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

Specific thromboxane synthetase inhibition is associated with a significant fall in abnormal albumin excretion rate in insulin-dependent diabetics (IDDs). This may be due to an effect on haemostasis or changes in renal blood flow. We have studied the effect of a specific thromboxane synthetase inhibitor, UK-38,485, on coagulation parameters in 15 IDDs, at -8, 0, 8 and 16 weeks after double blind administration of drug or placebo. Serum thromboxane B2 fell in the drug group (695 +/- 205 vs 134 +/- 180 pg/ml, n = 7, p less than 0.001), but not in the placebo group (713 +/- 409 vs 614 +/- 178 pg/ml, n = 8). The drug group showed significant reduction in adrenaline primary maximum (24 +/- 7 vs 37 +/- 7%, p less than 0.05) and ADP maximum (71 +/- 14 vs 81 +/- 7%, p less than 0.05) aggregation not seen in the placebo group. Dilute whole blood clot lysis time was, however, increased in the drug group (7.1 +/- 1.6 vs 6.25 +/- 2.4 hr, p less than 0.05) and no effect was observed in either group on in vivo parameters of platelet aggregation (beta-thromboglobulin, platelet factor 4 and platelet micro-aggregates). We conclude that specific thromboxane synthetase inhibition is probably not associated with an overall improvement in haemostasis and the clinical effects observed cannot be explained on this basis.
Diabetes Res 1986 Sep
PMID:Specific thromboxane synthetase inhibition and haemostasis in insulin-dependent diabetics. 294 9

Thrombotic events may occur in patients who present with severe uncontrolled diabetes or with diabetic coma. As a possible explanation for this, platelet function was investigated at presentation with diabetic ketoacidosis and during treatment in 10 patients. Concentrations of the platelet-specific proteins, platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) were elevated and fell towards normal with treatment. Despite evidence of increased aggregation in vivo, platelets from subjects with ketoacidosis were insensitive to adenosine 5'-diphosphate (ADP), sensitivity increasing with correction of ketoacidosis. Platelets from ketoacidotic diabetics were initially insensitive to the anti-aggregatory action of prostacyclin (PGI2) and became normal with treatment. Initial blood glucose concentrations correlated with log10 ADP concentrations (r = 0.72, p less than 0.01) and with log10 PGI2 ID50 (the PGI2 concentration required to half-inhibit ADP-induced aggregation) (r = 0.66, p less than 0.025). Glucose concentrations throughout the 2-week study period correlated with all log10 ADP concentrations (r = 0.32, p less than 0.005) and all log10 PGI2 ID50 concentrations (r = 0.51, p less than 0.001). The decrease in ADP sensitivity in ketoacidosis, paradoxical in view of the evidence of increased in vivo platelet aggregation, may result from an acquired platelet storage pool deficiency.
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PMID:Paradoxical platelet behaviour in diabetic ketoacidosis. 295 Nov 59

Serum levels of apolipoprotein B were measured, and investigations of the platelet function were carried out in 32 patients with insulin-dependent diabetes and in 34 healthy controls similar in age. Mean serum levels of apolipoprotein B were 1.51 g/l in the diabetic patients and 1.18 g/l in the control group, and this difference was significant. In the diabetic patients a secondary wave of aggregation was more easily induced by low concentrations of adenosine diphosphate or adrenaline. It was also possible to induce 50% of maximal aggregation by lower concentrations of adenosine diphosphate or arachidonic acid in these patients, and their number of circulating platelet aggregates increased. Plasma levels of beta-thromboglobulin and platelet factor 4 were raised and, in the presence of N-ethyl maleimide, platelets from diabetic patients produced significantly more malondialdehyde than those from normal controls. The relationship between increased serum levels of apolipoprotein B and platelet hyperreactivity may be more than accidental and should be studied further to elucidate its possible implication with platelet function and atherogenesis.
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PMID:Apolipoprotein B and platelet function in diabetes mellitus. 295 58

