High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels

J Clin Endocrinol Metab. 2015 Jun;100(6):2231-8. doi: 10.1210/jc.2015-1966. Epub 2015 Apr 17.


Context and objective: Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile.

Participants and methods: We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA).

Results: The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01).

Conclusions: The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Fatty Liver / blood
  • Fatty Liver / complications
  • Fatty Liver / epidemiology
  • Female
  • Humans
  • Insulin Resistance / physiology
  • Liver / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / epidemiology*
  • Obesity / blood
  • Obesity / complications
  • Obesity / epidemiology
  • Prevalence
  • Transaminases / blood*
  • Triglycerides / metabolism


  • Triglycerides
  • Transaminases