Melanie Cree-Green1,2, Pattara Wiromrat1, Jacob J Stuppy1,3, Jessica Thurston4, Bryan C Bergman5, Amy D Baumgartner1, Samantha Bacon5, Ann Scherzinger6, Laura Pyle4,7, Kristen J Nadeau1,2. 1. Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 2. Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 3. Department of Biomedical Sciences and Biotechnology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 4. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 5. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 6. Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 7. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Abstract
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.
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.
Authors: Elizabeth J Mayer-Davis; Jean M Lawrence; Dana Dabelea; Jasmin Divers; Scott Isom; Lawrence Dolan; Giuseppina Imperatore; Barbara Linder; Santica Marcovina; David J Pettitt; Catherine Pihoker; Sharon Saydah; Lynne Wagenknecht Journal: N Engl J Med Date: 2017-04-13 Impact factor: 91.245
Authors: Melanie Cree-Green; Ninghe Cai; Laura Pyle; Brandy Ringham; Mark S Brown; Bradley R Newcomer; Kristen J Nadeau; Dana Dabelea Journal: J Clin Endocrinol Metab Date: 2017-05-01 Impact factor: 5.958
Authors: Bryan C Bergman; Leigh Perreault; Allison Strauss; Samantha Bacon; Anna Kerege; Kathleen Harrison; Joseph T Brozinick; Devon M Hunerdosse; Mary C Playdon; William Holmes; Hai Hoang Bui; Phil Sanders; Parker Siddall; Tao Wei; Melissa K Thomas; Ming Shang Kuo; Robert H Eckel Journal: Am J Physiol Endocrinol Metab Date: 2017-10-03 Impact factor: 4.310
Authors: Bolormaa Vandanmagsar; Yun-Hee Youm; Anthony Ravussin; Jose E Galgani; Krisztian Stadler; Randall L Mynatt; Eric Ravussin; Jacqueline M Stephens; Vishwa Deep Dixit Journal: Nat Med Date: 2011-01-09 Impact factor: 53.440
Authors: Melanie Cree-Green; Haseeb Rahat; Bradley R Newcomer; Bryan C Bergman; Mark S Brown; Gregory V Coe; Lindsey Newnes; Yesenia Garcia-Reyes; Samantha Bacon; Jessica E Thurston; Laura Pyle; Ann Scherzinger; Kristen J Nadeau Journal: J Endocr Soc Date: 2017-06-01