Liver Fat and Cardiometabolic Risk Factors Among School‐Age Children

Abstract

Background and Aims Nonalcoholic fatty liver disease is a major risk factor for cardiometabolic disease in adults. The burden of liver fat and associated cardiometabolic risk factors in healthy children is unknown. In a population‐based prospective cohort study among 3,170 10‐year‐old children, we assessed whether both liver fat accumulation across the full range and nonalcoholic fatty liver disease are associated with cardiometabolic risk factors already in childhood. Approach and Results Liver fat fraction was measured by magnetic resonance imaging, and nonalcoholic fatty liver disease was defined as liver fat fraction ≥5.0%. We measured body mass index, blood pressure, and insulin, glucose, lipids, and C‐reactive protein concentrations. Cardiometabolic clustering was defined as having three or more risk factors out of high visceral fat mass, high blood pressure, low high‐density‐lipoprotein cholesterol or high triglycerides, and high insulin concentrations. Nonalcoholic fatty liver disease prevalences were 1.0%, 9.1%, and 25.0% among children who were normal weight, overweight, and obese, respectively. Both higher liver fat within the normal range (<5.0% liver fat) and nonalcoholic fatty liver disease were associated with higher blood pressure, insulin resistance, total cholesterol, triglycerides, and C‐reactive protein concentrations ( P values < 0.05). As compared with children with <2.0% liver fat, children with ≥5.0% liver fat had the highest odds of cardiometabolic clustering (odds ratio 24.43 [95% confidence interval 12.25, 48.60]). The associations remained similar after adjustment for body mass index and tended to be stronger in children who were overweight and obese. Conclusions Higher liver fat is, across the full range and independently of body mass index, associated with an adverse cardiometabolic risk profile already in childhood. Future preventive strategies focused on improving cardiometabolic outcomes in later life may need to target liver fat development in childhood.

Inulin Exerts Beneficial Effects on Non-Alcoholic Fatty Liver Disease via Modulating gut Microbiome and Suppressing the Lipopolysaccharide-Toll-Like Receptor 4-Mψ-Nuclear Factor-κB-Nod-Like Receptor Protein 3 Pathway via gut-Liver Axis in Mice

“…NAFLD represents a disease characterized by hepatocyte steatosis and excessive fat accumulation without abnormal alcohol intake ( Ekstedt et al, 2017 ). NAFLD contributes to increasing the risk of cirrhosis and hepatocellular carcinoma (HCC) ( Kanwal et al, 2018 ), and also closely relates to the progression of cardiovascular diseases, type 2 diabetes and other metabolic diseases ( Geurtsen et al, 2019 ), developing to a major health problem with limited treatment options. Thus, novel strategies for the control of NAFLD are urgently needed.…”

Associations Between Intake of Sugar‐Containing Beverages in Infancy With Liver Fat Accumulation at School Age

“…( 36 ) Because we observed a statistically significant interaction between sugar‐containing beverage intake in infancy with maternal education and childhood BMI, we performed additional stratified analyses. ( 12,36 ) We did not observe a statistically significant interaction between sugar‐containing beverage intake in infancy with child sex. ( 3,35 ) As sensitivity analyses, we first repeated the confounder model with sugar‐containing beverage intake standardized for total daily energy intake using the residual method and without adjustment for total daily energy intake as a confounder, as energy standardization could possibly reduce the measurement error.…”

“…( 40 ) Using data from the same cohort as the current study, we recently reported associations of liver fat across the full spectrum with risk factors for cardiometabolic disease already at 10 years. ( 12 ) Dietary patterns in infancy have been shown to track into adulthood. ( 39 ) Early lifestyle exposures are suggested to contribute to the development of not only obesity but also liver fat accumulation and NAFLD.…”

“…(11) We have recently reported associations between liver fat across the full spectrum and risk factors for cardiometabolic disease at school age. (12) Early life exposures may contribute to the development of not only obesity but also of liver fat accumulation and NAFLD. (11,13,14) It is not known whether sugar-containing beverage intake in infancy leads to a higher risk of liver fat accumulation and subsequent NAFLD later in life.…”

High prevalence of elevated serum liver enzymes in Chinese children suggests metabolic syndrome as a common risk factor

“…The liver is the major metabolic organ in the human body, and a healthy liver is critical for children's development as well as for the prevention of future risk of cardiovascular disease and other metabolic disorders. 1 However, abnormal liver function tests, i.e. increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), are commonly seen in paediatric clinics in China.…”