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

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Abstract

Background

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.

Aim

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).

Methods

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).

Results

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).

Conclusions

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.

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Abbreviations

LFC:

Liver fat content

BMI:

Body mass index

T2DM:

Type 2 diabetes mellitus

HA:

Hyaluronic acid

P3NP:

Procollagen III N-terminal peptide

TIMP-1:

Tissue inhibitor metalloproteinase-1

ALT:

Alanine aminotransferase

HV:

Healthy volunteers

NAFLD:

Nonalcoholic fatty liver disease

1H MRS:

Magnetic resonance spectroscopy

MR:

Magnetic resonance

TG:

Triglyceride

FFA:

Free fatty acid

THRIVE:

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

TFE:

Turbo field echo

PRESS:

Point resolved spectroscopy

TE/TR:

Echo time for PRESS sequence/repetition time

GGT:

Gamma-glutamyl transpeptidase

ALP:

Alkaline phosphatase

Bil:

Bilirubin

HDL-cholesterol:

High density lipoprotein-cholesterol

LDL-c:

Low density lipoprotein-cholesterol

IL:

Interleukin

MCP-1:

Monocyte chemoattractant

TNFα:

Tumor necrosis factor alpha

TGFβ:

Transforming growth factor-beta

HbA1c:

Glycated hemoglobin A1c

HOMA-IR:

Homeostatic model assessment

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 10, Singapore, 119228, Singapore

    E. Y. H. Khoo

  2. Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, UK

    M. C. Stevenson, E. Leverton & P. G. Morris

  3. iQur Ltd, Southampton, UK

    R. Cross

  4. AstraZeneca R&D, Mölndal, Sweden

    J. W. Eriksson

  5. Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

    J. W. Eriksson

  6. Discovery Department, Astrazeneca Pharmaceuticals, Macclesfield, UK

    S. M. Poucher

  7. School of Biomedical Sciences, University of Nottingham, Nottingham, UK

    I. Spendlove, I. A. Macdonald & P. Mansell

  8. Department of Diabetes and Endocrinology, Nottingham University Hospitals, Nottingham, UK

    P. Mansell

  9. National Institute for Health Research Biomedical Unit, Nottingham University Hospitals, Nottingham, UK

    G. P. Aithal

Authors
  1. E. Y. H. Khoo
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  2. M. C. Stevenson
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  3. E. Leverton
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  4. R. Cross
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  5. J. W. Eriksson
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  6. S. M. Poucher
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  7. I. Spendlove
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  8. P. G. Morris
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  9. I. A. Macdonald
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  10. P. Mansell
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  11. G. P. Aithal
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Corresponding author

Correspondence to E. Y. H. Khoo.

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Khoo, E.Y.H., Stevenson, M.C., Leverton, E. et al. Elevation of Alanine Transaminase and Markers of Liver Fibrosis After a Mixed Meal Challenge in Individuals with Type 2 Diabetes. Dig Dis Sci 57, 3017–3025 (2012). https://doi.org/10.1007/s10620-012-2219-z

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  • DOI: https://doi.org/10.1007/s10620-012-2219-z

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