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

Alterations of coagulation and fibrinolytic systems might contribute to the increased cardiovascular and cerebrovascular mortality observed in patients with both chronic growth hormone (GH) excess (acromegaly) and deficiency (GHD). However, contrasting results have been so far reported. To assess the importance of GH in modulating haemostatic system, several haemostatic variables in patients with GHD and acromegaly were measured. Twenty-four adult patients with GHD (8 childhood- and 16 adult-onset; age: 41+/-12 years, insulin like growth factor-I, IGF-I: 6.7+/-4 nmol/L), 10 non-diabetic acromegalic patients (age: 39+/-15 years; IGF-I: 109+/-37 nmol/L) and 64 healthy volunteers age- and sex-matched with cases were studied. The plasma levels of tissue-type plasminogen activator antigen (t-PA), prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were measured by ELISA. Plasminogen activator inhibitor type I (PAI-1) was measured by an immunoactivity assay and fibrinogen by von Clauss method. GH levels were measured by IFMA and IGF-I by RIA. GHD patients had higher PAI-1 (12.7+/-16.7 vs 4.8+/-5.3 U/ml, p<0.01), fibrinogen (363+/-104 vs 291+/-71 mg/dL, p< 0.05) and TAT levels (6.8+/-9 vs 3.6+/-2.8 ng/ml, p<0.05) than controls. Taking the 95th pecentile of the normal distribution in the control group as the cut-off point for normal plasma levels of the haemostatic variables, high PAI levels were found in 25% of patients with GHD (P<0.01), while high fibrinogen and TAT levels were observed in 21% (P<0.05). The alterations were mostly present in patients with adult-onset GHD, with the exception of hyperfibrinogenaemia which was equally present in adult- and childhood-onset patients. Acromegalic patients had higher mean fibrinogen levels than controls (398+/-111 vs 291+/-71 mg/dL, p< 0.05), 40% having hyperfibrinogenaemia (P<0.01, vs controls). They also had t-PA levels lower than controls and GHD. No correlations between hormonal and haemostatic variables were found. Body mass index and waist to hip ratio correlated positively with PAI-1 levels in GHD patients only. In conclusion, this study shows that several abnormalities of coagulation variables (increased PAI-1. fibrinogen and TAT levels) are present in patients with GHD, while only hyperfibrinogenaemia is found in patients with acromegaly. These changes do not appear to be directly related to IGF-I levels or to the degree of GH deficiency/excess. However, these abnormalities may be an additional trigger for the development of coronary heart disease and thromboembolic complications mostly in patients with GHD.
Exp Clin Endocrinol Diabetes 2000
PMID:Alterations of haemostatic and fibrinolytic markers in adult patients with growth hormone deficiency and with acromegaly. 1108 70

A 67-year-old woman with diabetes mellitus was hospitalized due to a throbbing headache. She appeared neurologically normal, except for meningeal irritation. The cerebrospinal fluid pressure was high. There was increased fluid protein without an increased cell count. Brain CT scan showed no abnormality, however, brain magnetic resonance angiography (MRA) showed complete right transverse sinus stasis and partial left transverse sinus stasis, indicating bilateral transverse sinus thrombosis. At this time thrombin anti-thrombin III complex (TAT) and prothrombin fragment F1+2 (PTF1+2) indicating hypercoagulation had increased. Urokinase, followed by aspirin and ticlopidine hydrochloride were administered. After diet therapy and transient insulin administration, her blood glucose levels improved. By the 22nd day, the headache had disappeared. Subsequently, brain MRA showed left transverse sinus blood flow recovery and complete right transverse sinus stasis, while carotid angiography showed recovered left transverse sinus but right transverse sinus defect. TAT and PTF1+2 levels improved concomitantly with better blood glucose control. We diagnosed this case as left transverse sinus thrombosis because of the hypercoagulable state resulting from diabetes mellitus accompanied by right transverse sinus aplasia.
Diabetes Res Clin Pract 2001 Jan
PMID:Diabetes mellitus with left transverse sinus thrombosis and right transverse sinus aplasia. 1113 80

