Plasminogen Activator Inhibitor-1 Predicts Negative Alterations in Whole-Body Insulin Sensitivity in Chronic HIV Infection.
Plasminogen activator inhibitor type 1 (PAI-1), a key negative regulator of fibrinolysis, has been investigated to be one of the potential mechanisms of the development of impaired insulin sensitivity, insulin resistance, and diabetes mellitus. Because chronically stable HIV-infected individuals frequently develop abnormal glucose metabolism, including insulin resistance and diabetes mellitus, we postulated that PAI-1 could be one of the multifactorial pathogenic roles in the development of impaired insulin sensitivity and insulin resistance among chronic HIV-infected individuals. From our longitudinal cohort study, we selectively recruited chronically stable HIV-infected individuals without diagnosis of diabetes mellitus at baseline (N = 62) to analyze the correlation of baseline inflammatory cytokines, including PAI-1 and whole-body insulin sensitivity, with 2-year follow-up, as measured by Matsuda Index. We found a negative correlation between baseline PAI-1 and Matsuda Index (r = -0.435, p = .001) and a negative correlation between baseline PAI-1 and Matsuda Index at 2 years (r = -0.377, p = .005). In a linear regression model that included age, total body fat mass percentage, serum amyloid A, and family history of diabetes mellitus, PAI-1 still remained significantly associated with Matsuda Index at 2-year follow-up (β = -.397, p = .002). Our longitudinal study suggests that PAI-1 is an independent predictor of impaired insulin sensitivity among chronic HIV-infected individuals.
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Kamonkiat
K
Wirunsawanya
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Loni
L
Belyea
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Cecilia
C
Shikuma
2 Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine of USC , Los Angeles, California.
Richard M
RM
Watanabe
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Lindsay
L
Kohorn
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Bruce
B
Shiramizu
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Brooks I
BI
Mitchell
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.|3 Queen's Medical Center , Honolulu, Hawaii.
Scott A
SA
Souza
4 Blood Systems Research Institute , San Francisco, California.
Sheila M
SM
Keating
4 Blood Systems Research Institute , San Francisco, California.|5 Department of Laboratory Medicine, University of California , San Francisco, California.|6 Department of Medicine, University of California , San Francisco, California.
Philip J
PJ
Norris
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.|7 Department of Tropical Medicine, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Lishomwa C
LC
Ndhlovu
1 Department of Medicine, Hawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine , Honolulu, Hawaii.
Dominic
D
Chow
D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*
D017395:Plasminogen Activator Inhibitor 1
chronic HIV infection; insulin sensitivity; plasminogen activator inhibitor-1