thrombin, the enhanced sensitivity to thrombin-induced aggregation and release of granule contents from platelets from diabetic rats or their nondiabetic littermates could not be inhibited by creatine phosphate-creatine phosphokinase (CP/CPK) and aspirin (CP/CPK used at concentrations that inhibited aggregation induced by ADP [10 mumol/L] and aspirin at concentrations that inhibited thromboxane B2 production induced by thrombin [1 U/ml] by 99%). Loss of radioactivity from platelets labeled with 3H-arachidonic acid and the amount of thromboxane B2 formed in response to high concentrations of thrombin (1 U/ml) was greater from platelets from the diabetic rats or their nondiabetic littermates than from control animals. Thus the effect of diabetes on this aspect of arachidonate metabolism is not primarily determined by blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathways responsible for platelet hypersensitivity in rats with diabetes. II. Spontaneous diabetes in BB Wistar rats. 308 May 39

Twenty type II (non-insulin-dependent) poorly controlled diabetics had tests of coagulation and platelet function performed while receiving high-dose sulphonylurea therapy and at 1 and 3 months following their conversion to insulin. Although no overall change in glycaemic control (assessed by glycosylated haemoglobin) was noted, a reduction in thrombin generation was observed, as judged by a significant fall in fibrinopeptide A concentrations. No changes in factor VIII coagulant activity (VIII:C), factor VIII-related antigen or antithrombin III were found. Glycosylated haemoglobin concentrations showed significant correlations with antithrombin III and factor VIII:C, suggesting that improved glycaemic control might lead to an improvement of antithrombin III function and lower factor VIII:C concentrations. No changes in platelet function were detected. The introduction of an insulin regimen that improves glycaemic control might lead to a reversal of the 'hypercoagulable state' found in type II diabetes.
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PMID:Effect of insulin therapy on coagulation and platelet function in type II (non-insulin-dependent) diabetes mellitus. 310 3

Cultured porcine aortic endothelial cells were conditioned through two passages to mimic euglycemic and hyperglycemic conditions (5.2 mM, normal glucose; 15.6 mM, elevated glucose). After incubation with 1 microM [14C]arachidonic acid for 24 h, the cells were stimulated with 1 microM A23187 for times up to 30 min. Uptake of [14C]arachidonic acid and its distribution among cell lipids were unaffected by the increased glucose concentration. The release of eicosanoids from labeled cells and unlabeled cells was measured by reverse-phase HPLC and by RIA, respectively. Compared with cells stimulated in the presence of normal glucose concentrations, cells stimulated in the presence of elevated glucose released 62.6% less free [14C]arachidonic acid, but released 129% more 14C-labeled 15-hydroxyeicosatetraenoic acid (HETE). Increased release of 15-HETE in the presence of elevated glucose in response to A23187, bradykinin, and thrombin was confirmed by RIA. A similar increase in 5-HETE release was observed by RIA after A23187 treatment. The release of both radiolabeled and unlabeled prostanoids was equal at both glucose concentrations. The data indicate that glucose may play an important role in the regulation of release and metabolism of arachidonic acid after agonist stimulation. In the presence of elevated glucose concentrations, such as those associated with diabetes mellitus, the extent and pattern of eicosanoid release from endothelial cells is markedly altered.
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PMID:Elevated glucose alters eicosanoid release from porcine aortic endothelial cells. 314 46

Low-density lipoprotein (LDL) is known to enhance platelet sensitivity to some aggregating agents. In this study, we observed that LDL isolated from patients with insulin-dependent diabetes mellitus (IDDM) enhanced thrombin-induced platelet aggregation to a greater extent than LDL isolated from matched controls (P less than .01). Thromboxane B2 production during aggregation was also significantly more enhanced by LDL isolated from IDDM than by control LDL (P less than .01). There was no difference in the lipid composition (free and esterified cholesterol, total phospholipids, and triglycerides) of LDL isolated from diabetic and control subjects. In contrast, the extent of glycosylation of LDL isolated from diabetic patients was significantly greater than that observed in LDL from normal subjects (P less than .01), and a positive correlation (r = .605, P less than .01) between the degree of LDL glycosylation and the rate of platelet aggregation was observed. LDL glycosylated in vitro enhanced thrombin-, collagen-, and adenosine 5'-diphosphate-induced platelet aggregation to a greater extent than control LDL (P less than .01). Although LDL glycosylated in vitro was taken up by platelets to a greater extent than control LDL (P less than .05), the lipid composition (free cholesterol and phospholipid) of platelets was not significantly changed. We postulate that an increased degree of glycosylation of LDL may enhance its uptake by platelets and lead to increased platelet reactivity to aggregating agents, probably by altering the structure of the platelet membrane. The enhancement of platelet aggregation by LDL may contribute to the accelerated development of atherosclerosis in diabetes mellitus.
Diabetes 1988 Dec
PMID:Enhancement of platelet aggregation by low-density lipoproteins from IDDM patients. 319 39


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