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

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

Vitamin E deficiency is associated with increased platelet aggregation, which can be normalized through vitamin E supplementation. In diabetes, increased platelet thromboxane A2 (TXA2) production is correlated with decreased platelet vitamin E content. We therefore investigated the effect of 400 mg DL-alpha-tocopherol acetate daily for 4 wk on ADP- and collagen-induced platelet aggregation and platelet TXA2 production in 22 type I (insulin-dependent) diabetic patients without macroangiopathy and with no or only minimal microangiopathy by a double-blind placebo-controlled crossover study. Platelet aggregation was induced in platelet-rich plasma by two or three different concentrations of ADP and collagen. TXA2 was measured by the stable spontaneous breakdown product thromboxane B2 by a specific radioimmunoassay. Whereas metabolic control remained unchanged during the study period, platelet TXA2 production was significantly (P less than .05 and P less than .01) reduced at each ADP concentration and at two of three collagen concentrations. Because increased TXA2 production of diabetic platelets is thought to play an important pathogenetic role in diabetic angiopathy, we conclude that vitamin E treatment could be beneficial with respect to platelet-vessel-wall interaction and thus might be promising for the prevention of diabetic angiopathy.
Diabetes 1988 Sep
PMID:Effect of vitamin E supplementation on platelet thromboxane A2 production in type I diabetic patients. Double-blind crossover trial. 304 91

Previous studies have suggested that the sulphonylurea hypoglycaemic agent gliclazide has specific effects in inhibiting platelet aggregation, and other haemorrheological effects that could be beneficial in preventing diabetic microangiopathy. A double-blind trial of the effect of gliclazide on platelet aggregatory responses was performed in 51 diabetic patients. Insulin- and non-insulin-treated diabetics were assessed during an initial 12-month placebo period, and in a subsequent 24-month active period after randomisation into placebo and gliclazide groups in insulin-treated patients or to glibenclamide and gliclazide groups in non-insulin-treated patients. Platelet-rich plasma was obtained from patients at intervals of at least 6 months during the trial. Circulating platelet aggregates were estimated, platelet aggregation was studied in response to three concentrations of adrenaline, ADP and collagen and thromboxane B2 produced by platelets exposed to collagen was measured. No significant effect of gliclazide was demonstrated on any parameter of platelet function evaluated.
Diabetes Res Clin Pract 1988 Jan 07
PMID:Lack of effect of gliclazide on platelet aggregation in insulin-treated and non-insulin-treated diabetes: a two-year controlled study. 312 29

The Ivanovas-Sieve (IVA-SIV) rat represents the only available animal model of endogenous hypertriglyceridemia, in the absence of obesity and/or overt diabetes. Since plasma lipids/lipoproteins can modulate platelet reactivity and eicosanoid metabolism, these were examined in two groups of Charles River (CR) and IVA-SIV rats of identical age. The IVA-SIV rats had 2-fold higher plasma triglycerides and a 55% higher number of circulating platelets; the number of platelets was significantly correlated with triglyceridemia. Platelet reactivity to ADP and to collagen was significantly reduced in these animals, whereas the formation of thromboxane B2 did not differ from that of the CR. After perfusion of platelet-rich plasma (PRP) through the aortas of animals of the two strains, platelet aggregability, already lower in the IVA-SIV, was reduced to a higher extent compared to the CR. Increased levels of the prostacyclin metabolite 6-keto-PGF1 alpha were identified in the perfusate from the aortas of IVA-SIV rats. Platelets from these animals also showed an increased sensitivity to Iloprost, a stable prostacyclin analogue, with an IC50 1.7-fold lower compared to CR rats. Spontaneous hypertriglyceridemia in the IVA-SIV model is not associated with platelet hyperresponsiveness, but rather with a reduced sensitivity to major aggregants.
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PMID:Reduced platelet aggregability and increased vascular prostacyclin formation in a variant rat strain (IVA-SIV) with endogenous hypertriglyceridemia. 321 76

