title: Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (PAI-1) activity and proinsulin-like molecules independently of glycaemic control.
abstract: Eleven Type 2 diabetic subjects (10 male 1 female: age 56.2 +/- 9.7 (SD) yr) were treated in random order either with insulin or with sulphonylureas for 8 weeks each, without attempting to alter glycaemic control between the two treatment periods. Insulin treatment was associated with suppression of endogenous insulin secretion (fasting C-peptide levels -35.0 +/- 24.2%; p = 0.006), and of intact proinsulin (-43.1 +/- 36.8%; p = 0.03) and 32,33 split proinsulin -20.1 +/- 27.0%; p = 0.03). Activity of plasminogen activator inhibitor (PAI-1), a fast acting inhibitor of fibrinolysis, decreased significantly (-14.3% +/- 27.5%; p = 0.02) but no changes occurred in concentration of lipoproteins or apoproteins between therapies. Changes in concentrations of 32,33 split and intact proinsulin were closely and significantly related (rs = 0.83; p < 0.001) to each other but not with changes in concentrations of C-peptide (intact proinsulin rs = -0.41; p = 0.11) and 32,33 split proinsulin rs = -0.27; (p = 0.21). Percentage changes in intact proinsulin concentrations were positively correlated with those in PAI-1 (rs = 0.51; p = 0.05). There was, however a paradoxical negative relationship between changes in C-peptide concentrations and those of PAI-1 (rs = -0.73; p = 0.006). These preliminary observations suggest that insulin treatment in Type 2 diabetic subjects without any changes in glycaemic control is associated with a reduced activity of PAI-1, but is without effect on any other cardiovascular risk factors. Concentrations of insulin precursor molecules may play a role in determining fibrinolytic activity.
authors.affiliation: Department of Medicine, University College and Middlesex School of Medicine, Whittington Hospital, London, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Jain
authors.forename: D K
authors.initials: DK
authors.lastname: Nagi
authors.forename: B M
authors.initials: BM
authors.lastname: Slavin
authors.forename: P J
authors.initials: PJ
authors.lastname: Lumb
authors.forename: J S
authors.initials: JS
authors.lastname: Yudkin
mesh_terms: D001053:Apolipoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011384:Proinsulin / Q000097:blood*; D012044:Regression Analysis
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D011384:Proinsulin