Insulin resistance and NAFLD: Relationship with intrahepatic iron and serum TNF-α using 1H MR spectroscopy and MRI

Diabetes Metab. 2019 Oct;45(5):473-479. doi: 10.1016/j.diabet.2019.01.005. Epub 2019 Jan 17.


Aim: The association of non-alcoholic fatty liver disease (NAFLD) with insulin resistance (IR) is well established, yet little is known of their possible relationship with intrahepatic iron and serum tumour necrosis factor (TNF)-α concentrations in adults without diabetes. Thus, this study looked at the relationship of intrahepatic iron and serum TNF-α with intrahepatic triglycerides and IR in non-diabetic adults.

Methods: In this cross-sectional study of 104 healthy non-diabetic Caucasians, a quantitative magnetic resonance (MR) imaging T2 gradient-echo technique was used to measure hepatic iron, with 1H-MR spectroscopy used to measure hepatic triglycerides. HOMA-IR was calculated to determine IR.

Results: The prevalence of hepatic iron overload (HIOL) was 26.6% in individuals with NAFLD vs. 0% in those without. IR was present in 87.5% of subjects with both NAFLD and HIOL, in 45.4% of those with NAFLD but not HIOL, and in 4.5% of those with neither. HOMA-IR was positively correlated with hepatic triglycerides (r = 0.56, P < 0.001) and hepatic iron (r = 0.52, P < 0.001), whereas serum TNF-α concentrations correlated with intrahepatic triglyceride levels (r = 0.28, P < 0.04), but not with intrahepatic iron. Hepatic triglycerides, serum TNF-α and age were the only significant determinants of IR in regression analyses.

Conclusion: IR is closely associated with intrahepatic triglycerides and, to a lesser extent, intrahepatic iron, with some interplay between them. High serum TNF-α concentrations may contribute to the association between NAFLD and IR, while increased hepatic triglycerides appear to be a determinant of the development of HIOL in non-diabetic subjects without haemochromatosis.

Keywords: Hepatic iron; Insulin resistance; NAFLD; TNF-α.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Cross-Sectional Studies
  • Female
  • Humans
  • Insulin Resistance / physiology*
  • Iron / analysis*
  • Liver / diagnostic imaging*
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / diagnostic imaging
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / blood*


  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Iron