Diabetes Metab J.  2019 Oct;43(5):700-710. 10.4093/dmj.2018.0201.

Severity of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus: Relationship between Nongenetic Factors and PNPLA3/HSD17B13 Polymorphisms

• Bellan M
• Colletta C
• Barbaglia
• Salmi L
• Clerici R
• Mallela VR
• Castello L
• Saglietti
• Carnevale Schianca GP
• Minisini R
• Pirisi M

• KMID: 2460962
• DOI: http://doi.org/10.4093/dmj.2018.0201

Abstract

BACKGROUND
The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is high, though its severity is often underestimated. Our aim is to provide an estimate of the prevalence of severe NAFLD in T2DM and identify its major predictors.
METHODS
T2DM patients (n=328) not previously known to have NAFLD underwent clinical assessment, transient elastography with measure of liver stiffness (LS) and controlled attenuation parameter (CAP), and genotyping for patatin like phospholipase domain containing 3 (PNPLA3) and 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13).
RESULTS
Median LS was 6.1 kPa (4.9 to 8.6). More than one-fourth patients had advanced liver disease, defined as LS ≥7.9 kPa (n=94/238, 29%), and had a higher body mass index (BMI) than those with a LS <7.9 kPa. Carriage of the G allele in the PNPLA3 gene was associated with higher LS, being 5.9 kPa (4.7 to 7.7) in C/C homozygotes, 6.1 kPa (5.2 to 8.7) in C/G heterozygotes, and 6.8 kPa (5.8 to 9.2) in G/G homozygotes (P=0.01). This trend was absent in patients with ≥1 mutated HSD17B13 allele. In a multiple linear regression model, BMI and PNPLA3 genotype predicted LS, while age, gender, disease duration, and glycosylated hemoglobin did not fit into the model. None of these variables was confirmed to be predictive among carriers of at least one HSD17B13 mutated allele. There was no association between CAP and polymorphisms of PNPLA3 or HSD17B13.
CONCLUSION
Advanced NAFLD is common among T2DM patients. LS is predicted by both BMI and PNPLA3 polymorphism, the effect of the latter being modulated by mutated HSD17B13.

Keyword

Adiponutrin; Body mass index; Diabetes mellitus, type 2; Fibrosis; Non-alcoholic fatty liver disease

MeSH Terms

Alleles
Body Mass Index
Diabetes Mellitus*
Diabetes Mellitus, Type 2
Elasticity Imaging Techniques
Fibrosis
Genotype
Hemoglobin A, Glycosylated
Heterozygote
Homozygote
Humans
Linear Models
Liver
Liver Diseases
Non-alcoholic Fatty Liver Disease*
Phospholipases
Prevalence
Phospholipases

Figure

• 

  Fig. 1 Liver stiffness (kPa) distribution based on patatin like phospholipase domain containing 3 (PNPLA3) genotypes. Columns indicate medians, error bars interquartile ranges.

• 

  Fig. 2 Liver stiffness (kPa) distribution among patatin like phospholipase domain containing 3 (PNPLA3) genotypes among 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13) (A) wild type and (B) mutated carriers. Columns indicate medians, error bars interquartile ranges. HSD17B13 T/T (wild type), HSD17B13 TA/* (heterozygous and/or homozygous “A” insertional mutation).

• 

  Fig. 3 Predicted values of liver stiffness (LS) (kPa), based on patatin like phospholipase domain containing 3 (PNPLA3) genotype and body mass index (BMI). Error bars indicate 95% confidence intervals. The upper horizontal dotted line indicates LS value suggestive of cirrhosis, the lower one the value suggestive of absent or minimal fibrosis.

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