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

To investigate the possible relevance of free radicals and prostanoids to the mode of initiation and/or evolution of microangiopathy in diabetes mellitus, we measured serum lipid peroxides (LPO), an accepted index of intravascular free radicals, and plasma 11-dehydrothromboxane B2 (11-dehydro-TXB2), a stable metabolite of vasoactive thromboxane A2 released from platelets, in 95 patients with normolipidemic type 2 (non-insulin-dependent) diabetes mellitus at different stages of the disease. In general, either LPO or 11-dehydro-TXB2 was significantly greater in the patients, as a group, than in the matched controls (3.82 vs. 2.65 nmol/ml, P < 0.01 for LPO; and 17.3 vs. 5.8 pg/ml, P < 0.01 for 11-dehydro-TXB2). In patients, both LPO and 11-dehydro-TXB2 increased according to the severity of their diabetic retinopathy. A highly significant positive correlation existed between the LPO values and 11-dehydro-TXB2 in the patients (r = 0.64, P < 0.0001), while there was no such relationship in the controls (r = 0.18, P = NS). No difference in serum levels of apolipoproteins A-I, A-II, B, C-II, C-III, or E was observed between the patients and controls. Short-term glycemic control (25 cal/kg of standardized body weight/day, for 8 weeks) resulted in a small but significant reduction in LPO (4.2 vs. 4.6 nmol/ml, control; P < 0.05) without alteration in 11-dehydro-TXB2. There was a tendency towards deterioration in LPO according to the improvement in glycemic control. These results appear consistent with the view that, in addition to LPO, the release of TXA2 from activated platelet in the human circulation could be an important factor for the initiation and/or evolution of microangiopathy in diabetic patients even when they are not apparently hyperlipidemic. Further, the results of the present study emphasize the notion that more tight control of serum lipids is worthy of serious consideration in preventing the advance of diabetic microangiopathy.
Diabetes Res Clin Pract 1992 Nov
PMID:Possible relevance of lipid peroxidation and thromboxane production to the initiation and/or evolution of microangiopathy in non-hyperlipidemic type 2 diabetes mellitus. 147 57

It has been suggested that platelet hyperreactivity in patients with diabetes mellitus is associated with increased platelet production of thromboxane. We therefore compared the excretion of a thromboxane metabolite and platelet function in 50 patients with Type II diabetes mellitus who had normal renal function and clinical evidence of macrovascular disease and in 32 healthy controls. The mean (+/- SD) excretion rate of urinary 11-dehydro-thromboxane B2 was significantly higher in the patients than in the controls (5.94 +/- 3.68 vs. 1.50 +/- 0.79 nmol per day; P less than 0.001), irrespective of the type of macrovascular complication. Tight metabolic control achieved with insulin therapy reduced the levels of 11-dehydro-thromboxane B2 by approximately 50 percent. The fractional conversion of exogenous thromboxane B2 (infused at a rate of 4.5, 45.3, or 226.4 fmol per kilogram of body weight per second) to urinary 11-dehydro-thromboxane B2 was assessed in four patients, in whom it averaged 5.4 +/- 0.1 percent; this value did not differ from that measured in healthy subjects. Aspirin in low doses (50 mg per day for seven days) reduced urinary excretion of the metabolite by approximately 80 percent in four patients. The fact that thromboxane biosynthesis recovered over the following 10 days was consistent with a platelet origin of the urinary metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thromboxane biosynthesis and platelet function in type II diabetes mellitus. 234 67

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 effects of two anti-thrombotic and anti-lipidemic oils, evening primrose oil and fish oil, on glucose and lipid metabolism, prostaglandin (PG) levels and body composition were studied in patients with non-insulin-dependent diabetes. Seven patients were administered 4 g evening primrose oil, 2.4 g sardine oil and 200 mg vitamin E for 4 weeks. Fasting plasma glucose, hemoglobin A1c, total cholesterol, body weight and % body fat mass were significantly decreased after the treatment, and levels of changes in these parameters were not different from 11 patients who did not receive the oils. In the treatment group, concentrations of (e) icosapentaenoic acid (EPA) increased significantly in all the lipoprotein fractions, but dihomo-gamma-linolenic acid (DGLA) increased only in the high-density lipoprotein (HDL) fraction. The treatment decreased urinary 11-dehydro-thromboxane B2 excretion (32.7% decrease, P < 0.05), but did not alter significantly plasma PGE1 or 6-keto-PGF1 alpha levels. The ratio of 6-keto-PGF1 alpha and PGE1 to 11-dehydro-thromboxane B2 increased significantly after the treatment. These results suggest that these oil treatments are useful in improving abnormal lipid and thromboxane (TX)A2 metabolism in diabetic patients.
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PMID:Evening primrose oil and fish oil in non-insulin-dependent-diabetes. 841 6

