Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes.
BACKGROUND
Several studies have shown that fibrinolytic and coagulation abnormalities as well as low-grade inflammation predict cardiovascular disease and type 2 diabetes. We studied in the Insulin Resistance Atherosclerosis Study the relation of incident diabetes to dynamic changes of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen.


RESULTS
After a follow-up of 5.2 years, diabetes developed in 140 (16.6%) of 843 individuals (57% women; mean age [range], 54.7 [40, 69] years) (converters versus nonconverters). Baseline and follow-up levels of PAI-1 and fibrinogen (demographically and smoking adjusted) were higher in converters versus nonconverters (mean [SE]): at baseline, 23.7 ng/mL (1.5) versus 14.5 (0.4) and 286.2 mg/dL (4.8) versus 273.6 (2.1); at follow-up, 45.3 ng/mL (3.2) versus 25.9 (0.8) and 292.0 mg/dL (5.6) versus 275.2 (2.5); all P<0.05. In a demographically and smoking-adjusted logistic regression model, the change in PAI-1 was related to incident diabetes (OR for a 1-SD change [CI], 1.75 [1.37, 2.22]; P<0.001) after adjusting for baseline PAI-1 levels. After further adjusting for insulin sensitivity (SI) or waist, change in PAI-1 remained significantly related to incident diabetes (OR, 1.66 [1.28, 2.15], and 1.64 [1.28, 2.10]; P<0.001). In contrast, change in fibrinogen was not significantly related to incident diabetes.


CONCLUSIONS
Progression of PAI-1 levels over time, in addition to high baseline PAI-1 levels, is associated with incident diabetes. PAI-1 levels (but not fibrinogen) further increase with the rising glucose levels and the development of diabetes. These findings extend the current knowledge on the relation of fibrinolysis and coagulation abnormalities to the development of type 2 diabetes.
Festa
Andreas
A
Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
Williams
Ken
K
Tracy
Russell P
RP
Wagenknecht
Lynne E
LE
Haffner
Steven M
SM
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*
D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen