Proinsulin-like molecules and plasminogen activator inhibitor type 1 (PAI-1) activity in diabetic and non-diabetic subjects with and without myocardial infarction

• Published in: Atherosclerosis Vol. 130; no. 1; pp. 171 - 178
• Main Authors: Gray, Rosaire P, Panahloo, Arshia, Mohamed-Ali, Vidya, Patterson, David L.H, Yudkin, John S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.04.1997; Elsevier
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Heart; Humans; Insulin - blood; Insulin sensitivity; Male; Medical sciences; Middle Aged; Myocardial infarction; Myocardial Infarction - complications; NIDDM; PAI-1; Plasma insulin; Plasminogen Activator Inhibitor 1 - blood; Proinsulin - blood; Proinsulin-like molecules; Protein Precursors - blood; Serum triglycerides; Triglycerides - blood; Myocardial infarction; Serum triglycerides; Plasma insulin; Insulin sensitivity; PAI-1; Proinsulin-like molecules; NIDDM; Endocrinopathy; Human; Proinsulin; Infarct; Cardiovascular disease; Exploration; Triglyceride; Coronary heart disease; Myocardial disease; Non insulin dependent diabetes; Insulin; Plasminogen activator inhibitor 1; Sensitivity; Association; Myocardium; Serum
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(96)06070-4

Elevated plasminogen activator inhibitor type 1 (PAI-1) activity has been shown to correlate with plasma insulin, proinsulin-like molecules, serum triglycerides and insulin sensitivity in both non-insulin dependent diabetic (NIDDM) subjects and subjects with coronary heart disease. We examined the relative roles of these variables in determining PAI-1 activity in four groups of male caucasian subjects: non-diabetic subjects with ( n=38) and without ( n=38) previous myocardial infarction (MI) and NIDDM subjects with ( n=26) and without ( n=30) previous MI. Insulin and proinsulin-like molecules were measured using specific two-site immunometric assays and insulin sensitivity estimated using the Homeostasis Model Assessment (HOMA) model. Subjects were comparable in age and body mass index. In univariate analysis, there were significant correlations of PAI-1 activity with intact and des-31,32-proinsulin and serum triglycerides in non-diabetic subjects with ( r=0.52, P=0.001; r=0.58, P<0.001; r=0.41, P=0.010) and without ( r=0.31, P=0.056; r=0.46, P=0.006; r=0.41, P=0.011) MI, but not with plasma insulin or insulin sensitivity. In NIDDM subjects, PAI-1 activity correlated significantly with intact and des-31,32-proinsulin and serum triglyceride ( r=0.47, P=0.015; r=0.58, P=0.002; r=0.44, P=0.026) only in subjects with MI. In multiple regression analysis, MI was the most important determinant of PAI-1 activity levels ( r 2=0.31, F=55.6, P<0.001). In conclusion, concentrations of proinsulin-like molecules and serum triglycerides appear to be stronger determinants of PAI-1 activity than plasma insulin or insulin sensitivity in both NIDDM subjects and non-diabetic subjects with and without MI. However, the relationship of MI with PAI-1 activity is independent of these variables.