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Insulin Resistance Is Unrelated to Circulating Retinol Binding Protein and Protein C Inhibitor

Department of Internal Medicine III (M.P., M.K., A.L., M.G.B., P.N., C.A.), Division of Endocrinology and Metabolism, Clinical Institute of Medical and Chemical Laboratory Diagnostics (J.T., O.W., H.E.), and Department of Clinical Pharmacology (C.A.), Medical University of Vienna, A-1090 Vienna, Austria

Address all correspondence and requests for reprints to: Michael Krebs, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: michael.krebs{at}meduniwien ac.at; or Harald Esterbauer, M.D, Ph.D., Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: harald.esterbauer{at}meduniwien.ac.at.

Context: Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant.

Objective: The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen.

Design and Setting: This was a clinical study.

Patients: Nondiabetic humans with high (IS; n = 20, 14 females, six males, aged 47.2 ± 1.9 yr, body mass index 26 ± 1 kg/m²) and low (IR; n = 20, 14 females, six males, aged 45.5 ± 1.7 yr, body mass index 28 ± 1 kg/m²) insulin-stimulated glucose-disposal (M) participated in this study.

Main Outcome Measures: M was measured by 2-h hyperinsulinemic (40 mU·min^–1·m^–2)-isoglycemic clamp tests. Measurements of RBP were performed using a nephelometric method and validated using quantitative Western blotting.

Results: M (80–120 min) was higher in IS (10.9 ± 0.6 mg·min^–1·kg^–1) than IR (4.0 ± 0.2; P < 10^–12). Fasting plasma RBP concentrations were comparable between IS and IR measured by both nephelometry (IS: 4.4 ± 0.3; IR: 4.6 ± 0.3 mg/dl, P = 0.6) and quantitative Western blot (IS 7.9 ± 0.5, IR 8.3 ± 0.6 mg/dl; P = 0.6). Fasting plasma PCI active antigen was similar in both groups. Plasma RBP and PCI were not significantly related to M. RBP was positively correlated with uric acid (r = 0.488, P = 0.003), triglycerides (r = 0.592, P < 0.001), prealbumin (r = 0.63, P < 0.0001), and vitamin A (r = 0.75, P < 10^–6).

Conclusions: Our data demonstrate that healthy, insulin-resistant humans do not show altered plasma retinol binding factors, such as RBP and PCI. Both do not significantly correlate with insulin sensitivity. Thus, our findings do not support the hypothesis of insulin sensitivity modulation by proteins involved in retinol transport.

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