PAI-1 Concentrations in First-degree Relatives of Patients with Non-insulin-dependent Diabetes: Metabolic and Genetic Associations

AIM: 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). CONCLUSION: In relatives of NIDDM patients PAI-1 levels are elevated, presenting an additional mechanism for their increased cardiovascular risk.