Blood Fibrinolytic Activity in Diabetes Mellitus and Its Bearing on Ischaemic Heart Disease and Obesity

Fearnley, G. R.; Chakrabarti, Ranjan; Avis, P. R. D.

doi:10.1136/bmj.1.5335.921

Cited by 133 publications

(43 citation statements)

References 10 publications

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“…A reduced degradation of fibrin clots in vivo may contribute to the deposition and accumulation of fibrin and several other proteins observed in those tis sues most frequently affected by the compli cations of diabetes [9], The literature about the state of the fibrinolytic system in dia betes mellitus is confusing. Some studies showed abnormally low [14][15][16][17][18][19][20] and other studies abnormally high fibrinolytic activity in diabetics [21][22][23]. The results of this study might suggest an explanation for the discrep ancies reported, because we could demon strate a glycometabolic control dependency of the D-dimers-measurable, overall fibrino lysis effect in diabetics.…”

Section: Discussioncontrasting

confidence: 40%

Glycometabolic Control and Fibrinolysis in Diabetic Patients

Wersch

Westerhuis²,

Venekamp³

1990

Pathophysiol Haemos Thromb

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We investigated 148 diabetic patients with regard to their relationship between fibrinolysis (D-dimer and plasminogen activator inhibitor; PAI) and glycometabolic control (HbA_1c, HbA₁ and fructosamine). The percentage of moderately controlled patients as indicated by HbA_1c, HbA₁ and fructosamine is relatively high (29.7, 41.7 and 30.4%, respectively). Simultaneously, the D-dimer and PAI levels turned out to be enhanced in 30.8 and 22.4% of the patients. There was a positive nonsignificant correlation between D-dimer and HbA_1c, a highly significant negative correlation between D-dimer and HbA₁ and a nonsignificant negative correlation between D-dimer and fructosamine. According to the upper limits of the distinct reference ranges for HbA_1c, HbA₁ and fructosamine, we splitted up the .D-dimer results and calculated the mean D-dimer values belonging to each category. Comparing the D-dimer means for each parameter, we separately obtained significant differences of the D-dimer means between the lower and higher HbA₁ and fructosamine groups, whereas in the case of HbA_1c the mean D-dimer values of the categories under and over 9% showed no significant difference. For PAI, we found only weak nonsignificant positive correlations to D-dimer and fructosamine and weak but highly significant correlations to HbA_1c. These results are indicative for an increase of PAI with diminished glycometabolic control as measured with the HbA_1c and fructosamine level. Both D-dimer and PAI showed positive, highly significant correlations to the age of the diabetic patients, whereas HbA_1c and fructosamine were age independent. The results described in this report demonstrate that the fibrin degradation to D-dimer fragments by the specific fibrinolytic enzyme plasmin is dependent on the glycometabolic control state as measured with HbA₁ and fructosamine and thus on the nonenzymatic glycosylation, which reduces the susceptibility of fibrin to degradation by plasmin.

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Section: Discussioncontrasting

confidence: 40%

Glycometabolic Control and Fibrinolysis in Diabetic Patients

Wersch

Westerhuis²,

Venekamp³

1990

Pathophysiol Haemos Thromb

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“…Although decreased fibrinolytic activity has been described in diabetic patients (10,24,25) and hypoglycemic agents (6,8,9,26,27) have been shown to increase plasma fibrinolytic activity, the mechanism underlying the fibrinolytic effect of these agents has not been elucidated. The results of the present investigation using BAE cells have demonstrated that sulfonylureas stimulate the synthesis and secretion of PAs, and thus suggest that that is the mechanism of action for the in vivo fibrinolytic effect of the sulfonylureas.…”

Section: Discussionmentioning

confidence: 99%

“…gen (Kabi grade L), 0.2 U/ml thrombin (Sigma Chemical Co.), 1% low molecular weight agarose (Bio-Rad Laboratories), 25 gg/ml purified human plasminogen, and 0.5 U/ml UK. All these materials were prepared in PBS, pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

Effects of sulfonylureas on the synthesis and secretion of plasminogen activator from bovine aortic endothelial cells.

Kuo¹,

Korner²,

Bjornsson³

1988

J. Clin. Invest.

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The effects of sulfonylureas on the production of plasminogen activator (PA) and antiactivator (PAI) were investigated using bovine aortic endothelial cells. All compounds studied stimulated PA release (1.3-to 5.2-fold), with glipizide being the most potent, followed by tolazamide, chlorpropamide, and tolbutamide, in that order, while glyburide was the least effective. Both tissue-type and urokinase-type PA production was enhanced. Studies using metabolic inhibitors indicated that both RNA and protein syntheses are required for the sulfonylureamediated stimulation of PA release. In addition to continuous release of the two PAs, there was also a continuous release of a single PAI, which did not show an increase after the sulfonylureas. These results suggest that, in addition to their beneficial effects in the treatment of diabetes mellitus, some sulfonylurea compounds may also have significant thrombolytic effects. These results also suggest that pharmacological enhancement of PA production by vascular endothelial cells may be a promising antithrombotic mechanism.

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“…1 Elevated levels of these proteins were also associated with infarction risk factors, such as obesity, diabetes mellitus, and angina pectoris. 2 Despite these intriguing associations, the increase in systemic inflammation was generally thought to be a result of local atheromatous inflammation. The pathogenic significance of systemic inflammation was mostly eclipsed by the vigorous advances in lipid research.…”

mentioning

confidence: 99%

Adipose Tissue, Inflammation, and Cardiovascular Disease

Berg

Scherer

2005

Circulation Research

1,812

1,331

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Abstract-Mounting evidence highlights the role of adipose tissue in the development of a systemic inflammatory state that contributes to obesity-associated vasculopathy and cardiovascular risk. Circulating mediators of inflammation participate in the mechanisms of vascular insult and atheromatous change, and many of these inflammatory proteins are secreted directly from adipocytes and adipose tissue-derived macrophages. Several factors linking obesity with an increased cardiovascular risk have been identified. The adipocyte-specific secretory protein adiponectin is a particularly promising candidate in this context. Its levels are decreased in obesity. Adiponectin may mediate some of its demonstrated cardioprotective effects through its anti-inflammatory properties. In addition to decreased expression of beneficial adipokines, secretion of a host of inflammatory factors from visceral adipose tissue may contribute to the increased cardiovascular risk associated with obesity. The cardioprotective effects of many of the most popular drug regimens corroborate these conclusions, demonstrating that along with improvements in other therapeutic end points, they mediate improvements in systemic inflammation. In some cases, these improvements are attributable to direct suppression of inflammatory signaling in adipocytes.

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Blood Fibrinolytic Activity in Diabetes Mellitus and Its Bearing on Ischaemic Heart Disease and Obesity

Cited by 133 publications

References 10 publications

Glycometabolic Control and Fibrinolysis in Diabetic Patients

Glycometabolic Control and Fibrinolysis in Diabetic Patients

Effects of sulfonylureas on the synthesis and secretion of plasminogen activator from bovine aortic endothelial cells.

Adipose Tissue, Inflammation, and Cardiovascular Disease

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