It has been proposed that the development of diabetic complications may involve a depletion of cellular myo-inositol due to an increase in polyol (sorbitol) formation. We therefore initially examined the effect of diabetes on levels of these metabolites in isolated cerebral microvessels. Compared with microvessels from control rats, microvessels from diabetic animals showed no detectable alteration in myo-inositol levels and a small increase in sorbitol content. To assess whether myo-inositol depletion might occur in only certain microvascular cells, cultured bovine cerebral microvascular pericytes and endothelium were grown for 3 or 18-20 days at 1.1, 5.5, or 22.2 mmol/l glucose. Increased medium glucose concentration resulted in increased sorbitol content in both cell types after both periods of incubation (p less than 0.05). In contrast, a significant decrease in myo-inositol content (22%, p less than 0.01) was observed only in pericytes grown for 18-20 days in the high glucose medium. Neither the adenosine 5'-triphosphate content nor the adenosine 5'-triphosphate/adenosine 5'-diphosphate (ATP/ADP) ratio of the pericytes was affected by the medium glucose concentration, indicating that the decrease in myo-inositol was not caused by a deficiency in the cellular energy state affecting the active transport of myo-inositol. These data suggest that myo-inositol depletion occurs selectively in the pericyte, a cell type known to be the site of early morphological changes in diabetes. Furthermore, the depletion apparently requires prolonged exposure to high glucose and is not due to a change in energy state.
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PMID:Chronic exposure to high glucose decreases myo-inositol in cultured cerebral microvascular pericytes but not in endothelium. 324 Aug 40

We investigated triglycerides, total cholesterol, HDL cholesterol, the fatty acid patterns of serum triglycerides, cholesterol esters and phospholipids in relation to the ADP induced platelet aggregation in 34 long-term insulin-dependent diabetic patients with an extremely long diabetes duration of about 40 years. The concentrations of triglycerides, total cholesterol and HDL cholesterol of the patients did not differ from those of an age-matched non-diabetic control group. In the insulin-dependent diabetics the percentages of arachidonic and eicosapentaenoic acid in both serum cholesterol esters and phospholipids were decreased in comparison with control subjects. No difference was observed with respect to the ADP induced platelet aggregation between long-term diabetics and controls. The findings demonstrate that type I diabetic patients with an extremely long duration of diabetes are not characterized by increased serum lipids or platelet aggregation, both being well known risk factors for macroangiopathy. However the decreased portions in eicosanoid synthesis precursors may indicate a disturbed fatty acid metabolism.
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PMID:Relationship between fatty acid pattern and platelet aggregation in long-term insulin-dependent type I diabetics. 324 13

The results are presented of a controlled study in male Wistar rats into the effects of 24R,25-dihydroxyvitamin D3 on blood glucose levels, bone calcium content and ADP-induced platelet aggregation in streptozocin-induced diabetes mellitus. Blood glucose levels were shown to be decreased by 10 micrograms/kg 24R,25-dihydroxyvitamin D3. The reduced bone calcium content associated with diabetes mellitus was returned to normal levels with both 1 and 10 micrograms/kg 24R,25-dihydroxyvitamin D3. It was also shown to exhibit dose-dependent anti-platelet activity. The data suggest that 24R,25-dihydroxyvitamin D3 might have potential as a mild therapeutic agent in the treatment of osteoporosis and platelet hyperactivity associated with diabetes mellitus.
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PMID:Effect of 24R,25-dihydroxyvitamin D3 in experimental diabetic rats. 326 45

It has been speculated that platelet activation may contribute to the evolution of vascular complications in patients with Type I diabetes mellitus. To address this hypothesis, we measured the plasma and urinary metabolites of thromboxane, presumably of platelet origin, and of prostacyclin, derived from endothelial cells, in addition to more conventional indexes of platelet function. Urinary excretion of the metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha did not differ between diabetics with or without retinopathy and nondiabetic controls. Furthermore, measurement of platelet granule constituents, the aggregation responses to ADP or arachidonic acid, and levels of serum thromboxane B2 failed to discriminate between the groups. The institution of tight diabetic control with multiple daily injections of insulin failed to alter either urinary metabolite excretion or plasma levels of 11-dehydro-thromboxane B2. Conversely, insulin-induced hypoglycemia failed to alter the concentrations of plasma or urinary thromboxane metabolites in nondiabetic volunteers, despite a mean 60-fold increase in plasma epinephrine. These studies suggest that platelet activation does not precede the development of microvascular complications in patients with Type I diabetes who lack clinical evidence of macrovascular disease and have normal renal function. Furthermore, it is unlikely that platelet activation due to intermittent hypoglycemia contributes to the reportedly accelerated development of retinopathy in such patients, when they are subject to tight diabetic control.
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PMID:Thromboxane biosynthesis and platelet function in type I diabetes mellitus. 329 13