Eighty percent of patients with diabetes mellitus die a thrombotic death. Seventy-five percent of these deaths is due to cardiovascular complications, and the remainder is due to cerebrovascular events and peripheral vascular complications. Vascular endothelium, the primary defense against thrombosis, is abnormal in diabetes. Endothelial abnormalities undoubtedly play a role in the enhanced activation of platelets and clotting factors seen in diabetes. Coagulation activation markers, such as prothrombin activation fragment 1+2 and thrombin-anti-thrombin complexes, are elevated in diabetes. The plasma levels of many clotting factors including fibrinogen, factor VII, factor VIII, factor XI, factor XII, kallikrein, and von Willebrand factor are elevated in diabetes. Conversely, the level of the anticoagulant protein C (PC) is decreased. The fibrinolytic system, the primary means of removing clots, is relatively inhibited in diabetes due to abnormal clot structures that are more resistant to degradation and an increase in plasminogen activator inhibitor type 1 (PAI-1). Increased circulating platelet aggregates, increased platelet aggregation in response to platelet agonists, increased platelet contractile force (PCF), and the presence of higher plasma levels of platelet release products, such as beta-thromboglobulin, platelet factor 4, and thromboxane B(2), demonstrate platelet hyperactivity in diabetes. This constellation of findings supports the clinical observation that diabetes is a hypercoagulable state. This article briefly reviews the published evidence for this conclusion and the putative roles played by hyperglycemia and hyperinsulinemia in its development.
J Diabetes Complications
PMID:Diabetes mellitus: a hypercoagulable state. 1125 26

The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.
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PMID:The use of silymarin in the treatment of liver diseases. 1173 32

Prothrombin is a key factor in blood clotting, a process intimately involved in thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case-control study within the Cardiovascular Health Study. Cases included angina, myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n approximately 250 each). Population-based controls free of clinical cardiovascular disease (CVD) (n approximately 500) and a subset free of clinical and subclinical CVD (n approximately 250) were used for comparison. The 20210 A allele, frequency 2.9%, was associated with higher mean prothrombin levels: 166.3 vs. 139.5 microg/ml (P <0.001). Significant correlates of prothrombin included gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory markers, but not race, smoking, hypertension, diabetes, measures of subclinical CVD, or markers of procoagulant activity. Compared to controls, neither genotype nor prothrombin level was associated with any CVD case group. We conclude that, in the elderly, neither prothrombin level nor 20210 genotype were associated with either CVD risk factors or events. This is consistent with the lack of association of prothrombin levels with measures of underlying CVD or procoagulant markers.
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PMID:No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. 1200 43

We describe a patient with Fanconi-Bickel syndrome diagnosed by clinical manifestations and the identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed with neonatal diabetes mellitus due to hyperglycaemia and glycosuria at 3 days of life. In addition, newborn screening for galactosaemia revealed hypergalactosaemia. Thereafter, she was managed with lactose-free milk and insulin therapy. However, she failed to grow and her liver became progressively enlarged. Her liver function deteriorated with increased prothrombin time. A liver biopsy done at age 9 months showed micronodular cirrhosis with marked fatty changes and she succumbed to hepatic failure with pneumonia at 10 months of age. DNA sequencing analysis of the GLUT 2 gene using her genomic DNA revealed a novel mutation in codon 5, lysine5 stop(K5X).
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PMID:Identification of a novel mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome presenting with neonatal diabetes mellitus and galactosaemia. 1202 58

To investigate the surgical results of hepatectomy for hepatocellular carcinoma in relation to hepatitis virus status in Taiwan, 252 patients (196 men and 56 women; March 1992 to August 1998) were reviewed. The patients were divided into four groups: 30 patients (11.9%) seronegative for both hepatitis B surface antigen (HBsAg) and antihepatitis C antibody (HCVAb) (N-HCC group); 133 patients (52.8%) seropositive for HBsAg and seronegative for HCVAb (B-HCC group); 66 patients (26.2%) seronegative for HBsAg and seropositive for HCVAb (C-HCC group); and 23 patients (9.1%) seropositive for both HBsAg and HCVAb (BC-HCC group). Patients in group C-HCC were older (p = 0.001) and had a higher incidence of diabetes mellitus (p = 0.004). Also, they had a higher indocyanine green retention rate at 15 minutes (p = 0.021), longer international normalization ratio for the prothrombin time (p = 0.049), and smaller tumor (p = 0.006). Postoperative complications and hospital mortality were significantly higher in patients in the C-HCC and BC-HCC groups (p = 0.046, 0.021). All patients were followed 12 to 76 months after hepatectomy (mean 23.5 +/- 16.3 months). The 1-, 3-, and 5-year overall cumulative survival rates of the 252 patients in this series were 80%, 54.3%, and 34.2%, respectively. The cumulative intrahepatic recurrence rates were 46.5%, 64.9%, and 72.9% at 1, 3, and 5 years, respectively. The mean disease-free survival time was longest in group C-HCC and shortest in group BC-HCC (p = 0.020). The overall survival time and cumulative survival rates in the four groups were not significantly different (p = 0.146).
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PMID:Surgical results in patients with hepatitis virus-related hepatocellular carcinoma in Taiwan. 1205 31

