Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: effects of insulin and glucose.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation.


OBJECTIVE
Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM.


METHODS
Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia.


METHODS
The study took place at a clinical research center.


METHODS
Participants included 18 T2DM patients and 22 nondiabetic controls.


RESULTS
Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2-4 h resulted in a small ( approximately 7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA.


CONCLUSIONS
We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.
Boden
Guenther
G
Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. bodengh@tuhs.temple.edu
Vaidyula
Vijender R
VR
Homko
Carol
C
Cheung
Peter
P
Rao
A Koneti
AK
D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005167:Factor VII / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis* / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*