Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Progetto Lombardo Atero-Trombosi (PLAT) Study was a prospective, multicenter, multidisciplinary study of the association among hemostatic variables, conventional risk factors, and atherothrombotic events in four groups of patients with preexisting vascular ischemic disease (335 myocardial infarction survivors, 123 patients with stable angina pectoris, 160 with transient ischemic attacks, and 335 with peripheral vascular disease). In the myocardial infarction group, univariate analysis showed that atherothrombotic events were associated with high fibrinogen (p = 0.001), factor VIII:C (p less than 0.001), and von Willebrand factor antigen (vWF:Ag) (p = 0.004) levels and with low high density lipoprotein cholesterol (p = 0.043), factor VII (p = 0.019), and protein C (p = 0.044) levels; multivariate analysis produced associations with high fibrinogen and factor VIII:C levels and low protein C levels. By both univariate and multivariate analysis, events in the angina pectoris group were associated with high vWF:Ag (p = 0.026) and leukocyte (p = 0.033) levels and the presence of carotid arterial stenosis (p = 0.063); associations with high leukocyte (p = 0.037) and factor VIII:C (p = 0.186) levels, family history (p = 0.031), and diabetes (p = 0.061) were also found in the group with transient ischemic attacks. In those with peripheral vascular disease, events were associated with Fontaine stage greater than or equal to IIB (p = 0.024), high factor VIII:C levels (p = 0.073), and low protein C (p = 0.028), fibrinogen (p = 0.030), antithrombin III (p = 0.054), and factor VII (p = 0.057) levels by univariate analysis and with Fontaine stage and low fibrinogen levels by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. PLAT Study Group. Progetto Lombardo Atero-Trombosi (PLAT) Study Group. 152 21

Endothelial cells form the luminal vascular surface and thus have a central role in the regulation of coagulation. One important way in which endothelial cells control the clotting system is by regulating the expression of binding sites for anticoagulant and procoagulant factors on the cell surface. In the quiescent state, endothelial cells maintain blood fluidity by promoting the activity of numerous anticoagulant pathways, including the protein C/protein S pathway. After activation, as can be brought about by cytokines, the balance of endothelial properties can be tipped to favor clot formation through coordinated induction of procoagulant and suppression of anticoagulant mechanisms. Tumor necrosis factor suppresses the endothelial anticoagulant cofactor thrombomodulin and induces expression of the procoagulant cofactor tissue factor. Working in concert, these changes can allow fibrin formation to proceed in an inflamed focus but maintain blood fluidity in the surrounding area of normal vasculature. Recent studies suggest that similar changes in endothelial coagulant properties can be induced by advanced glycosylation end products, proteins modified by glucose that accumulate in the vasculature at a rapid rate in diabetic subjects, indicating the potential relevance of these mechanisms in diabetic vascular disease.
Diabetes Care 1991 Feb
PMID:Endothelium and regulation of coagulation. 206 Apr 25

Thrombomodulin (TM) is a membrane protein in the vascular endothelium, and it plays an important role as a cofactor in the thrombin-catalyzed activation of protein C. It has also been found in human plasma; however, its clinical significance is not known. In this study, fasting plasma TM concentrations in 67 diabetic patients with different degrees of albuminuria (39 men aged 57 +/- 8 yr, 28 women aged 57 +/- 11 yr; means +/- SD) and 34 age- and sex-matched healthy subjects were investigated by use of a one-step sandwich enzyme immunoassay, a new method developed by H.I. and others. As a screening, the patients were divided into three groups according to the first morning urinary concentrations of albumin: group 1, less than 30 micrograms/ml (normoalbuminuria); group 2, 30-140 micrograms/ml (microalbuminuria); group 3, greater than 140 micrograms/ml (clinical nephropathy). There was no significant difference in plasma TM level between the control group (17.7 +/- 3.7 ng/ml, n = 34) and group 1 (16.9 +/- 3.4 ng/ml, n = 30); however, plasma TM concentrations in group 2 (22.8 +/- 3.4 ng/ml, n = 22) and group 3 (29.6 +/- 6.1 ng/ml, n = 15) increased significantly compared with those in the control group and group 1, respectively. As a further investigation, three timed overnight urine collections were made. The patients were allocated to three groups according to their rates of albumin excretion: group I, less than 20 micrograms/min (normoalbuminuria); group II, 20-200 micrograms/min (microalbuminuria); group III greater than 200 micrograms/min (clinical nephropathy).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Aug
PMID:Elevation of plasma thrombomodulin level in diabetic patients with early diabetic nephropathy. 216 5

