New pathways in hepatic steatosis, insulin resistance, and type 2 diabetes

Koay YC1,2, Yang P3, Chen DL4, Jenkins AB4, Wood C5, Li M3, Greenfield JR4,6,7, Samocha-Bonet D4,6 and O'Sullivan JF1,2,8

  1. Sydney Medical School, The University of Sydney, Australia.
  2. Heart Research Institute, Sydney, Australia.
  3. School of Mathematics and Statistics, University of Sydney, Australia.
  4. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia.
  5. Talented Scientists Progam, School of Biomedical Science, The University of Sydney, Australia.
  6. Faculty of Medicine, UNSW, Australia.
  7. Department of Endocrinology and Diabetes Centre, St Vincent’s Hospital, Sydney, Australia.
  8. Royal Prince Alfred Hospital, Department of Cardiology, Sydney, Australia.

The global obesity epidemic, leading to non-alcoholic fatty liver disease (NAFLD) and Type 2 Diabetes (T2D), continues unabated despite sustained efforts to combat it, and is our greatest modern healthcare challenge. NAFLD is the commonest form of liver disease in the Western world, affecting one in three people in the general population, 90% of obese patients with type 2 diabetes (T2D), and 5.5 of 6 million Australians with liver disease – accounting for much of the $51 billion annual cost to our healthcare system. Although exact mechanisms remain unclear, accumulation of liver fat is a principal cause of T2D. We have recently discovered a new pathway in hepatic steatosis that independently predicts type 2 diabetes over 12 years in advance. Our subsequent work has revealed novel lipid biomarkers for NAFLD that can distinguish between liver insulin resistance and muscle insulin resistance. Three representative lipids alone can accurately classify patients according to the organ driving insulin resistance with >99% accuracy. We have also recently revealed how a common SNP (MAF.