To determine the pathogenic role of serotonin (5-HT), we investigated 5-HT metabolism in undergoing hemodialysis (HD). Mean value of platelet 5-HT in patients undergoing HD was significantly lower than that of normal controls (0.22 + or - 0.16 pmol/10(5) platelets versus 0.35 + or - 0.13 pmol/10(5) platelets, p <0.02). While platelet uptake of 5-HT in normal controls reached a plateau in each experiment after incubation with authentic 5-HT for 60 min, platelet uptake of 5-HT in patients undergoing HD reached various levels. We found significantly lower platelet 5-HT levels in patients with diabetes mellitus (DM) after HD compared with those in patients with chronic glomerulonephritis (p <0.05). The pathogenic role of serotonergic amplifying mechanism especially in patients with DM should be investigated. Second, we investigated plasma 11-dehydro-thromboxane B2 (11-DTXB2) levels in patients undergoing HD. Mean level of plasma 11-DTXB2 concentration in patients after HD was significantly higher than in patients before HD (32.8 + or - 17.0 pg/ml versus 23.7 + or - 7.2 pg/ml, p <0.02). Increased plasma levels of 11-DTXB2 after HD were regarded as an indication of hypercoagulation. Our results provide evidence that several factors such as hypercoagulation, heparin, 5-HT uptake of platelet, or causal diseases of renal failure could be responsible for the lower platelet 5-HT levels in patients undergoing HD.
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PMID:Serotonin metabolism in patients undergoing hemodialysis. 886

To evaluate platelet activity in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured the mean platelet volume (MPV) and 24-hour urinary excretion of 11-dehydro-thromboxane B2 (11-dTXB2) and 6-keto-prostaglandin F1 alpha (6-kPGF1 alpha), stable metabolites of thromboxane A2 and prostacyclin, respectively. The MPV of the 103 subjects in the NIDDM group were 10.72 +/- 0.82 fl for males and 10.52 +/- 1.01 fl for females (mean +/- SD), significantly higher than those of normal controls (9.95 +/- 0.75 fl for males and 9.84 +/- 0.72 fl for females). The MPV of patients with NIDDM showed positive correlations with fasting plasma glucose level and HbA1c (r = 0.234, P < 0.05; r = 0.267, P < 0.01, respectively). The urinary excretion of 11-dTXB2 was greater in the NIDDM group (7.58 +/- 4.42 micrograms/day for males and 5.65 +/- 2.38 micrograms/day for females) than in the normal controls (4.61 +/- 2.31 and 3.83 +/- 1.60, respectively), suggesting that the synthesis of thromboxane A2 by platelets may be accelerated in vivo in patients with NIDDM. The urinary 6-kPGF1 alpha was not different between the NIDDM group and normal controls among the males, but was greater in the NIDDM group among the females. As MPV showed a positive correlation (r = 0.364, P < 0.05) with urinary excretion of 11-dTXB2, MPV may be related to platelet activity. These findings suggest that the platelets of patients with NIDDM may be in a hyperactive state.
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PMID:Platelet volume and urinary prostanoid metabolites in non-insulin-dependent diabetes mellitus. 922 78

We describe variations of 11-dehydrothromboxane B2(11-dehydro-TXB2) levels in human urine samples. Retinal vein occlusion (RVO) is a thrombotic disease in which the retinal vein is blocked by blood aggregations. We considered the possibility that 11-dehydro-TXB2 plays an important role in the formation of RVO. Thus, we determined the 11-dehydro-TXB2 levels in patients with RVO using gas chromatography/selected ion monitoring (GC/SIM) and compared them with those of healthy volunteers. The thromboxane levels in patients with RVO, who did not also have diabetes, were significantly higher than those in healthy volunteers. One cause of RVO may be the variation of thromboxane production. Furthermore, this GC/SIM method can be applied to the prevention and treatment of not only RVO, but also of general thrombosis.
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PMID:Analysis of urinary 11-dehydrothromboxane B2 in patients with occluded retinal vein using GC/SIM. 948 68

