Digestive Diseases and Sciences

, Volume 57, Issue 11, pp 3017–3025 | Cite as

Elevation of Alanine Transaminase and Markers of Liver Fibrosis After a Mixed Meal Challenge in Individuals with Type 2 Diabetes

  • E. Y. H. KhooEmail author
  • M. C. Stevenson
  • E. Leverton
  • R. Cross
  • J. W. Eriksson
  • S. M. Poucher
  • I. Spendlove
  • P. G. Morris
  • I. A. Macdonald
  • P. Mansell
  • G. P. Aithal
Original Article



Hyperalimentation for 4 weeks is associated with raised liver enzymes and liver fat content (LFC), which are two common features found in individuals with diabetes.


We evaluated the effect of two mixed meal challenges on LFC, liver enzymes and serum bio-markers of liver injury and fibrosis in 16 healthy volunteers (HV) and subjects with type 2 diabetes (T2DM).


Subjects (HV: 9 male, 7 female, aged 57.9 ± 1.7 years, body mass index (BMI) 27.1 kg/m2; and T2DM: 11 male, 5 female, aged 62.1 ± 1.3 years, BMI 28.0 ± 0.4 kg/m2) consumed two meals at 1 h (884 kcal) and at 6 h (1,096 kcal). LFC determined by 1H magnetic resonance spectroscopy, serum levels of liver enzymes, hyaluronic acid (HA), procollagen III N-terminal peptide (P3NP) and tissue inhibitor metalloproteinase-1 (TIMP-1) were estimated at time 0 (fasting) and 9 h (postprandial).


Fasting LFC was higher in the T2DM group 7.6 % (4.9, 15.4) [median (inter-quartile range)] than in the HV group 2.3 % (0.8, 5.1) (p < 0.05) while levels of HA, P3NP and TIMP-1 were similar. Following the meal challenge there was no significant change in LFC. Subjects with T2DM had higher post-prandial rise in alanine transaminase (ALT) (p = 0.014), serum HA (p = 0.007) and P3NP (p = 0.015) compared with HV. Fasting LFC correlated with a greater post-prandial increase in P3NP levels in all subjects (Pearson correlation r = 0.53, p = 0.001).


In subjects with T2DM, a mixed meal challenge is associated with a significant elevation in the serum levels of ALT, HA and P3NP without significant changes in LFC. These markers should be performed in the fasted state.


Diabetes mellitus Hyper-alimentation Liver fat content Liver fibrosis Magnetic resonance spectroscopy Obesity 



Liver fat content


Body mass index


Type 2 diabetes mellitus


Hyaluronic acid


Procollagen III N-terminal peptide


Tissue inhibitor metalloproteinase-1


Alanine aminotransferase


Healthy volunteers


Nonalcoholic fatty liver disease


Magnetic resonance spectroscopy


Magnetic resonance




Free fatty acid


T-1 (weighted) high resolution isotropic volume excitation image


Turbo field echo


Point resolved spectroscopy


Echo time for PRESS sequence/repetition time


Gamma-glutamyl transpeptidase


Alkaline phosphatase




High density lipoprotein-cholesterol


Low density lipoprotein-cholesterol




Monocyte chemoattractant


Tumor necrosis factor alpha


Transforming growth factor-beta


Glycated hemoglobin A1c


Homeostatic model assessment



This work was supported by AstraZeneca, Europe. The study was investigator led and the authors had complete independence from the funder.

Conflict of interest

RC is an employee of iQur Ltd and his role was the analysis of serum HA, amino-terminal P3NP, and TIMP-1 as well as editing the manuscript. JWE and SMP are employees of Astrazeneca, Europe.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • E. Y. H. Khoo
    • 1
    Email author
  • M. C. Stevenson
    • 2
  • E. Leverton
    • 2
  • R. Cross
    • 3
  • J. W. Eriksson
    • 4
    • 5
  • S. M. Poucher
    • 6
  • I. Spendlove
    • 7
  • P. G. Morris
    • 2
  • I. A. Macdonald
    • 7
  • P. Mansell
    • 7
    • 8
  • G. P. Aithal
    • 9
  1. 1.Division of Endocrinology, Department of Medicine, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  2. 2.Sir Peter Mansfield Magnetic Resonance CentreUniversity of NottinghamNottinghamUK
  3. 3.iQur LtdSouthamptonUK
  4. 4.AstraZeneca R&DMölndalSweden
  5. 5.Institute of MedicineSahlgrenska University HospitalGothenburgSweden
  6. 6.Discovery DepartmentAstrazeneca PharmaceuticalsMacclesfieldUK
  7. 7.School of Biomedical SciencesUniversity of NottinghamNottinghamUK
  8. 8.Department of Diabetes and EndocrinologyNottingham University HospitalsNottinghamUK
  9. 9.National Institute for Health Research Biomedical UnitNottingham University HospitalsNottinghamUK

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