Fibrinolytic dysfunction in insulin-resistant women with previous gestational diabetes

Authors


  • Department of Internal Medicine III, Division of Endocrinology and Metabolism (S. Farhan, W. Waldhäusl, A. Kautzky-Willer), Department of Internal Medicine III, Division of Nephrology (C. Winzer), and Institute for Medical Laboratory Diagnostics (P. Quehenberger, C. Bieglmaier, O. F. Wagner), Medical University of Vienna; Department of Cardiology and Emergency Medicine, Wilhelminen Hospital Vienna (S. Farhan, K. Huber), Vienna, Austria; Metabolic Unit, Institute of Biomedical Engineering, National Research Council (ISIB-CNR), Padova, Italy (A. Tura, G. Pacini).

Alexandra Kautzky-Willer, MD, Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Währinger Gürtel 18–20, A-1090, Vienna, Austria. Tel.: +43 1 40400 2126; fax: +43 1 40400 5740; e-mail: alexandra.kautzky-willer@meduniwien.ac.at

Abstract

Background  Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease.

Materials and methods  Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% (n = 37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems.

Results  Women with p-GDM and IIS had significantly increased body fat mass (BFM) (P ≤ 0·001) compared with women with p-GDM and NIS and controls, whereas the waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared with the controls (P ≤ 0·001). Mean PAI-1 and t-PA as well as fasting and stimulated plasma concentrations of proinsulin, C-peptide and insulin were elevated, whereas the disposition index was lower in women with p-GDM and IIS compared with women with p-GDM and NIS and the controls (P < 0·001). Plasma levels of fibrinogen and vWF did not differ between the groups. Obese women with IIS had higher PAI-1 levels than lean women with IIS (P ≤ 0·001). PAI-1 inversely correlated with the insulin sensitivity index (SI) but only in women with IIS (P < 0·0001). On regression analysis, only fasting proinsulin and WHR remained significant independent predictors of PAI-1 elevation in IIS (P ≤ 0·0001 and P ≤ 0·001). The PAI-1/SI ratio was elevated in women with IIS independently of their glucose tolerance status (P < 0·001 vs. NIS and controls).

Conclusions  Plasminogen activator inhibitor type 1 is elevated in p-GDM women with IIS and depends on plasma proinsulin and abdominal obesity. An increase of the PAI-1/SI ratio further characterizes obese insulin-resistant p-GDM women who may be at risk for diabetes and angiopathy.

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