Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia increases plasminogen activator inhibitor 1 in blood in normal human subjects.
Hypofibrinolysis caused by increased plasminogen activator inhibitor 1 (PAI-1) has been implicated in the vasculopathy of type 2 diabetes, typified by increased insulin, glucose, and triglycerides. However, short-term infusions of insulin have not increased PAI-1 in normal subjects. We hypothesized that induction of increased insulin accompanied by increased glucose and triglycerides would increase PAI-1. Accordingly, 30% glucose and 10% Intralipid were infused for 6 h in ten normal lean individuals (54 +/- 3 years) resulting in increased insulin (42 +/- 5 microU/dl), glucose (200 +/- 24 mg/dl), and triglycerides (425 +/- 45 mg/dl), simulating changes in type 2 diabetes. In contrast to results with infusion of saline alone (n = 16) and euglycemic-hyperinsulinemic clamps (n = 10, serum insulin = 89 +/- 7 microU/dl), PAI-1 in blood increased significantly 6 h after the onset of infusion (15 +/- 5 ng/ml, P < 0.05 vs. baseline = 7.4 +/- 1.1, saline 6 h = 3.4 +/- 1.1, and insulin alone 6 h = 3.7 +/- 0.8) and remained elevated for an additional 6 h (combined infusion = 13.8 +/- 3.8 ng/ml, saline = 6.7 +/- 2 ng/ml, insulin alone = 7.8 +/- 1.7 ng/ml, P = 0.06). Our data suggest that combined hyperinsulinemia, hypertriglyceridemia, and hyperglycemia are likely to contribute to hypofibrinolysis of type 2 diabetes by increasing the blood levels of PAI-1. Moreover, these results underscore the potential importance of modifying insulin resistance as well as achieving glycemic and lipidemic control in individuals with type 2 diabetes.
Calles-Escandon
J
J
Department of Medicine, The University of Vermont College of Medicine, Burlington 05405, USA. jcallese@zoo.uvm.edu
Mirza
S A
SA
Sobel
B E
BE
Schneider
D J
DJ
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005260:Female; D005342:Fibrinolysis; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications*; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications*; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*
D005217:Fat Emulsions, Intravenous; D017395:Plasminogen Activator Inhibitor 1; D005947:Glucose