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)

Diabetic patients have increased morbidity and mortality attributable to myocardial infarction, cerebrovascular disease and peripheral vascular disease, due to a high incidence of premature atherosclerosis. Abnormalities of hemostasis have been reported in many studies on diabetes over almost thirty years, but unfortunately the results have often appeared contradictory. The hemostatic alterations could lead to increased risk of vascular disease in diabetic patients. We have studied some coagulation factors (Fibrinogen, Factor II, Factor VII) and coagulation inhibitors (Protein C, Protein S), and plasminogen in fifty-four type 2 diabetic patients. The possible relationship between coagulation factors and coagulation inhibitors and parameters for glyco-metabolic control (glycosylated hemoglobin, fructosamine) and disturbed lipid metabolism (cholesterol, triglycerides) have ben analyzed. Our results show increase of fibrinogen, correlated with the metabolic control of the disease, positive correlation between plasminogen, factor II, protein S and hypertriglycerides, decreased levels of protein C correlated neither with metabolic control of disease neither with disturbed lipid metabolism.
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PMID:[Evaluation of the coagulation and fibrinolysis system in 54 patients with type 2 diabetes mellitus: correlations with lipid metabolism and blood glucose control]. 876 54

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 +/- 3.8 vs 3.0 +/- 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 +/- 2.6 vs 35.3 +/- 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 +/- 0.6 vs 8.6 +/- 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 +/- 2.9 vs 23.4 +/- 2.6%, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.
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PMID:Protein C activation in NIDDM patients. 896 Aug 26

In nonobese diabetic mice, autoimmune diabetes progresses in an age-linked and gender-dependent manner. Insulitis begins in male and female mice at approximately 1 mo of age; however, 70 to 90% of females, but only 10 to 20% of males, become diabetic by 6 mo. Multiple studies propose that proinflammatory Th1 and immunomodulatory Th2 cytokines impact diabetes pathogenesis, but the role of these cytokines in spontaneous diabetes progression is not yet clear. We used quantitative reverse-transcriptase-coupled PCR to analyze expression of cytokines and APC costimulatory molecules in the islets of 20- to 180-day-old male and female nonobese diabetic littermates, and identified three stages in diabetes progression. At 1 to 2 mo of age, islet-infiltrating T cells displayed a Th1 cytokine bias in females, and a Th2 cytokine bias in males. In females, stage II (2-3 mo of age) was characterized by an increase in islet-infiltrating T cells, APC, and Th1 cytokines, whereas male infiltrates did not increase in size, and Th1 cytokine expression continued to decline during this interval. Islet infiltration reached a plateau (stage III) in 3- to 4-mo-old females, months before overt diabetes onset. Our data imply that Th cytokine expression in early insulitis exerts substantial impact on beta cell destruction and overt diabetes. A clinical implication of our results is that young individuals in the early stages of insulitis are ideal candidates for therapeutic intervention to minimize beta cell destruction and morbidity.
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PMID:IL-4 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice. 903 92

Type 1 (insulin-dependent) diabetes mellitus is associated with long-term vascular complications. In addition to metabolic factors, immunological and haemostatic mechanisms may be involved. Lupus anticoagulant (LA), an immunoglobulin which interferes with endothelial cell function, is frequently associated with a high risk of thromboembolic events. LA has been described in several diseases but never in diabetes mellitus. The aim of this study was to evaluate if endothelial dysfunction and unmodulated haemostasis are amplified by the presence of LA in Type 1 diabetic patients. Plasma samples collected from clinically and biochemically well-characterized Type 1 diabetic patients were examined for LA, fibrinogen, prothrombin (PT), PTT, prothrombin degradation products (F1 + 2) and activated protein C (APC). The results revealed significantly decreased APC and increased F1 + 2 plasma concentrations in LA-positive but not in LA-negative patients; 60% of LA-positive and only 18% of LA-negative patients had microangiopathy (not significant). No thrombotic episodes in large vessels were found in LA-positive patients. These findings suggest that LA could be considered an additional factor in the onset and/or progression of diabetic complications, acting as a link between the immunological and haemostatic systems in the pathogenesis of diabetic microangiopathy.
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PMID:Diabetic microangiopathy: lupus anticoagulant dependent thrombotic tendency in type 1 (insulin-dependent) diabetes mellitus. 904 90

