Dissertation committee:
Αναστασία Θανοπούλου, Επίκουρος Καθηγήτρια, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Σπήλιος Μανωλακόπουλος, Καθηγητής, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Δημήτρης Πεκτασίδης, Ομότιμος Καθηγητής, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Νικόλαος Τεντολούρης, Καθηγητής, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Αιμιλία Χατζηγιάννη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Αθανάσιος Ράπτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Ελένη Μπουτάτη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή Αθηνών, ΕΚΠΑ
Summary:
Background and Objectives
NAFLD is dramatically increasing in parallel with the pandemic of Type 2 Diabetes Mellitus. We investigated factors associated with Hepatic Steatosis (HS) in adult Greek individuals with established Type 2 Diabetes Mellitus. We also aimed to assess the performance of the most commonly used non-invasive blood-based biomarkers for liver fibrosis in the population above.
Materials and Methods
We investigated 120 consecutive people with Type 2 Diabetes attending the Diabetic Outpatient Clinic at an Academic Hospital in Athens, Greece. All of them had demographic, clinical and biochemical data recorded. HS was estimated by Magnetic Resonance Imaging determined by Proton Density Fat Fraction software (MRI-PDFF) and defined as the percentage of total liver fat divided by the liver volume. HS of >5% was considered abnormal. The PNPLA3 (I148M) variant was evaluated as a genetic factor by standard molecular techniques. FIBROMAX TM including SteatoTest for estimation of hepatic steatosis, ActiTest for estimation of hepatic necroinflammatory activity, NashTest2 for estimation of steatohepatitis and Fibrotest for estimation of hepatic fibrosis was also calculated. Liver Stiffness Measurement (LSM) was estimated by Two-Dimensional Shear Wave Elastography (2D SWE) (Supersonic Imagine, Aix-en-Provence, France). Apart from FIBROMAXTM, APRI Index, NAFLD Fibrosis score, BARD score, FIB-4 Index, ActiTest and NashTest2 were also calculated.
Results
Of the 120 participants, median age was 61,7, 46% were females, diabetes duration was 10 years and HbA1c was 6,7%. The median value of HS was 7,8. The PNPLA3 rs 738409 CC/CG/GG genotype frequencies were 54,2%, 35% and 10,8% respectively. In multivariate analysis, PNPLA3 rs 738409 (β=0,425, p=0,001), waist circumference (β=2,448, p=0,001) and female sex (β=0,419, p=0,002) had a direct association with hepatic steatosis, while duration of diabetes (β=-0,179, p=0,011) had an inverse association with hepatic steatosis. Only 16 subjects (14%) had LSM >8,0 kPa. Among Fibrosis biomarkers APRI score (p=0,001), NAFLD Fibrosis score (p=0,408), FIB-4 Index (p=0,658), BARD score (p=0,701), FibroTest (p=0,921), FibroTest was more indicative of the LSM values estimated with SWE. LSM (SWE) was directly correlated with both ActiTest (r=0.405, p≤0,001) and NashTest2 (r=0,299, p=0,002). According to linear regression, an increase of the ActiTest and NashTest 2 values increases the LSM values estimated with SWE by 5.632 times (p≤0,001, C.I. 3,213 – 8,051) and 3,981 times (p≤0.001, C.I. 2,398 – 5,563) respectively.
Conclusions
HS in Type 2 Diabetes is the sum of interplay of various factors exerting a direct or an inverse association, the most prominent among them being abdominal obesity and PNPLA3 molecular variability. Furthermore, people with Type 2 Diabetes Mellitus may require predictive models for hepatic fibrosis specifically developed for them. Extrapolation of results from non-diabetic population may result in misclassification.