Effects of streptozotocin-induced diabetes and administration of the insulinmimetic agent, vanadate in rats on the liver protein kinase C-induced phosphorylation of exogenous C (Histone III-S) and endogenous substrates were investigated. Diabetes caused a significant fall (40-60%) in liver cytosolic protein C activity measured using both types of substrates. Vanadate treatment for a period of 5 weeks restored them to normal levels. Phosphorylation of cytosolic target proteins for protein kinase C followed a similar pattern in response to diabetes and vanadate. These treatments had no effect on particulate protein kinase C activity. Vanadate also had no effect in normal livers with respect to the protein kinase C system.
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PMID:Decrease of liver protein kinase C in streptozotocin-induced diabetic rats and restoration by vanadate treatment. 224 91

Plasma levels of protein S (PS) antigen, both total and free fractions, were measured together with C4b-binding protein (C4bp) and protein C (PC) antigen in 39 patients with disseminated intravascular coagulation (DIC), 34 with liver disease, 17 with collagen disease, 17 with diabetes mellitus, and 51 under stabilized warfarin treatment. In patients with DIC, mean concentrations of total PS and free PS were normal, while PC was reduced and C4bp were elevated. Total PS, free PS, C4bp and PC were all decreased in liver disease, elevated in diabetes mellitus, and normal in collagen disease. In warfarin-treated patients, total PS, free PS and PC were moderately decreased, but the decrease in C4bp was minimal. The concentration of PS correlated positively with PC in liver disease, diabetes mellitus, and during oral anticoagulation, but did not in DIC. These results indicate that PS and PC behave similarly when liver synthetic function is principally affected, but in contrast to PC, PS is hardly consumed during intravascular coagulation.
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PMID:Plasma protein S in disseminated intravascular coagulation, liver disease, collagen disease, diabetes mellitus, and under oral anticoagulant therapy. 252 31

The present prospective follow-up study was made to study the effect of glycaemic regulation on levels of factor VII, protein C and protein S in 15 insulin-dependent diabetic patients without manifestations of vascular disease. Patients were tested before and after 8 weeks of 'metabolic' intervention, whereby a near-normoglycaemic state was achieved. At baseline, values of cross-linked fibrin degradation products (XL-FDP) and levels of 'total' protein S were significantly increased and protein C values were decreased in the diabetic patients when compared to control subjects, whereas levels of factor VII and 'free' protein S were near normal. After 'metabolic' intervention a decrease of all haemostatic parameters were recorded, however XL-FDP levels did not decline to control levels and the imbalance of factor VII and protein C persisted. When patients with newly diagnosed diabetes (n = 8) were compared to those with long-term disease (n = 7) higher levels of factor VII, protein C and protein S were recorded in the latter group before and after metabolic intervention; at baseline the differences reached statistical significance for factor VII and protein S, and remained significant for factor VII after metabolic intervention. Before and after intervention XL-FDP levels were higher in patients with newly diagnosed disease than in patients with long-term diabetes. The correlation analysis revealed positive correlations of factor VII, protein C and protein S to cholesterol and triglycerides, of protein S to all glycaemic control parameters, negative correlations of protein C to glucose, and of XL-FDP to factor VII, protein C and protein S. The results indicate an imbalance of haemostasis towards thrombophilicity in insulin-dependent diabetic patients, not completely correctable by glycaemic control.
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PMID:The effect of near-normoglycaemic control on plasma levels of coagulation factor VII and the anticoagulant proteins C and S in insulin-dependent diabetic patients. 253 36

The plasma levels of protein C were investigated in 54 type I diabetic patients without retinopathy and in 14 diabetic patients with diabetic retinopathy and compared with the findings in 35 sex- and age-matched healthy control subjects. In the total group of type I diabetic patients, protein C was significantly less than in the controls. The lowest levels of protein C were found in diabetic patients with the poorest metabolic control. Protein C levels showed a significant negative correlation with the blood glucose levels, but they were not correlated with hemoglobin A1c (HbA1c). Although patients with retinopathy showed the least decrease of the plasma level of protein C among the diabetic subjects, the ratio of protein C to factor II was significantly decreased compared with the control subjects. Because the levels of coagulation factor II were not reduced in diabetic patients, the reduction of protein C seems to be caused, not by reduced synthesis in the liver, but more likely by an increased clearance from the blood plasma. The decrease of protein C in the plasma of type I diabetic patients indicates an abnormal, probably hypercoagulable, hemostatic situation in this disorder.
Diabetes 1986 May
PMID:Decreased protein C levels in patients with insulin-dependent type I diabetes mellitus. 375 29