The acute phase reaction is a molecular response to noxious stimuli. Over 50 glycoproteins have been identified as reactants. While this is likely a protective response, some of the changes could be detrimental to body homeostasis. The objective of this study was to examine whether an acute phase reaction occurs in diabetic patients with foot ulcers. In age- and sex-matched populations, measurements of C-reactive protein, fibrinogen, albumin, hematocrit, whole blood viscosity and protein C were performed on: (i) 24 diabetic patients with a foot ulcer (group A); (ii) eight diabetic patients without foot ulcer (group B); and (iii) seven patients without diabetes (group C). Analysis of variance was used to compare means of each respective group (mean (s.d.)). Group A demonstrated an increase in C-reactive protein (5.6 (5.4) mg/dl) compared with group B (0.78 (0.46) mg/dl; P = 0.013) and group C (0.71 (0.26) mg/dl; P = 0.026). Fibrinogen was also increased in group A (619 (205) mg/dl) compared with group B (310 (58) mg/dl; P = 0.005) and group C (370 (88) mg/dl; P = 0.04). Hematocrit (37 (6)%) and albumin (3.5 (0.5) g/dl) were decreased in group A compared with group B (hematocrit 46 (4)%; P < 0.0001; albumin 4.3 (0.3) g/dl; P = 0.0005) and group C (hematocrit 45 (3)%; P = 0.005; albumin 4.6 (0.3) g/dl; P < 0.0001). No difference was found in whole blood viscosity and levels of protein C. There also was no significant difference demonstrated between any of the parameters studied when comparing groups B and C. In conclusion, these results indicate that diabetic patients with a foot ulcer undergo an acute phase reaction as evidenced by a rise in C-reactive protein and fibrinogen compared with diabetic patients without a foot ulcer and normal control patients. As more is learned about the acute phase reaction, this information may prove valuable in the management of the diabetic patient.
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PMID:An acute phase reaction in diabetic patients with foot ulcers. 915 20

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.
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PMID:The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. 918 84

To clarify the abnormalities of coagulation and fibrinolytic systems on predialysis patients with chronic renal failure, we measured indices of coagulation and fibrinolytic systems in 33 predialysis patients whose creatinine (Cr) levels were over 3.0 mg/dl. We termed twenty-four patients with chronic glomerulonephritis the "CGN group". We also termed nine patients wit diabetes mellitus the "DM group". We measured thrombin.antithrombin III complex (TAT), alpha 2-plasmin inhibitor plasmin complex (PIC), D-dimer, protein C, protein S, thrombomodulin (TM), vitronectin, tissue plasminogen activator.plasminogen activator inhibitor-1 complex (tPAI-C) in theses two groups. Furthermore, we measured the same indices after 6 months in the CGN group. As a result, the plasma levels of both TAT, PIC, TM/Cr ration in the DM group were significantly higher that those in the CGN group, changes in both protein S activities and plasma levels of tPAI-C were reduced significantly after 6 months. In conclusion, the abnormalities of coagulation and fibrinolytic systems in predialysis diabetic patients were stronger than those in predialysis patients with CGN. Furthermore, these abnormalities were worsened after 6 months in predialysis patients with chronic renal failure.
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PMID:[Study on coagulation fibrinolytic systems in predialysis patients with chronic renal failure--comparison between patients with chronic glomerulonephritis and patients with diabetic nephropathy]. 928 13

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
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PMID:Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C. 943 45

A 19-yr-old woman with juvenile diabetes and protein C deficiency was referred for a bone scan to rule out osteomyelitis of the right tibia. The bone scan did not reveal evidence of osteomyelitis. There was, however, extraskeletal uptake of the 99mTc bone tracer in the anterior abdominal wall confined to the sites of subcutaneous heparin administration. This case is presented because of its interesting scintigraphic findings and to discuss the association of protein C deficiency and heparin administration as a cause of extraskeletal 99mTc bone tracer accumulation.
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PMID:Extraskeletal uptake of technetium-99m-MDP in sites of heparin administration. 959 96

Venous thromboembolism (VTE) is the third most common cardiovascular disease in the United States. VTE is usually a consequence of either acquired or inherited alterations in hemostatic regulatory proteins. These regulatory proteins are predominantly those of the protein C/protein S natural anticoagulant pathway. Acquired deficiencies in this pathway are frequently a consequence of other clinical entities (eg, cancer, AIDS, and diabetes), while inherited deficiencies can be responsible for venous thrombosis in an otherwise healthy individual. The purpose of this article is to briefly describe the pathobiology of the anticoagulant protein system and to review the clinical implications of activated protein C resistance.
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PMID:The role of activated protein C resistance in the pathogenesis of venous thrombosis. 970 65


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