The development of insulin-dependent diabetes mellitus is thought to be dependent on either the autoimmunity or the interaction of environmental agents with the pancreatic beta cells, or both in a genetically susceptible host. As environmental factors affecting the induction of type I diabetes, diabetogenic chemicals and viruses are likely candidates as primary injurious agents for pancreatic beta cells in man and animal. A number of structurally diverse chemicals including alloxan, streptozotocin, chlorozotocin, vacor, and cyproheptadine are diabetogenic mainly in rodents and sometimes in man. The possible mechanisms for the beta cell destruction by these chemicals include (a) generation of oxygen free radicals and alteration of endogenous scavengers of these reactive species; (b) breakage of DNA and consequent increase in the activity of poly ADP ribose synthetase, and enzyme depleting NAD in beta cells; and (c) inhibition of active calcium transport and calmodulin-activated protein kinase activity. Regarding viruses, a number of different viruses including encephalomyocarditis virus, Mengovirus, Coxsackie B viruses, and Reoviruses can infect and destroy pancreatic beta cells mainly in rodents and sometimes in humans. In the murine model, the development of encephalomyocarditis and Coxsackie B virus-induced diabetes is dependent on the genetic background of the host and the genetic makeup of the virus. Mengo-2T virus has caused diabetes in strains of mice resistant to encephalomyocarditis virus-induced diabetes. In contrast to encephalomyocarditis virus, Coxsackie B viruses, and Mengovirus, reovirus type 1 seems to be somewhat associated with an autoimmune response in the induction of diabetes. In addition to the murine model, cotton rats become diabetic when inoculated with Mengovirus 2T. Furthermore, cumulative environmental insults with Coxsackie B viruses and chemicals result in diabetes in non-human primates. In man, there may be 2 possible roles for viruses in the pathogenesis of insulin-dependent diabetes mellitus. The one is acute cytolytic infection of beta cells (e.g., Coxsackie B viruses), which may sometimes induce diabetes in genetically predisposed individuals, and the other one is slow and persistent infection (e.g., congenital cytomegalovirus and Rubella), which may induce autoimmunity, leading to type I diabetes.
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PMID:Effects of environmental factors on the development of insulin-dependent diabetes mellitus. 331 67

ATP, ADP, phosphocreatine (PCr), creatine (Cr), glucose, malate, sorbitol, and myo-inositol (MI) were measured by quantitative histochemical techniques in pure neuroectodermal tissue of rat embryos of gestation days 11 and 12 that were dissected from normal and streptozocin-induced diabetic mothers. Neither gestational age nor maternal diabetes affected the tissue's energy potential (ATP-to-ADP and PCr-to-Cr ratios). Diabetes resulted in a fourfold rise in the embryonic glucose and a 25% increase in neuroectodermal malate content. Maternal hyperglycemia caused a rise in fetal sorbitol at days 11 and 12 of gestation. The MI content of the neuroectoderm was not affected by the maternal diabetic state in perfusion embryos (day 11); however, the near doubling of MI that occurs from day 11 to day 12 during normal development was prevented. Thus, embryos isolated from diabetic mothers on gestation day 12 had 30% less MI than embryos isolated from normal mothers. From these data we conclude that a rise in tissue sorbitol is not always accompanied by a fall in tissue MI. These results and recent information in the literature implicate involvement of decreased MI concentrations in the process leading to malformation of the nervous system in diabetic embryopathy.
Diabetes 1988 Jul
PMID:Diabetes affects sorbitol and myo-inositol levels of neuroectodermal tissue during embryogenesis in rat. 338 92


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