Fibrinolytic capacity following stimulation with desmopressin acetate in patients with diabetes mellitus

Grant, Maria B.; Fitzgerald, Constance R.; Guay, C; Lottenberg, Richard

doi:10.1016/0026-0495(89)90239-4

Cited by 21 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings were surprising to us, and it would be very interesting to repeat our study in patients with type 2 diabetes, especially viewed against the abovementioned findings by Grant and colleagues (24). The main difference in the fibrinolytic function between patients with type 1 and type 2 diabetes is higher PAI-1 activity in type 2 diabetes (25,26), while the incorporation of antiplasmin in fibrin seems to be increased in both these patient groups (24) compared with control subjects.…”

Section: Discussionmentioning

confidence: 54%

Increased Incorporation of Antiplasmin Into the Fibrin Network in Patients With Type 1 Diabetes

et al. 2014

View full text Add to dashboard Cite

OBJECTIVEDiabetes is associated with various vascular complications and is suggested to induce a prothrombotic state. In the current study, we characterized antiplasmin incorporation into fibrin in relation to other fibrinolytic compounds in patients with type 1 diabetes. RESEARCH DESIGN AND METHODSA total of 236 patients with type 1 diabetes and 78 control subjects were investigated. The incorporation of antiplasmin into the fibrin network and the plasma levels of plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator (tPA) activity, tPA/PAI-1 complex, plasmin-antiplasmin complex, antiplasmin, factor XIII, and D-dimer were measured. In addition, we used global assays to study fibrinolysis. RESULTSThe incorporation of antiplasmin into the fibrin network was significantly higher in patients with type 1 diabetes than in control subjects without diabetes (1.65 6 0.25 vs. 1.35 6 0.18 mg/L, respectively; P < 0.0001). The patients also had lower PAI-1 activity (2.19 units/mL [interquartile range 0.96-5.42] vs. 4.25 units/mL [1.95-9.0]; P = 0.0012) and antiplasmin level in plasma (78.5 6 13.3 vs. 83.2 6 15.4 mg/L; P < 0.05), resulting in a higher fibrinolytic capacity (shorter clot lysis time; P = 0.0090). We did not find any important sex differences regarding fibrinolysis in the patients or in the control subjects. CONCLUSIONSPatients with type 1 diabetes incorporate more antiplasmin into the fibrin network than control subjects without diabetes do and have a reduced PAI-1 activity and a shorter clot lysis time. These results suggest that patients with type 1 diabetes produce a fibrin clot that is more resistant to fibrinolysis, which, however, may be counteracted by an increased fibrinolytic potential in plasma.Diabetes is linked to microvascular disturbances causing neuropathy, retinopathy, and nephropathy, as well as macrovascular complications such as stroke, coronary heart disease, and nonhealing foot ulcers (1). Hypercoagulability and impaired fibrinolysis are pathophysiologically important processes of vascular complications (2). Diabetes has been considered a prothrombotic state (3), partly due to impaired fibrinolysis (4), but has also been associated with increased risk of bleeding when

show abstract

Section: Discussionmentioning

confidence: 54%

Increased Incorporation of Antiplasmin Into the Fibrin Network in Patients With Type 1 Diabetes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Positive correlation between plasma PAI-1 and serum triglyceride levels have been demonstrated in several earlier studies [6,[12][13][14][36][37][38][39][40]. However, there are also a number of publications reporting on absence of this relationship [17,[41][42][43][44]. In our study, comprising randomly selected men, with and without hypertriglyceridaemia, we found significant and independent correlations between plasma PAI-1 activity and serum triglyceride concentration in the NTG group as well as in the entire HTG group.…”

Section: Discussionmentioning

confidence: 96%

Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men

et al. 1993

View full text Add to dashboard Cite

Impaired fibrinolytic function secondary to elevated plasma plasminogen activator inhibitor-1 activity, hypertriglyceridaemia and hyperinsulinaemia are frequent findings in patients with coronary heart disease. It has been debated whether VLDL or insulin is the major regulator of plasma plasminogen activator inhibitor-1 activity. This study examines the relationships between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, fasting and post-oral glucose load insulin levels and insulin sensitivity, as estimated by the minimal model method. Subjects studied were randomly selected hypertriglyceridaemic (n = 65) and age-matched normotriglyceridaemic (n = 61) men, aged 40-50 years, recruited in a population survey. Plasma plasminogen activator inhibitor-1 activity was higher in the hypertriglyceridaemic than in the normotriglyceridaemic group (21 +/- 14 vs 10 +/- 8 mU/l; p < 0.01). The hypertriglyceridaemic group had higher serum insulin, basal as well as 2 h after intake of the oral glucose load, and a lower insulin sensitivity index. In univariate analysis, plasma plasminogen activator inhibitor-1 activity correlated positively with VLDL triglycerides in both the hyper- and normotriglyceridaemic groups (r = 0.43 r = 0.60, respectively) and negatively with the insulin sensitivity index (r = -0.35 r = -0.44, respectively). In multivariate analysis, VLDL triglyceride levels were found to be independently related to plasma plasminogen activator inhibitor-1 activity in both groups, whereas insulin sensitivity/serum insulin levels were not. An unexpected finding was that the serum activity of the enzyme gamma glutamyl transpeptidase appeared to influence the relationships for plasma plasminogen activator inhibitor-1 in the hypertriglyceridaemic group.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…Whereas Juhan-Vague et al (8) have studied very obese non-insulin dependent diabetic patients in comparison with nonobese control subjects (mean body mass index 30.1 vs 23.2), in the present study the body mass index of patients and control subjects was very similar (median 26.0 vs 25.9). Grant et al (14) have studied PAI-1 levels in both type 1 and 2 diabetic patients and concluded from their results that the elevation of PAI-1 appears related to obesity and not to diabetes per se. This is also in line with the classical results of Aimer and Nilsson presented in 1974.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Insulin Treatment on the Balance between Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Type 2 Diabetic Patients

et al. 1992

View full text Add to dashboard Cite

SummaryBeside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40). In conclusion, our results indicate that insulin treatment associated with metabolic improvement has no adverse effect to fibrinolysis in type 2 diabetic patients.

show abstract

Fibrinolytic capacity following stimulation with desmopressin acetate in patients with diabetes mellitus

Cited by 21 publications

References 28 publications

Increased Incorporation of Antiplasmin Into the Fibrin Network in Patients With Type 1 Diabetes

Increased Incorporation of Antiplasmin Into the Fibrin Network in Patients With Type 1 Diabetes

Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men

The Effect of Insulin Treatment on the Balance between Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Type 2 Diabetic Patients

Contact Info

Product

Resources

About