Microalbuminuria in diabetic patients is associated with an increased cardiovascular risk which is not completely explained by an excess of conventional cardiovascular risk factors. A depression of physiologic inhibitors of blood coagulation could contribute to a thrombophilic state and to cardiovascular complications: data on protein C in diabetic patients are controversial, and no information exists about protein C activity in non-insulin-dependent diabetic patients or its relation to the microalbuminuric state. The aim of this study was to assess protein C activity in non-insulin-dependent diabetic patients with and without microalbuminuria. Protein C activity was determined (Protein C Reagent, Boehringer Mannheim, Germany) in 29 non-insulin-dependent diabetic patients with microalbuminuria (group A, > 20 micrograms/min), 33 non-insulin-dependent diabetic patients with normoalbuminuria (group B), and in 36 non-diabetic healthy blood donors as a control group (group C). The groups were matched for sex, and no difference in age, body mass index, blood pressure, glycated haemoglobin or known duration of diabetes was observed between groups A and B. Protein C activity was similar in the three groups (mean +/- SD): group A, 106.9% +/- 25.2%; group B, 109.3% +/- 27.6%; group C, 103.1% +/- 18.9%; F value 0.58, NS. Protein C activity did not correlate significantly with body mass index, glycated haemoglobin, known duration of diabetes, age or albumin excretion rate in any of the groups or in the diabetic patients as a whole. No significant difference in protein C activity was observed in patients taking other therapy (diet, oral agents, insulin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticoagulant protein C activity in non-insulin-dependent diabetic patients with normoalbuminuria and microalbuminuria. 757 30

Anticoagulant response to activated protein C (APC) was studied in 40 healthy subjects and 67 patients with insulin-dependent diabetes mellitus (IDDM) using a modified activated thromboplastin time assay. Results are expressed in terms of the APC sensitivity ratio (APC SR). In addition, plasma levels of protein C, total and free protein S (PS), coagulation factors V and VIII, and prothrombin fragment 1+2 (F1+2) were measured. Patients with IDDM and a urinary albumin excretion rate (UAER) < 30 mg/24 h showed a median APC SR of 2.5 (interquartile range 2.3-2.9). In patients with a UAER between 30 and 300 mg/24 h, the median APC SR was 2.7 (2.7-2.9). Both values were significantly greater than the median APC SR of 2.1 (2.0-2.5) observed in healthy control subjects (P < 0.001). Also, the percentage of subjects with an APC SR < or = 2.0 was markedly smaller in both patient groups. Factor V and VIII levels were not significantly different between IDDM patients and healthy subjects. Grouping of IDDM patients according to the APC SR revealed significantly enhanced levels of total PS (P < 0.05) and factor VIII (P < 0.01) in patients with a poor anticoagulant response to APC (APC SR < or = 2.0) compared with those with an APC SR > 2.7. The negative correlation of the APC SR in diabetic patients with both coagulation and anticoagulation factors indicates a complex role of this parameter in regulating the coagulation system in IDDM.
Diabetes 1995 Sep
PMID:Enhanced anticoagulant response to activated protein C in patients with IDDM. 765 25

Recent cohort and case control studies of low-dose combined oral contraceptives (COCs) containing the new generation of progestogens have allowed classification of adverse effects into those which are rare but serious and should be considered risks and those which are more frequent but are less of a threat to health. Low-dose COCs continue to affect coagulation in a complex way, but the risk is less than with the older preparations, and it can be minimized by screening women for a personal or familial history of early or unusual thrombosis and for levels of protein C, S, and antithrombin III. Women with true migraine with focal signs should also avoid using COCs. The relative risk of myocardial infarction (MI) may increase from 4:1 in women with one risk factor (age, smoking, hypertension, hyperlipidemia, and diabetes) to 20:1 with two risk factors and 128:1 with three or more risk factors. In the absence of all risk factors, a recent study indicated that the relative risk of MI with COC use was 1.9 for current and past use. COC use also causes a slight increase in hypertension in most women, especially those who are older or have a family history of hypertension. While the COC can affect carbohydrate and lipid metabolism, the new generation of progestogens has reduced these effects. The COC may accelerate presentation of gallbladder disease in predisposed women. The COC protects against benign breast disease but may increase the risk of breast cancer and cervical cancer slightly. There is a strong link between hepatocellular adenoma and COC use, but the incidence is low. Return to fertility after use has not been a problem. Both estrogenic adverse effects (nausea, dizziness, irritability, weight gain, bloating) and progestogenic adverse effects (vaginal dryness, acne, hirsutism, weight gain, depression, loss of libido) can occur in 50% of women, but these generally disappear after a few months of use. In conclusion, the low-dose, third generation COCs are associated with minimal risks in the absence of other risk factors and have many beneficial effects such as the prevention of ovarian and endometrial cancer; a decrease in pelvic inflammatory disease and ectopic pregnancies; and protection from anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease as well as from the morbidity and mortality associated with pregnancy.
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PMID:The combined oral contraceptive. Risks and adverse effects in perspective. 776 40


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