Integration of whole-body [18F]FDG PET/MRI with non-targeted metabolomics can provide new insights on tissue-specific insulin resistance in type 2 diabetes

Sci Rep. 2020 May 20;10(1):8343. doi: 10.1038/s41598-020-64524-0.


Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific phenotypes requires a multi-omics approach. In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body mass index, we calculated associations between parameters of whole-body positron emission tomography (PET)/magnetic resonance imaging (MRI) during hyperinsulinemic euglycemic clamp and non-targeted metabolomics profiling for subcutaneous adipose tissue (SAT) and plasma. Plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Visceral adipose tissue (VAT) and SAT insulin sensitivity (Ki), were positively associated with several lysophospholipids, while the opposite applied to branched-chain amino acids. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. Bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Furthermore, we detected several metabolites that were significantly higher in T2D than normal/prediabetes. In this study we present novel associations between several metabolites from SAT and plasma with the fat fraction, volume and insulin sensitivity of various tissues throughout the body, demonstrating the benefit of an integrative multi-omics approach.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acids, Branched-Chain / metabolism
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage
  • Fluorodeoxyglucose F18 / metabolism
  • Glucose Clamp Technique
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance*
  • Intra-Abdominal Fat / metabolism
  • Lipid Metabolism
  • Liver / metabolism
  • Lysophospholipids / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Metabolomics
  • Middle Aged
  • Multimodal Imaging / methods
  • Positron-Emission Tomography / methods
  • Prediabetic State / blood
  • Prediabetic State / diagnosis*
  • Prediabetic State / metabolism
  • Subcutaneous Fat / metabolism
  • Whole Body Imaging / methods*


  • Amino Acids, Branched-Chain
  • Insulin
  • Lysophospholipids
  • Fluorodeoxyglucose F18