Nonalcoholic fatty liver disease in obese adolescent females is associated with multi-tissue insulin resistance and visceral adiposity markers

Melanie Cree-Green; Sonalee Ravi; Anne-Marie Carreau; Rachel Sewell; Amy Baumgartner; Gregory Coe; Bryan C Bergman; Ann Scherzinger; Thomas Jensen; Laura Pyle; Kristen J Nadeau

doi:10.1016/j.metop.2019.100011

Nonalcoholic fatty liver disease in obese adolescent females is associated with multi-tissue insulin resistance and visceral adiposity markers

Metabol Open. 2019 Jun 8:2:100011. doi: 10.1016/j.metop.2019.100011. eCollection 2019 Jun.

Authors

Melanie Cree-Green^{1

2}, Sonalee Ravi^{1

3}, Anne-Marie Carreau¹, Rachel Sewell¹, Amy Baumgartner¹, Gregory Coe¹, Bryan C Bergman⁴, Ann Scherzinger⁵, Thomas Jensen⁴, Laura Pyle⁶, Kristen J Nadeau^{1

2

3}

Affiliations

¹ Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
² Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract

Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and visceral adiposity in adults and boys, but girls with NAFLD are understudied. We sought to evaluate adipose, liver, and skeletal muscle insulin sensitivity in obese adolescent females with or without hepatic steatosis (HS) (intrahepatic triglyceride (IHTG) content >5.5%) along with cardiometabolic components typically associated with IR.

Study design: 73 obese adolescent girls at high risk for NAFLD were enrolled. Participants underwent fasting labs, an MRI to measure IHTG and visceral fat, ³¹phosphorous MR spectroscopy for muscle mitochondrial function, ¹H MR spectroscopy for intramyocellular lipid (IMCL), bicycle ergometry to assess VO₂peak and a 4-phase hyperinsulinemic euglycemic clamp with isotope tracers to measure hepatic and peripheral IR. 29 participants had HS [age 15 yrs(13,16), BMI%ile 98.7(97.4,99.0), IHTG 10.4%(8.0,13.5)] and 44 did not [age 15 yrs(13,17), BMI%ile 98.5(96.2,99.0), IHTG 2.0%(1.1,3.0)].

Results: During hyperinsulinemia, participants with HS vs. non-HS had failure to suppress free fatty acids (p = 0.008), endogenous glucose release (p = 0.002), and a lower glucose metabolic rate of disappearance (Rd) (p = 0.012). Girls with NALFD also had higher visceral fat (p < 0.001), systolic blood pressure (p = 0.026), triglycerides (p = 0.02), ALT (p < 0.01) and white blood cell count (p < 0.01), and lower adiponectin (p = 0.02). There was no difference between girls with and without HS in systemic glycerol turnover measured with glycerol release, or in IMCL, mitochondrial function or VO₂peak.

Conclusions: Obese adolescent girls with HS have evidence of multi-tissue IR, visceral adiposity, inflammation and multiple components of the metabolic syndrome, arguing for close cardiometabolic surveillance over time of girls with HS.

Keywords: Adolescent; Girls; Insulin resistance; NAFLD.