title: Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies.
abstract: An emerging body of evidence has implicated plasminogen activator inhibitor-1 (PAI-1) in the development of type 2 diabetes (T2D), though findings have not always been consistent. We systematically reviewed epidemiological studies examining the association of PAI-1 with T2D. EMBASE, PubMed, Web of Science, and the Cochrane Library were searched to identify studies for inclusion. Fifty-two studies (44 cross-sectional with 47 unique analytical comparisons and 8 prospective) were included. In pooled random-effects analyses of prospective studies, a comparison of the top third vs. bottom third of baseline PAI-1 values generated a RR of T2D of 1.67 (95% CI 1.28-2.18) with moderate heterogeneity (I(2) = 38%). Additionally, of 47 cross-sectional comparisons, 34(72%) reported significantly elevated PAI-1 among diabetes cases versus controls, 2(4%) reported significantly elevated PAI-1 among controls, and 11(24%) reported null effects. Results from pooled analyses of prospective studies did not differ substantially by study design, length of follow-up, adjustment for various putative confounding factors, or study quality, and were robust to sensitivity analyses. Findings from this systematic review of the available epidemiological literature support a link between PAI-1 and T2D, independent of established diabetes risk factors. Given the moderate size of the association and heterogeneity across studies, future prospective studies are warranted.
authors.affiliation: Postgraduate Program in Epidemiology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: James
authors.initials: J
authors.lastname: Yarmolinsky
authors.affiliation: Postgraduate Program in Epidemiology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Bordin Barbieri
authors.affiliation: Occupational and Environmental Epidemiology &NetTeaching Unit, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weinmann
authors.affiliation: Postgraduate Program in Epidemiology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Statistics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Ziegelmann
authors.affiliation: Postgraduate Program in Epidemiology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Duncan
authors.affiliation: Postgraduate Program in Epidemiology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Maria
authors.initials: M
authors.lastname: Inês Schmidt
mesh_terms: D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D017395:Plasminogen Activator Inhibitor 1
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