Human plasma contains a factor capable of stimulating vascular prostacyclin generation even in atherosclerotic vessels with minimal in-vitro capacity for PGI2-synthesis. The activity of this prostacyclin stimulating plasma factor (PSPF) has been reported to be elevated in renal failure and hepatic coma. We are not aware of any data as to whether this PSPF plays a role in maintaining hemostatic balance in patients with peripheral vascular lesions. Therefore, we examined 62 patients with peripheral vascular disease (PVD). This study group was subdivided into normo- and hyperlipemic subjects, patients with and without maturity onset diabetes, and plasma beta-thromboglobulin levels higher and lower than 50 ng/ml. 10 healthy sex and age matched persons served as controls. Vascular prostacyclin formation was studied in vitro after incubation of the patients' plasma and a buffer control with various tissue samples (human femoral artery, rat abdominal and thoracic aorta of healthy and of streptozotocin induced diabetic animals, swine endothelial layer and remaining tissue (media and adventitia) and cultured endothelial (EC) and smooth muscle cells (SMC) of minipig arota. In addition, 6-oxo-PFG1 alpha formation by cultured EC and SMC (minipig aorta source) after incubation with tris HCl-buffer or plasma were estimated by means of specific radioimmunoassays. In general, tissue samples and cells incubated in plasma exhibit a marked increase of in-vitro PGI2-formation as compared to buffer. No difference could be found between PSPF of CHD-patients and healthy controls. Similar findings were obtained using incubated vascular tissue and cultured cells by means of the bioassay and specific RIA, respectively. These findings indicate that the PSPF does not seem to be of any clinical relevance in hemostatic regulation in patients with advanced atherosclerosis.
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PMID:Prostacyclin synthesis stimulating plasma factor in patients with peripheral vascular disease. 295 84

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

There are conflicting reports of platelet function abnormalities in diabetic patients without vascular complications. We have studied in vitro platelet aggregation, using platelet rich plasma and whole blood techniques, in 18 patients with uncomplicated insulin-dependent diabetes and a matched group of 24 non-diabetic subjects. In addition we measured plasma beta-thromboglobulin levels in these groups, as an index of in vivo platelet activation, and compared the indices of in vitro and in vivo platelet function before and after maximal bicycle exercise. Before exercise plasma beta-thromboglobulin levels and platelet sensitivities to ADP, collagen or adrenaline, as assessed by both methods of platelet aggregation, were the same in diabetic and control subjects. Both groups showed similar increases in beta-thromboglobulin levels and in platelet sensitivity to all agonists in whole blood following exercise. Using platelet rich plasma there were no changes in platelet sensitivity in either group after exercise. In non-diabetic subjects, increases in noradrenaline levels after exercise correlated with increases in platelet sensitivity to adrenaline in whole blood. This was not observed in the diabetic group. Abnormalities of platelet function, using the techniques described here, are not present in diabetic patients who do not have clinical evidence of vascular disease.
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PMID:Platelet function in uncomplicated insulin-dependent diabetic patients at rest and following exercise. 297 Sep 23

The effect of 24 hours and 7 days treatment with nisoldipine (10 mg, twice daily) on platelet function was studied in 12 normotensive volunteers of whom six were insulin-dependent diabetics without clinical evidence of vascular complications. Platelet aggregation was assessed by platelet rich plasma (PRP) and whole blood (WB) techniques. In addition, the effect of nisoldipine on platelet hyperaggregability following exercise was assessed. After taking nisoldipine for 24 hours, in vitro platelet hypersensitivity to adenosine diphosphate was observed in PRP (p less than 0.01) and WB (p less than 0.01), to adrenaline in WB (p less than 0.03), and to collagen in PRP (p less than 0.02). After seven days treatment, platelet sensitivities to all agonists at rest in both PRP and WB showed no differences from pre-treatment values. Exercise-induced platelet hypersensitivity in WB to all three agonists was unchanged after nisoldipine treatment. Plasma noradrenaline and adrenaline concentrations increased after 24 hours treatment, although changes in agonist EC50s at 24 hours were not related to changes in plasma catecholamine levels. No effects of nisoldipine were observed on platelet thromboxane B2 release in PRP, or on plasma beta-thromboglobulin levels. No differences in the effects of nisoldipine were observed between diabetic and non-diabetic subjects. Nisoldipine treatment for seven days is not associated with altered platelet function, but platelet hypersensitivity is observed after treatment for 24 hours in both insulin-dependent diabetics and controls.
Diabetes Res 1988 Jul
PMID:Ex vivo platelet studies following oral nisoldipine in normotensive insulin-dependent diabetics and non-diabetic controls. 297 36

