High levels of tissue plasminogen activator (tPA) antigen precede the development of type 2 diabetes in a longitudinal population study. The Northern Sweden MONICA Study

Mats Ce Eliasson,Bernt Lindahl,Birgitta Stegmayr,Jan-Håkan Jansson

doi:10.1186/1475-2840-2-19

Mats Ce Eliasson, Bernt Lindahl + Show 2 more

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https://doi.org/10.1186/1475-2840-2-19

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Abstract

BackgroundImpaired fibrinolysis is found in impaired glucose tolerance and type 2 diabetes, associated with components of the metabolic syndrome. There are no data concerning fibrinolysis in subjects with normal glucose tolerance that convert to diabetes.MethodsWe studied the activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and the levels of tPA antigen (a marker of endothelial dysfunction) in 551 subjects with normal glucose tolerance in 1990 in relation to incident diabetes during nine years of follow-up.ResultsSubjects with diabetes at follow-up (n = 15) had significantly lower baseline tPA activity and higher PAI-1 activity and tPA antigen than non-converters. The risk of diabetes increased linearly across quartiles of PAI-activity (p = 0.007) and tPA antigen (p < 0.001) and decreased across quartiles of tPA activity (p = 0.026). The risk of diabetes with low tPA activity or high PAI-1 activity persisted after adjustment for age and sex but diminished to a non-significant level after further adjustments. The odds ratio of diabetes for high tPA antigen was 10.4 (95% confidence interval 2.7–40) adjusted for age and sex. After further adjustment for diastolic blood pressure, waist circumference, insulin, triglycerides, fasting and post load glucose the odds ratio was 6.5 (1.3–33, p = 0.024).ConclusionsImpaired fibrinolysis and endothelial dysfunction are evident in subjects with normal glucose tolerance who later develop diabetes. High tPA antigen is predictive of future diabetes independent from the metabolic syndrome.

Highlights

Impaired fibrinolysis is found in impaired glucose tolerance and type 2 diabetes, associated with components of the metabolic syndrome
Cardiovascular Diabetology 2003, 2 http://www.cardiab.com/content/2/1/19 glucose level as evident by the increased cardiovascular disease (CVD) risk already present with impaired glucose tolerance (IGT) [3,4]
As measured by tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activity, and a marker of endothelial dysfunction, as measured by tPA antigen, in a population sample with normal glucose tolerance at baseline and analysed data according to conversion to diabetes or not over nine years of follow-up

Summary

Introduction

Impaired fibrinolysis is found in impaired glucose tolerance and type 2 diabetes, associated with components of the metabolic syndrome. Glucose tolerance was classified according to WHO criteria from 1999 [23]: Recently, markers of inflammation, such as highly sensitive C-reactive protein, have been found to predict type 2 diabetes in long-time follow up of population samples, adjusting for measurements of obesity attenuates the relationship [8,9,10,11,12]. Such markers are weakly related to variables reflecting endothelial function such as adhesion molecules and von Willebrant factor [13]

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