ASSOCIATIONS BETWEEN REMNANT LIPOPROTEIN CHOLESTEROL AND NONALCOHOLIC FATTY LIVER DISEASE IN ADOLESCENTS

Background: The incidence of nonalcoholic fatty liver disease (NAFLD) is rising in adolescents and young adults. NAFLD is a risk factor for incident cardiovascular disease. NAFLD is associated with obesity, insulin resistance and atherogenic dyslipidaemia (hypertriglyceridaemia, low serum levels of high density lipoprotein cholesterol [HDL‐C] and raised levels of low density lipoprotein [LDL‐C]). Remnant lipoprotein cholesterol (RLP‐C) is a novel risk factor for atherosclerotic cardiovascular disease that has recently been associated with increased risk of NAFLD. There is a paucity of data relating RLP‐C with NAFLD in adolescents. We aimed to (a) examine associations between RLP‐C and NAFLD and (b) determine if RLP‐C is an independent risk factor for NAFLD beyond insulin resistance in adolescents. Methods: Population‐based adolescents aged 17 years in the Raine Study (n=1170) participated in a cross‐sectional followup including health and lifestyle questionnaires and physical assessments. Abdominal ultrasound was used to examine the presence and severity of hepatic steatosis, abdominal subcutaneous adipose thickness (SAT) and visceral adipose thickness (VAT). Serum from fasting venous blood was tested for HDL‐C, triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), glucose, insulin, leptin and adiponectin. LDL‐C and homeostasis model assessment for insulin resistance (HOMA‐IR) were computed. RLP‐C was calculated as total cholesterol minus LDL‐C and HDL‐C. Presence of metabolic syndrome was determined. Results: NAFLD was diagnosed in 176/1170 (15.1%) adolescents. Adolescents with NAFLD had higher RLP‐C than adolescents without NAFLD (mean [SD] 0.55 [0.28] vs. 0.47 [0.24] mmol/L). RLP‐C levels increased with steatosis severity (Figure 1). RLP‐C was negatively correlated with serum adiponectin but positively correlated with serum leptin, insulin, hsCRP, ALT and GGT, systolic and diastolic BP, and all measures of general and subcutaneous adiposity (p<0.05 for all). Adolescents with RLP‐C in the top quartile had greater VAT and higher prevalence of metabolic syndrome than other adolescents (p<0.05). Using multivariate logistic regression analysis, adolescents with RLP‐C in the bottom quartile had a 70% lower likelihood of NAFLD compared with those with RLP‐C in the top quartile (OR 0.34, 95% CI 0.17‐0.70, p=0.003), after adjusting for waist circumference, sex, serum ALT, leptin, adiponectin (that were significantly associated with NAFLD, p<0.05 for all) and HOMA‐IR (non‐significant, p=0.35). This relationship persisted after further adjustment for serum total cholesterol, HDL‐C, LDL‐C and triglycerides. Conclusion: RLP‐C levels are strongly associated with NAFLD, VAT and metabolic syndrome, hence increased cardiometabolic risk in adolescents. The association of RLP‐C with NAFLD is independent of insulin resistance and obesity.