A study was conducted to determine the effects of glibenclamide on serum lipoproteins, apolipoproteins, thromboxane (TXA2), prostacyclin (PGI2), and beta-thromboglobulin (B-TGL) in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). In 20 NIDDM patients, aged 34 to 67 (mean, 53.6) years, without clinical signs of atherosclerotic disease and whose blood sugar level was over 140 mg/dl after four weeks of dietary treatment, fasting blood samples were taken before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glibenclamide treatment. Pretrial levels of total serum cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the diabetic patients did not differ from those in nondiabetic controls, whereas high-density lipoprotein cholesterol (HDL-C) levels and the percentage of TC bound to HDL (HDL-C%) were significantly lower in the patients than in controls. After combined dietary and glibenclamide treatment and the normalization of blood sugar, both HDL-C (mg/dl) levels and HDL-C% levels increased significantly. TC, TG, and LDL-C levels decreased. Levels of apolipoproteins A1 and A2 rose and apolipoprotein B fell, but differences were not significant. TXB2 and 6-keto-PGF1-alpha (the inert metabolites of TXA2 and PGI2) and B-TGL were determined by radioimmunoassay. TXB2 and B-TGL levels decreased significantly after glibenclamide administration, indicating attenuation of platelet aggregation. No changes in PGI2 were observed. The results demonstrate the favorable effect of glibenclamide on lipoproteins and apolipoproteins in NIDDM patients, especially in increasing HDL-C levels and HDL-C%, and in attenuating platelet aggregation as indicated by reduction of TXB2 and B-TGL.
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PMID:Effects of glibenclamide on serum lipids, lipoproteins, thromboxane, beta-thromboglobulin, and prostacyclin in non-insulin-dependent diabetes mellitus. 297 74

The effects of alpha 2-adrenergic-receptor blocker mianserin on the responses of blood glucose, plasma beta-thromboglobulin (beta-TG), and various counterregulatory hormones to insulin-induced hypoglycemia were studied in nine healthy male subjects. The alpha 2-adrenoceptor-blocking action of mianserin was confirmed by its inhibitory effect on platelet activation in vitro. Mianserin was given orally 90 min before insulin injection; the same study without mianserin was performed on another day as the control study. The time courses of blood glucose and serum C-peptide (0, 20, 45, and 180 min after the insulin injection) were identical in both studies, indicating that mianserin has no effect on these parameters. However, a significant increase of beta-TG at 45 min after insulin injection was completely suppressed by the administration of mianserin (mean +/- SE, 68.5 +/- 6.0 vs. 28.8 +/- 7.6 ng/ml, n = 6, P less than .05). No significant differences were obtained between the two studies in the responses of plasma or serum catecholamines, cortisol, glucagon, growth hormone, thromboxane B2, and 6-ketoprostaglandin F1 alpha. These results suggest that epinephrine is responsible for some, if not all, of the beta-TG release from the platelets during insulin-induced hypoglycemia.
Diabetes 1987 Apr
PMID:Role of alpha 2-adrenergic receptor in platelet activation during insulin-induced hypoglycemia in normal subjects. 302 89

The role of epinephrine in platelet activation and the effect of an alpha 2-adrenoceptor antagonist, midaglizole, during insulin-induced hypoglycaemia in Type 2 (non-insulin-dependent) diabetes mellitus were examined. The action of midaglizole as a platelet alpha 2-antagonist was confirmed by in vitro studies using platelet-rich plasma and washed platelet suspension. Hypoglycaemia was induced by a bolus injection of short-acting insulin in 24 diabetic patients. They were divided into two groups, a control group (n = 12) and an alpha 2-group (n = 12), and midaglizole was administered orally 60 min before insulin injection in the latter. Blood glucose and plasma C-peptide levels were significantly decreased (p less than 0.005) by insulin injection in both groups. Counter-regulatory hormones, including epinephrine, and arginine vasopressin were similarly increased at the hypoglycaemic nadir compared with the levels at 0 min in both groups. Plasma beta-thromboglobulin was increased at the hypoglycaemic nadir (165.5 +/- 12.6 ng/ml) compared with the level at 0 min (121.0 +/- 11.5, p less than 0.005) in the control group, whereas no significant increase was demonstrated in the alpha 2-group. These results suggest that plasma epinephrine plays an important role in platelet activation during hypoglycaemia in Type 2 diabetes mellitus, and that the platelet activation is prevented by alpha 2-adrenoceptor antagonist.
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PMID:Effect of alpha 2-adrenoceptor antagonist on platelet activation during insulin-induced hypoglycaemia in type 2 (non-insulin-dependent) diabetes mellitus. 306 33


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