Hepatic Fat in Early Childhood Is Independently Associated With Estimated Insulin Resistance: The Healthy Start Study

J Clin Endocrinol Metab. 2021 Oct 21;106(11):3140-3150. doi: 10.1210/clinem/dgab541.


Background: Fatty liver disease is a common metabolic abnormality in adolescents with obesity but remains understudied in early childhood.

Objectives: To describe hepatic fat deposition in prepubertal children and examine cross-sectional associations with metabolic markers and body composition.

Methods: Data were from 286 children ages 4 to 8 years old in the Healthy Start Study, a longitudinal prebirth cohort in Colorado (USA). Assessments included magnetic resonance imaging to quantify hepatic and abdominal fats, fasting blood draws to measure metabolic markers, and air displacement plethysmography to measure body composition (fat mass and fat-free mass).

Results: The median (interquartile range) for hepatic fat was 1.65% (1.24%, 2.11%). Log-transformed hepatic fat was higher in Hispanic [mean (95% CI): 0.63 (0.52, 0.74)] vs non-Hispanic white children [0.46 (0.38, 0.53), P = 0.01] and children with overweight/obesity [0.64 (0.49, 0.79)] vs normal-weight [0.47 (0.40, 0.53), P = 0.02]. Higher log-hepatic fat was associated with higher insulin [β (95% CI): 1.47 (0.61, 2.33) uIU/mL, P = 0.001] and estimated insulin resistance (homeostatic model assessment) [0.40 (0.20, 0.60), P < 0.001] in the full sample and glucose [5.53 (2.84, 8.21) mg/dL, P < 0.001] and triglycerides [10.92 (2.92,18.91) mg/dL, P = 0.008] in boys, in linear regression models adjusted for sociodemographics, maternal/perinatal confounders, and percentage body fat. Log-hepatic fat was also associated with abdominal subcutaneous adipose tissue [SAT; 7.37 (1.12,13.60) mm2, P = 0.02] in unadjusted models, but this was attenuated and insignificant after adjusting for confounders.

Conclusions: While hepatic fat was low in children 4 to 8 years old, it was independently associated with estimated insulin resistance and exhibited sex-specific associations with glucose and triglycerides, suggesting hepatic fat may be an early indicator of metabolic dysfunction in youth.

Keywords: NAFLD; dyslipidemia; hepatic steatosis; insulin resistance; magnetic resonance imaging; pediatrics; prepubertal.

Publication types

  • Research Support, N.I.H., Extramural