PAI-1 concentrations in first-degree relatives of patients with non-insulin-dependent diabetes: metabolic and genetic associations.
OBJECTIVE
To identify whether levels of PAI-1 are elevated in relatives of NIDDM patients and the extent to which they relate to features of insulin resistance and to genotype at a common PAI-1 promoter polymorphism.


RESULTS
In 132 first-degree relatives of NIDDM patients and 151 controls PAI-1 activity was higher in relatives 14.4 U/ml than controls 9.3 U/ml (p < 0.0005) with higher body mass index 27.3 v. 24.7 kg/m2 p < 0.0005, fasting insulin 9.3 v. 7.6 mU/l p < 0.005 and triglyceride 1.4 v. 1.2 mmol/l p < 0.05. PAI-1 activity levels were higher in men and in smokers and showed a trend to being higher with increasing number of 4G alleles at the PAI-1 promoter polymorphism. After adjustment for age, sex, smoking, BMI and triglyceride levels, PAI-1 levels remained 26% higher in the NIDDM relatives (p = 0.01).


CONCLUSIONS
In relatives of NIDDM patients PAI-1 levels are elevated, presenting an additional mechanism for their increased cardiovascular risk.
Mansfield
M W
MW
Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, UK.
Stickland
M H
MH
Grant
P J
PJ
D000328:Adult; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004739:England / Q000453:epidemiology; D005190:Family; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1