PLASMINOGEN-ACTIVATOR INHIBITOR (PAI-1) ACTIVITY IS ELEVATED IN ASIANAND CAUCASIAN SUBJECTS WITH NON-INSULIN-DEPENDENT (TYPE-2) DIABETES BUT NOT IN THOSE WITH IMPAIRED GLUCOSE-TOLERANCE (IGT) OR NONDIABETIC ASIANS

In order to study the plasminogen activator inhibitor activity (PAI-1) in subjects at different risk of non-insulin-dependent diabetes and i schaemic heart disease we examined 89 subjects with diet controlled NI DDM (49 Caucasian, 40 Asian), 29 with impaired glucose tolerance (IGT) (13 Caucasian, 16 Asian), and 149 with normal glucose tolerance (67 C aucasian, 82 Asian). Diabetes was diagnosed by WHO criteria and highly specific, monoclonal antibody-based assays were used to measure insul in, intact proinsulin, and des 31,32 proinsulin. Subjects with NIDDM w ere significantly more obese, had more central distribution of obesity , higher fasting plasma specific insulin concentrations (NIDDM median 74 pmol l(-1) vs IGT 41 pmol l(-1), p < 0.01 and vs normals 34 pmol l( -1), p < 0.001) and higher PAI-1 activity than normals and those with IGT (NIDDM 23.0 +/- 6.9 vs IGT 16.8 +/- 5.0, p < 0.001 and vs normals 17.1 +/- 6.9 AU ml(-1), p < 0.001). However, PAI-1 activity was not si gnificantly different between Asian and Caucasian normals (17.5 +/- 7. 3 vs 16.5 +/- 6.4 AU ml(-1), p = ns) and diabetic (22.8 +/- 7.3 vs 23. 1 +/- 6.6 AU ml(-1), p = ns) subjects. In addition to relationships wi th obesity and plasma triglyceride, PAI-1 activity, after controlling for age, sex, body mass index, and waist-hip ratio, was related to fas ting insulin (partial r = 0.22, p < 0.001), intact proinsulin (partial r = 0.36, p < 0.001), and des 31,32 proinsulin concentrations (partia l r = 0.33, p < 0.001) as measured by highly specific assays. The asso ciation of PAI-1 with diabetes was weakened but remained statistically significant (p = 0.042) after controlling for age, sex, ethnicity, ob esity, plasma triglyceride, and all insulin-like molecules. We conclud e that, although PAI-1 activity is raised in subjects with diet-treate d NIDDM, it is normal in subjects with IGT and nondiabetic Asians, pop ulations at high risk of NIDDM and ischaemic heart disease. Raised PAI -1 activity may play an important role in the pathogenesis of macrovas cular disease in subjects with NIDDM, but is unlikely to explain exces s risk of ischaemic heart disease in Asians and those with impaired gl ucose tolerance.