Possible hepatic effects of oral contraceptives (OCs) include tumors, intrahepatic cholestasis, and less well known vascular lesions such as Budd-Chiari syndrome and peliosis, a disseminated pseudocystic dilatation of the sinusoid capillaries of the liver. A 29-year-old woman with a history of 4 pregnancies, hypertension and diabetes both requiring daily medication, and use since April 1983 of an oral contraceptive (OC) containing .15 mg levonorgestrel and .03 mg of ethinyl estradiol complained in March 1984 of epigastric pain and increased abdominal volume. Ascitis was diagnosed and the patient was hospitalized. She had experienced a generalized pruritus for several months and had lost weight. The bilirubin, alcaline phosphatase, and Gamma GT levels were slightly elevated. Sonography showed a hypertrophied liver. Incipient esophageal varices were seen with gastric fibroscopy. The small subhepatic venous branches had a cloudy aspect. The peliosis hepatis was diagnosed by a transjugular puncture biopsy of the liver. With discontinuation of the OCs, the ascites did not reappear after puncture and the perturbations of the liver functioning normalized. On follow-up in April 1985, slight hepatomagaly persisted but the patient reported no further symptoms. She continued her medication for hypertension and diabetes. Peliosis hepatis was 1st described in 1964 and several cases related to OC use have been reported since 1972. Peliosis has the aspect of multiple small congestive cavities of 1-3 mm in diameter in the parenchyma. The lesions consist of areas of hepatocellular necrosis secondarily filled with blood. The cysts may be voluminous and subcortical, creating a risk of hemoperitoneum. The lesions may also be associated with a benign or malignant liver tumor. Regression of the lesions is possible with termination of the etiologic agent. Clinically, hepatomegaly, painful or not, sometimes associated with splenomegaly, is often found with peliosis. Moderate jaundice is very frequent. Ascites or edema of the legs are observed. Hyperbilirubinemia and augmentation of phosphatases and Gamma GT are the main laboratory findings. Transaminases may be slightly elevated, and the rate of prothrombin may be diminished. The condition is sometimes diagnosed with laparoscopy, celiomesenteric arteriography, or phlebography, but hepatic puncture biopsy usually establishes the diagnosis. The contition may improve if the etiologic agent is removed or it may worsen because of liver failure or a complication such as hemoperitoneum or an associated tumor.
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PMID:[Peliosis hepatis and oral contraceptives: a case report]. 1228 Oct 5

The clinical course of a term neonate (birthweight 3.14 kg) who developed thrombosis of the left common and internal iliac veins on day 21 following recovery from Streptococcus mitis septicemia, with shock diagnosed on day 13, is reported. Subcutaneous low molecular weight heparin (LMWH) was commenced (1.5 mg/kg 12 hourly for 10 days) after 13 h of standard heparin infusion, due to difficulties in securing a peripheral venous access. The inflammation of the left leg was completely resolved by day 5 of LMWH therapy. Prothrombin time, activated prothrombin time and fibrinogen levels were within normal limits during LMWH therapy. Treatment-related side effects, such as thrombocytopenia and bleeding tendency were not noted. Doppler studies 6 weeks after discharge home on day 33 revealed complete resolution of the thrombus. Apart from septicaemia and shock, the presence of an indwelling central venous catheter and a history of untreated maternal diabetes were additional risk factors for thrombosis. Because it is as effective as standard heparin, LMWH may be a therapeutic option for thrombosis in high-risk neonates, particularly given its ease of administration by the subcutaneous route, predictable pharmacokinetics and reduced incidence of adverse effects such as bleeding complications.
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PMID:Low molecular weight heparin for neonatal thrombosis. 1241 Aug 80

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2 to approximately 4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F(1+2) levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.
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PMID:Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women. 1243 Aug 99


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