Evidence for a Reduced Heparin Cofactor II Biological Activity in Diabetes

Ceriello, Antonio; Quatraro, A; P, Dello Russo; Marchi, E.; Mr, Milani; Giugliano, Dario

doi:10.1159/000216150

Cited by 5 publications

(8 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most studies indicate that in diabetic patients, hyperglycemia may affect the activities of different CI possibly by nonenzymatic glycosylation [4,32,33,39,40]. However, in our study, we found comparable plasma antigenic levels and functional activities of all coagulation inhibitors (ATIII, HCII, PC, PS) in poorly controlled diabetic patients and healthy subjects.…”

Section: Discussioncontrasting

confidence: 78%

“…Divergent results (elevated, decreased, normal plasma levels) had been found for ATIII, HCII, PC and PS. However, most investigators reported normal antigenic plasma levels in the face of decreased functional activities of ATIII [30,31], HCII [32][33][34], PC and PS [21, 23-25, [35][36][37] which may represent a functional abnormality due to nonenzymatic glycosylation of these proteins. However, there is no paper in the literature that studied all CI and/or investigated the effect of poor (PGC) and good glycemic control (GGC) on plasma levels and activities of CI in the same diabetic patient group.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glycemic Control and Coagulation Inhibitors in Diabetic Patients

Altunbaş

Karayalçın

Ündar

1998

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

Objective: To investigate the plasma antigenic levels and functional activities of coagulation inhibitors in poorly controlled diabetic patients and the possible effect of good glycemic control on these parameters. Research Design and Methods: Both functional activities and plasma antigenic levels of coagulation inhibitors (antithrombin III, heparin cofactor II, protein C, and protein S) and plasma levels of C4b-binding protein were measured in 28 diabetic patients (13 males, 15 females; 2 IDDM, 26 NIDDM; median age 56.5 years; median duration of diabetes 5.5 years) with poor glycemic control (median HbA_1c 11.8%). Twenty-three healthy subjects were enrolled as controls. Following a 3-month intensification of antihyperglycemic therapy, good glycemic control (HbA_1c <8%) was achieved in 17 patients, and the plasma levels of the same parameters during this period were compared with baseline values. Results: Functional activities and plasma antigenic levels of coagulation inhibitors were comparable in poorly controlled diabetic patients and healthy subjects. In patients achieving good control after 3 months, there was a significant reduction in plasma antigenic levels of protein S (p = 0.005) and C4b-binding protein (p = 0.03); however, no difference could be observed in other parameters. HbA_1c did not show any correlation with plasma antigenic levels or functional activities of coagulation inhibitors either at baseline or at 3 months of good glycemic control. Conclusions: Our findings suggest that in poorly controlled diabetic patients, coagulation inhibitors are not different from healthy controls. Short-term good glycemic control may not exert a profound effect on coagulation inhibitors except protein S and its binding protein, C4b-binding protein.

show abstract

Section: Discussioncontrasting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Glycemic Control and Coagulation Inhibitors in Diabetic Patients

Altunbaş

Karayalçın

Ündar

1998

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

show abstract

“…In fact, its decreased biological activity results in a reduced thrombin-antithrombin complex formation with consequent hyperactivity of the thrombin [25]. Similar to ATIII, a reduction in biological activity, directly affected by metabolic control, has also been reported for heparin co-factor II, another plasma protease which inhibits thrombin [26].…”

Section: Coagulation Inhibitorsmentioning

confidence: 91%

Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects

1993

View full text Add to dashboard Cite

Numerous studies have shown that coagulation abnormalities occur in the course of diabetes mellitus, resulting in a state of thrombophilia. These observations are supported by epidemiological studies which demonstrate that thromboembolic events are more likely to occur in diabetic patients. The coagulation abnormalities observed in diabetic patients seem to be caused by the hyperglycaemia, which also constitutes the distinguishing feature of this disease. These data are also supported by in vitro studies which demonstrate how glucose can directly determine alterations in the coagulation system. The abnormalities observed involve all stages of coagulation, affecting both thrombus formation and its inhibition, fibrinolysis, platelet and endothelial function. The final result is an imbalance between thrombus formation and dissolution, favouring the former. Hyperglycaemia probably determines the onset of these abnormalities through three mechanisms which are, respectively, non-enzymatic glycation, the development of increased oxidative stress and a decrease in the levels of heparan sulphate. The first seems to affect the functionality of key molecules of coagulation in a negative sense. Oxidative stress constitutes an important pro-thrombotic stimulus, while the decrease in heparan sulphate determines a reduction in antithrombotic defenses. Good metabolic control could play a key role in controlling the coagulation irregularities in diabetes. However, considering the difficulties in achieving such an objective, it is possible that the use of drugs may represent a valid alternative. In fact, several drugs exist which are of potential interest. It is, however, necessary to perform long-term studies which demonstrate unequivocably that by controlling the coagulation abnormalities in diabetic patients, prolongation of life is possible.

show abstract

“…9 a-Tocoperol is a potent anti-oxidant and is an anti-glycating substance in vitro. 10 More recently the combination of vitamins C and E more efficiently inhibited glycation and AGE than the single vitamins, and this is an evidence for the inhibition of glycation by anti-oxidants. 11…”

Section: Introductionmentioning

confidence: 99%