Ákos Nádasdi1, Viktor Gál2, Anikó Somogyi1, Gábor Firneisz13
1 2nd Department of Internal Medicine, Semmelweis University, Budapest
2 Brain Imaging Centre, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest
3 Molecular Medicine Research Group, Hungarian Academy of Sciences - Semmelweis University, Budapest
Introduction: NAFLD and T2DM are prevalent and closely associated to each other and to obesity, dyslipidaemia, IR, MetS. The PNPLA3 rs738409 G/G genotype is a risk factor for NAFLD development/progression.
Aims: We aimed to measure the intrahepatic (IHCL) and intrapancreatic lipid contents (IPCL) quantitatively and to assess the correlations with metabolic conditions in the view of PNPLA3 genotype data.
Method: 33 women with known PNPLA3 rs738409 genotypes (C/Cvs.G/G) and history of GDM (pGDM vs. pNGT) were recruited from the prior GDM EFSD-NH study. In the volunteers (mean age=37years, mean BMI=26,3kg/m2) IHCL and IPCL were measured with 1HMRS and CSI methods. 75g OGTT (0’-30’-120’) was performed, plasma glucose (PG), insulin-, liver-transaminase and HbA1C levels were assessed and anthropometric data were recorded.
The data were analysed in subgroups according to prior GDM (pGDM/pNGT n=18/15), PNPLA3rs738409 genotypes (CC/GG n=22/11). Additional analyses were performed by the OGTT results (IFG+IGT+DM/NGT: n=9/24) and by the presence of NAFLD (IHCL>5,5%, NAFLD/non-NAFLD n=9/24). Comparisons/correlations were done using T or MW-U/SRO tests.
Results: Women with G/G genotype (vs.C/C) had higher IHCL (median=10,1vs.3,4%, p=9,9*10-3), with pGDM (vs.pNGT) higher 120’PG (mean=7,1vs5,7mmol/l, p=0,049) levels (higher proportion of women had abnormal OGTT:6/18 vs. 3/15). In the NAFLD group (vs.non-NAFLD) the 30’/120’PG (mean=10,1vs7,5/8,1vs.5,8mmol/l, p=2*10-5/0,002, respectively) and HOMA2-IR (median=1,98vs.1,12, p=0,012), similarly in the abnormal OGTT (vs.NGT) group the IHCL (median=5,85vs.3,31%, p=0,018) and liver enzyme levels were higher. Correlations between BMI-IHCL, IHCL-PG (30’-120’), IHCL-HOMA2IR, IHCL-Uric acid, IHCL-TG and IHCL-IPCL were modified significantly by the PNPLA3 genotype.
Conclusion: Both the intrahepatic lipid deposition and the history of GDM had significant metabolic consequences. Although an abnormal OGTT is associated with the NAFLD, the track of correlations between the IHCL and metabolic markers are significantly modified by the PNPLA3 rs738409 genotype. The rs738409 gene variant influences the metabolic activity corresponding to a given degree of liver fat accumulation.
Doctoral School of Clinical Medicine
Program: 01 Study of Diabetes Mellitus, its comlications and the etiologic and genetic factors of hepatic diseases
Supervisor: Gábor Firneisz
E-mail adress: email@example.com