Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity.
OBJECTIVE
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.
Kotronen
Anna
A
Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 700, Room C425B, FIN-00029 HUCH, Helsinki, Finland. anna.kotronen@helsinki.fi
Lewitt
Moira
M
Hall
Kerstin
K
Brismar
Kerstin
K
Yki-Järvinen
Hannele
H
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D055105:Waist Circumference
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D008055:Lipids