title: Insulin sensitivity and liver fat: role of iron load.
abstract: BACKGROUND
  Increased liver fat (LF) is associated with insulin resistance. However, a considerable individual variability between LF and insulin sensitivity (IS) is observed, and at equal levels of LF, insulin-resistant as well as insulin-sensitive individuals are found.
  
  
  OBJECTIVE
  Our objective was to study whether hepatic iron load (HIL) explains some of the variation between IS and LF.
  
  
  METHODS
  HIL was measured using a quantitative T2* magnetic resonance gradient echo imaging technique, and LF was measured by (1)H-magnetic resonance spectroscopy. Low T2* values indicate high HIL. We studied the association of LF and HIL with anthropometric data and IS. A total of 113 healthy nondiabetic subjects [69 females, 44 males; age 47 ± 1 yr; body mass index (BMI) = 28.9 ± 0.5 kg/m(2)] at increased risk for type 2 diabetes were included in the study.
  
  
  RESULTS
  T2* values adjusted for age negatively associated with serum ferritin levels (P < 0.0001) and positively associated with IS (P = 0.009). In addition, T2* values associated with LF (P = 0.008) but not with BMI (P = 0.6). In a multivariate model, IS adjusted for gender, age, and BMI was associated with T2* values (P = 0.015). IS adjusted for gender and age was independently associated with LF (P = 0.033) and T2* values (P = 0.004). In a stepwise regression analysis, LF explained 13.5% (P < 0.01) of the variation in IS, and HIL explained an additional 4.1% (P = 0.03).
  
  
  CONCLUSIONS
  HIL explains part of the variation between LF and IS. The mechanism by which iron load induces insulin resistance is possibly independent of the pathways involved in insulin resistance induced by fatty liver disease.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Eberhard-Karls-University Tübingen, D-72076 Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Haap
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.forename: Christine
authors.initials: C
authors.lastname: von Friedeburg
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.forename: Nina F
authors.initials: NF
authors.lastname: Schwenzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Claus
authors.initials: C
authors.lastname: Thamer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D015992:Body Mass Index; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005293:Ferritins; D007501:Iron