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DETERMINANTS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY IN TREATED NIDDM AND ITS RELATION TO A POLYMORPHISM IN THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 GENE

PANAHLOO, A; MOHAMEDALI, V; LANE, A; GREEN, F; HUMPHRIES, SE; YUDKIN, JS; (1995) DETERMINANTS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY IN TREATED NIDDM AND ITS RELATION TO A POLYMORPHISM IN THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 GENE. DIABETES , 44 (1) 37 - 42.

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Abstract

Plasminogen activator inhibitor 1 (PAI-1) activity is increased in patients with non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to their excess risk of cardiovascular disease. We examined the determinants of PAT-I activity in 146 NIDDM subjects by using specific assays of insulin and intact and des-31,32-proinsulin and measures of insulin resistance, relating these measurements to serum Lipids, hypoglycemic therapy, and a common 4G/5G polymorphism in the promoter region of the PAI-I gene. Subjects were treated with insulin, sulfonylurea, sulfonylurea plus metformin, metformin, and diet alone. In the whole group, PAT-I activity correlated significantly with serum triglycerides (r = 0.39, P < 0.001), specific insulin (r = 0.29, P < 0.001), intact proinsulin (r = 0.24, P = 0.004), and des-31,32-proinsulin (r = 0.30, P < 0.001) and in subjects not on insulin (n = 110), with insulin sensitivity (r = -0.42, P < 0.001). There was a significant difference in PAI-1 activity among the three genotypic groups (P = 0.016); subjects with the genotype 4G/4G had PAI-1 levels one-third higher than those with the 5G/5G genotype. In the 4G/4G group, PAI-1 activity correlated significantly with triglyceride levels (r = 0.65, P < 0.0001). There was no significant difference in PAI-1 activity in the different treatment groups despite a significant difference in concentrations of intact and des-31,32-proinsulin. In a multiple regression model, insulin sensitivity and the interaction between PAI-1 4G/5G genotype and triglyceride were the strongest determinants of PAI-1 activity. In conclusion, in this sample of NIDDM subjects, the influence of triglyceride on PAI-1 seems to be genotype dependent, and this interaction is a major determinant of PAI-1 activity.

Type:Article
Title:DETERMINANTS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY IN TREATED NIDDM AND ITS RELATION TO A POLYMORPHISM IN THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 GENE
Keywords:LINE HEP G2, PLASMA-INSULIN, ENDOTHELIAL-CELLS, RISK-FACTORS, CARDIOVASCULAR-DISEASE, DIABETIC-PATIENTS, OBESE SUBJECTS, PAI-1, RESISTANCE, METFORMIN
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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