Parent Metabolic Risk Factors Are Associated With Concurrent Nonalcoholic Fatty Liver Disease In Adolescent Offspring

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with features of the metabolic syndrome in individuals. Heritability of NAFLD has been described in first-degree relatives and in offspring of pre-pregnancy obese mothers. Methods: We examined associations between parent fasting glucose and lipid profile, and concurrent NAFLD in adolescent offspring from an established birth cohort. Community-based 17-year-old adolescents (n=1170) had liver ultrasound assessment for the presence and severity of hepatic steatosis. Anthropometric measurements were recorded in the adolescents, and fasting blood tests taken. Concurrently, fasting blood tests for glucose and lipids were obtained from 981 mothers and 708 fathers. Results: Adolescent liver ultrasound and parent blood tests were available on 979 adolescent-mother pairs and 706 adolescent-father pairs. NAFLD was diagnosed in 176 (15.2%) adolescents (19.6% female, 10.7% male) after exclusion of significant alcohol intake. Amongst mothers, 16.3%, 20.1% and 34.4% had raised plasma glucose, raised triglycerides (TG) or low high-density lipoprotein cholesterol (HDL-C) respectively. NAFLD was more common in adolescents in the presence of raised maternal fasting glucose (24.4% vs. 13.3%, p<0.001) or low HDL-C (19.9% vs. 12,6%, p=0.002) but not raised TG (17.8% vs. 14.5%, p=0.25). Adolescent NAFLD was associated with higher mean [SD] maternal plasma glucose (5.7[2.3] vs. 5.2[1.4]mmol/L, p<0.001), higher median [IQR] maternal TG (1.3 [0.9-1.7] vs. 1.1 [0.8-1.5]mmol/L, p=0.01) and lower maternal HDL-C (1.4 [0.4] vs. 1.5 [0.4]mmol/L, p=0.02). Maternal fasting glucose, TG and HDL-C were associated with the severity of hepatic steatosis (p<0.05). Paternal fasting glucose or lipids were not significantly associated with NAFLD in adolescent offspring (p>0.05). Records of maternal obesity during the 17-year assessment were not available, however maternal pre-pregnancy obesity 17 years earlier was associated with NAFLD in adolescent offspring (34.4% if obese vs. 14.2% if non-obese, p<0.001). Using multivariate analysis, raised maternal fasting glucose (OR 1.89, 95%CI 1.24-2.89, p=0.003) and low HDL-C (OR 1.56, 95%CI 1.09-2.25, p=0.02) were independently associated with NAFLD in adolescents. The association remained significant for maternal fasting glucose (OR 1.71, 95%CI 1.05-2.79, p=0.03) after adjusting for abdominal obesity in the adolescents. Conclusion: Maternal, but not paternal, fasting plasma glucose, triglycerides and HDL-C levels were associated with concurrent NAFLD in adolescent offspring. This study highlights the heritability of risk factors for NAFLD from maternal metabolic characteristics.