https://doi.org/10.1177/1479164117703034
Diabetes & Vascular Disease Research
2017, Vol. 14(4) 345–352
© The Author(s) 2017
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DOI: 10.1177/1479164117703034
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Introduction
Endothelial-derived fibrinolytic factors such as plasmino-
gen activator inhibitor-1 (PAI-1) antigen, tissue plasmi-
nogen activator antigen (tPAag), tissue plasminogen
activator/plasminogen activator inhibitor-1 (tPA/PAI-1)
complex and the haemostatic factor, von Willebrand factor
(vWF), are known predictors of myocardial infarction and
stroke.
1–4
They are also related to dysglycaemia. Thus,
PAI-1 levels are correlated with the levels of glucose,
5–7
and PAI-1, tPAag and vWF all predict type 2 diabetes.
8
The effect of basal insulin glargine on the
fibrinolytic system and von Willebrand
factor in people with dysglycaemia and
high risk for cardiovascular events: Swedish
substudy of the Outcome Reduction with
an Initial Glargine Intervention trial
Aslak Rautio
1,2
, Kurt Boman
1,3
, Hertzel C Gerstein
4
,
Jenny Hernestål-Boman
1,3
, Shun Fu Lee
4
, Mona Olofsson
1,3
and Linda Garcia Mellbin
5
Abstract
Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen
activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of
cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization
with insulin glargine might improve the levels of these factors.
Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.
gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen
activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand
factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years).
Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the
insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied
fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences
in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole
study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen
activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in
the insulin glargine but not in the standard care group.
Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels
of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.
Keywords
Diabetes, insulin glargine, glucose-lowering treatment, fibrinolysis
1
Department of Public Health and Clinical Medicine, Umeå University,
Umeå, Sweden
2
Department of Medicine, Sunderby Hospital, Luleå, Sweden
3
Research Unit, Skellefteå Hospital, Skellefteå, Sweden
4
Population Health Research Institute, Hamilton Health Sciences and
McMaster University, Hamilton, ON, Canada
5
Unit of Cardiology, Department of Medicine, Solna, Karolinska
Institutet, Stockholm, Sweden
Corresponding author:
Aslak Rautio, Department of Medicine, Sunderby Hospital, 971 80
Luleå, Sweden.
Email: aslak.rautio@nll.se
0010.1177/1479164117703034Diabetes & Vascular Disease ResearchRautio et al.
research-article 2017
Original Article