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Insulin-Like Growth Factor Binding Protein 1 as a Novel Specific Marker of Hepatic Insulin Sensitivity

Department of Medicine (A.K., H.Y.-J.), Division of Diabetes, University of Helsinki, FIN-00029 Helsinki, Finland; Minerva Medical Research Institute (A.K.), FIN-00029 Helsinki, Finland; and The Rolf Luft Research Center for Diabetes and Endocrinology (M.L., K.H., K.B.), Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden

Address all correspondence and requests for reprints to: Anna Kotronen, M.B., Ph.D., Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 700, Room C425B, FIN-00029 HUCH, Helsinki, Finland. E-mail: anna.kotronen{at}helsinki.fi.

Background and Aims: The liver is the main source and insulin the main regulator of IGF binding protein 1 (IGFBP-1) in humans. Here we examined how serum IGFBP-1 concentrations are related to directly measured hepatic insulin sensitivity and liver fat content in humans.

Methods: We measured fasting serum (fS) IGFBP-1 concentrations and liver fat content by proton magnetic resonance spectroscopy in 113 nondiabetic subjects. In addition, hepatic insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp (insulin 0.3 mU/kg·min) technique in combination with the infusion of [3-(3)H]glucose in 78 subjects.

Results: fS-IGFBP-1 concentrations were inversely related to liver fat content (r = –0.38, P < 0.0001). Of circulating parameters, fS-IGFBP-1 was better correlated to hepatic insulin sensitivity (r = 0.48, P < 0.0001) than fS-insulin (r = –0.42, P = 0.0001), fS-C-peptide (r = –0.41, P = 0.0002), fS-triglyceride (r = –0.33, P = 0.003), or fS-high-density lipoprotein cholesterol (r = 0.30, P = 0.007). In multiple linear regression analyses, body mass index (P < 0.0001) and fS-IGFBP-1 (P = 0.008), but neither age nor gender, were independently associated with hepatic insulin sensitivity (P < 0.0001 for ANOVA). Neither fS-insulin nor fS-C-peptide were independent determinants of hepatic insulin sensitivity after adjusting for age, gender, and body mass index.

Conclusions: fS-IGFBP-1 is inversely correlated with liver fat and is an obesity-independent and liver-specific circulating marker of hepatic insulin sensitivity.

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