We established microdetermination methods of prostaglandin (PG) metabolites by GC-selected ion monitoring (GC-SIM) and applied them to the clinical investigations. At first the microdetermination of delta 17-6-keto-PGF1 alpha, a hydrolyzed metabolite of PGI2, is described. An authentic delta 17-6-keto-PGF1 alpha was prepared from eicosapentaenoic acid (EPA) incubated with a homogenate from the bovine aortic intima. [18O] delta 17-6-Keto-PGF1 alpha was synthesized to obtain an internal standard for GC-SIM of delta 17-6-keto-PGF1 alpha. A good linear response over the range of 10 pg-5 ng was demonstrated. Chromatographic conditions using a MP-65HT column presented nearly baseline separation of delta 17-6-keto-PGF1 alpha and 6-keto-PGF1 alpha. Furthermore, a monoclonal antibody against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate delta 17-6-keto-PGF1 alpha in the human blood sera. Using the prepared immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly detected in the human blood sera by GC/MS analysis. We were able to detect delta 17-6-keto-PGF1 alpha of the amount ranging from 6 to 26 pg/ml in the human blood plasma. The present method can be applied to the determination of delta 17-6-keto-PGF1 alpha in the human urine and plasma. Diabetes mellitus induces platelet alterations such as hyperaggregation. Variations in PG production seem to be related to this phenomenon but the changes in PG levels remain unclear. So we microanalyzed the 11-dehydrothromboxane B2 (TXB2) and 2,3-dinor-6-keto-PGF1 alpha, which were stable metabolites of TXA2 and PGI2, in the urine and investigated the relationship between the thromboxane/prostacyclin (TX/PGI) ratio and diabetes mellitus. The TX/PGI ratio in the urine of diabetics was higher than that of healthy volunteers. In murine, the TX/PGI ratio of STZ-induced mice was also higher than that of non-induced mice. The ratio of db/db mice also increased with the progress of diabetes mellitus. Furthermore, we investigated the relationship between the retinal vein occlusion (RVO), a thrombotic disease in which the retinal vein is blocked by blood aggregations, and the TX/PGI ratio. The TX/PGI level in patients with the RVO, who were not combine diabetes, was significantly higher than that in healthy volunteers. One of the causes of the RVO may be due to the variation of thromboxane production. This GC-SIM method can be used to determine the TX/PGI ratio in the urine.
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PMID:[Establishment of microanalysis of prostaglandin metabolites by GC/MS and its clinical application]. 992 10

Levels of the stable urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 2,3-dinor-6-keto-prostaglandin F1alpha (2,3-dinor-6-keto-PGF1alpha) were measured in diabetics to elucidate the relation between the thromboxane A2/prostacyclin (TX/PGI) balance and pathological states of diabetes mellitus. 11-Dehydro-TXB2 and 2,3-dinor-6-keto-PGF1alpha were derivatized to methyl ester-propylamide-dimethylisopropylsilyl ether and methyl ester-methoxime-dimethylisopropylsilyl ether derivatives, respectively, and applied to a gas chromatography/selected ion monitoring. The TX/PGI ratios of diabetics were higher than those of healthy volunteers, suggesting the hypercoagulative states of this disease. The ratios showed positive correlations with the levels of blood glucose. The levels of hemoglobin A1c and triglyceride were correlated weakly with the ratio. Some of the patients who had relatively low levels of blood glucose also showed high TX/PGI ratios. Furthermore, the ratio increased in the order of the groups 1, 2, and 3; group 1 contained patients who did not take medicine for diabetes, group 2 contained those who took oral hypoglycemic agents, and group 3 contained those who received insulin therapy. These observations indicate that the TX/PGI ratio reflects the pathological conditions of diabetes and is a useful marker, having few different features from other markers that are presently used.
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PMID:Urinary thromboxane A2/prostacyclin balance reflects the pathological state of a diabetic. 1059 68

Cerebrovascular disease and other vascular diseases are common complications of non-insulin-dependent diabetes mellitus (NIDDM) and are associated with its increased morbidity and mortality. Platelet activation plays an important role in the pathomechanisms of these vascular diseases. Although several indices have been used to assess platelet activation, few data are available indicating which are more sensitive or more valuable in this situation. We have measured platelet arachidonic acid metabolites [thromboxane B2 (TXB2) and 11-dehydro-thromboxane B2 (TXB2)] and plasma P-selectin, platelet fibrinogen binding and membrane glycoproteins in 47 well-characterized NIDDM patients with cerebrovascular disease, 38 NIDDM patients without vascular diseases, and 36 age-matched healthy individuals. Our study shows that platelets were remarkably activated in NIDDM patients with cerebrovascular diseases. The measurement of plasma 11-dehydro-TXB2 and the determination of fibrinogen binding to, and P-selectin expression on platelets would reveal a higher diagnostic sensitivity for detecting in vivo platelet activation than other markers.
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PMID:Comparative study of platelet activation markers in diabetes mellitus patients complicated by cerebrovascular disease. 1168 40


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