Objective: This study aimed to phenotype and compare adipose, hepatic, and muscle insulin sensitivity (IS) in a diet- and physical activity-controlled cohort of normoglycemic youth with obesity with that of participants without obesity (controls) to distinguish early metabolic abnormalities in pediatric obesity.
Methods: Thirty-eight participants (17 in the control group [BMI < 85th percentile] and 21 youth with obesity [BMI ≥ 95th percentile]; age: 12-21 years; 76% female; Tanner stage 4-5; sedentary) were enrolled. Tissue-specific IS was measured using a four-phase hyperinsulinemic-euglycemic clamp with glucose and glycerol isotope tracers to assess suppression of endogenous glucose release and lipolysis by insulin. Intramyocellular lipid content was assessed by 1 H-magnetic resonance spectroscopy, and hepatic fat fraction (HFF) and visceral fat were assessed by magnetic resonance imaging. Calf-muscle mitochondrial activity was measured with exercise-stimulated 31 P-magnetic resonance spectroscopy.
Results: Youth with obesity had higher HFF (P < 0.001), visceral fat (P = 0.024), and intramyocellular lipid content (P = 0.017) and lower muscle (glucose clearance rate [P < 0.001]), adipose (P < 0.0001), and hepatic IS (P < 0.003). Mitochondria postexercise response was not different. In participants with obesity, muscle IS inversely correlated with HFF (r = 0.700, P = 0.002) and suppressed free fatty acid concentrations (r = -0.65, P = 0.003).
Conclusions: Inactive normoglycemic youth with obesity had decreased muscle, adipose, and hepatic IS. Free fatty acids and liver fat were inversely associated with muscle IS, which argues for lipid-targeted interventions.
© 2019 The Obesity Society.