Plasminogen activator inhibitor-1 is associated with coronary artery calcium in Type 1 diabetes

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, CO 80262, USA.
Journal of diabetes and its complications (Impact Factor: 3.01). 10/2008; 23(6):387-93. DOI: 10.1016/j.jdiacomp.2008.07.002
Source: PubMed


Elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of fibrinolysis, is associated with coronary artery disease (CAD). This association may not be independent of factors related to insulin resistance (IR). Patients with Type 1 diabetes mellitus have increased CAD and an increase in sub-clinical CAD which develops earlier in life. It is not known if PAI-1 is associated with sub-clinical CAD in Type 1 diabetes or if this association is independent of IR.
Type 1 diabetes patients (n=560) and participants without diabetes (n=693) were assessed for coronary artery calcium (CAC), a surrogate for subclinical CAD, by electron-beam computed tomography. PAI-1 was associated with CAC in both Type 1 diabetes (OR=1.32, 95% CI=1.12-1.58) and non-diabetes (OR=1.34, 95% CI=1.13-1.58), after controlling for traditional risk factors not associated with IR. In Type 1 diabetes, the relationship between PAI-1 and CAC was strongest for younger participants (P=.02 for PAI-1-by-age interaction) after controlling for factors related to IR. PAI-1 was positively associated with CAC for Type 1 diabetes participants younger than 45 years of age.
PAI-1 levels are independently related to CAC in younger Type 1 diabetes participants. PAI-1 levels were not independently related to CAC in non-diabetes participants.

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    • "We noted a positive correlation between the PAI-1 levels and the traditional risk factors of increased cardiovascular risk. In a recent study PAI-1 levels independently related to coronary artery calcium, a surrogate for subclinical CVD, in young people with Type 1 diabetes [34]. Plasma ICAM-1 levels have been shown to be associated with several established cardiovascular risk factors [14,35]. "
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    ABSTRACT: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of endothelial nitric oxide synthase (eNOS) that is associated with endothelial dysfunction, and is a risk marker for cardiovascular disease, a significant problem in Type 1 diabetes. The aim of the present study was to measure circulating ADMA, and define its association with endothelial dysfunction and endothelial markers in people with Type 1 diabetes with low likelihood of macrovascular disease. Sixty-one young people with Type 1 diabetes without macrovascular disease or nephropathy and 62 healthy volunteers underwent brachial artery flow-mediated dilatation (FMD) and assay of plasma ADMA and adhesion molecules. Age, gender, BMI, lipid profile and renal function were similar in the two groups. People with Type 1 diabetes had impaired FMD compared to healthy controls (5.0 +/- 0.4 vs 8.9 +/- 0.4%; p < 0.001). Plasma ADMA levels were significantly lower in the people with diabetes compared to healthy controls (0.52 +/- 0.12 vs 0.66 +/- 0.20 micromol/l, p < 0.001). Plasma ICAM-1, E-selectin and PAI-1 levels were significantly higher in people with diabetes compared to healthy controls (median 201 (IQR 172-226) vs 180 (156-216) microg/l, p = 0.027; 44.2 (32.6-60.9) vs. 33.1 (22.4-51.0) microg/l; p = 0.003 and 70.8 (33.3-85.5) vs 46.3 (23.9-76.8) microg/l, p = 0.035). Plasma ADMA and VCAM-1 levels were positively correlated (r = 0.37, p = 0.003) in people with diabetes. There was no correlation between the plasma ADMA and FMD. ADMA levels are not associated with endothelial dysfunction in young adults with Type 1 diabetes without microalbuminuria or known macrovascular disease. This suggests that the impaired endothelial function in these individuals is not a result of eNOS inhibition by ADMA.
    Cardiovascular Diabetology 06/2009; 8(1):27. DOI:10.1186/1475-2840-8-27 · 4.02 Impact Factor
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    ABSTRACT: Objectives: Type 1 diabetes is a chronic disease that causes persistent vascular injury. This study investigates the benefits of surrogate markers in early detection of vascular injury in children and adolescents with type 1 diabetes. Methods: Eighty-four patients (35 male, 49 female) with type 1 diabetes for 5 or more years were included. Serum lipid profile, plasminogen activator inhibitor-1 (PAI-1), lipoprotein (a) (Lpa) and homocystein, were investigated. Patients were divided into two groups according to the duration of diabetes. Patients with and without microvascular complications were also compared. Results: Microvascular complications were present in 14 out of 48 patients in group-1 (29.1%; duration of diabetes: 5-10 years) and in 7 out of 36 patients in group-2 (19.4%; duration of diabetes: >10 years). Serum homocystein, Lpa, PAI-1 and serum lipids were not correlated with the duration of diabetes. Significantly increased triglyceride (TG) and HbA1C levels were associated with the presence of microvascular complications. Conclusion: Providing good glycemic control is very important for preventing vascular injury in children and adolescents with type 1 diabetes. It seems that traditional vascular surrogate markers like LDL/HDL ratio, triglycerides and HbA1C level correspond more to microvascular complications than newly defined surrogate markers that are not commonly available.
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    ABSTRACT: The presence of cardiovascular disease (CVD) in Type 1 diabetes largely impairs life expectancy. Hyperglycemia leading to an increase in oxidative stress is considered to be the key pathophysiological factor of both micro- and macrovascular complications. In Type 1 diabetes, the presence of coronary calcifications is also related to coronary artery disease. Cardiac autonomic neuropathy, which significantly impairs myocardial function and blood flow, also enhances cardiac abnormalities. Also hypoglycemic episodes are considered to adversely influence cardiac performance. Intensive insulin therapy has been demonstrated to reduce the occurrence and progression of both micro- and macrovascular complications. This has been evidenced by the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) study. The concept of a metabolic memory emerged based on the results of the study, which established that intensified insulin therapy is the standard of treatment of Type 1 diabetes. Future therapies may also include glucagon-like peptide (GLP)-based treatment therapies. Pilot studies with GLP-1-analogues have been shown to reduce insulin requirements.
    Cardiovascular Diabetology 10/2013; 12(1):156. DOI:10.1186/1475-2840-12-156 · 4.02 Impact Factor
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