PNPLA3 rs 738409 and Other Nongenetic Factors Associated with Hepatic Steatosis Estimated by Magnetic Resonance Imaging Proton Density Fat Fraction in Adult Greek Subjects with Type 2 Diabetes Mellitus

Objectives: Nonalcoholic fatty liver disease 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.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 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) was also calculated.Results: Of the 120 participants, median age was 61.7, 46% were females, diabetes duration was 10 years, and HbA1c (glycated hemoglobin) was 6.7%. The median value of HS was 7.8. The PNPLA3 rs738409 CC/CG/GG genotype frequencies were 54.2%, 35%, and 10.8%, respectively. In multivariate analysis, PNPLA3 rs738409 (beta = 0.425, P = 0.001), waist circumference (beta = 2.448, P = 0.001), and female sex (beta = 0.419, P = 0.002) had a direct association with HS, while duration of diabetes (beta = -0.179, P = 0.011) had an inverse association with HS.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.