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Association of Inflammation Markers with Impaired Insulin Sensitivity and Coagulative Activation in Obese Healthy Women

Departments of Medicine and Aging (M.T.G., A.F., M.M., M.R.M., G.D.) and Biomedical Sciences (M.R.), University of Chieti "G. D’Annunzio," School of Medicine, 66013 Chieti; Metabolic Unit (G.P.), Institute of Biomedical Engineering (ISIB-CNR), 35127 Padova; Department of Medicine (S.V.), University of Palermo, 90128 Palermo; and University of Rome "La Sapienza" (S.B.), 00161 Rome, Italy

Address all correspondence and requests for reprints to: Giovanni Davì, M.D., Department of Medicine and Aging, School of Medicine, University of Chieti "G. D’Annunzio," Via Colle dell’Ara, 66013 Chieti, Italy. E-mail: gdavi{at}unich.it.

Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-ß1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-ß1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-ß1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-ß1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-ß1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-ß1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.

This work was supported by grants from the Italian Ministry of Research and Education (Cofin 2002, and Center of Excellence on Aging).

No conflict of interest exists in connection with this article.

Abbreviations: BMI, Body mass index; CRP, C-reactive protein; F1 + 2, prothrombin fragment 1 + 2; factor VIIa, activated factor VIIa; FSIGT, frequently sampled iv glucose tolerance test; H, Kruskal-Wallis method; IIS, impaired insulin sensitivity; NIS, normal insulin sensitivity; PAI-1, plasminogen activator inhibitor-1; S_I, insulin sensitivity index; TF, tissue factor; WHR, waist to hip ratio.

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