Elevation of Alanine Transaminase and Markers of Liver Fibrosis After a Mixed Meal Challenge in Individuals with Type 2 Diabetes
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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.
KeywordsDiabetes mellitus Hyper-alimentation Liver fat content Liver fibrosis Magnetic resonance spectroscopy Obesity
Liver fat content
Body mass index
Type 2 diabetes mellitus
Procollagen III N-terminal peptide
Tissue inhibitor metalloproteinase-1
Nonalcoholic fatty liver disease
- 1H MRS
Magnetic resonance spectroscopy
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
High density lipoprotein-cholesterol
Low density lipoprotein-cholesterol
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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