OBJECTIVE: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. RESEARCH DESIGN AND METHODS: Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio. RESULTS: Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R(2) = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R(2) = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males. CONCLUSIONS: BCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.
OBJECTIVE: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. RESEARCH DESIGN AND METHODS: Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio. RESULTS:Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R(2) = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R(2) = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males. CONCLUSIONS:BCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.
Authors: Svati H Shah; James R Bain; Michael J Muehlbauer; Robert D Stevens; David R Crosslin; Carol Haynes; Jennifer Dungan; L Kristin Newby; Elizabeth R Hauser; Geoffrey S Ginsburg; Christopher B Newgard; William E Kraus Journal: Circ Cardiovasc Genet Date: 2010-02-19
Authors: Kenneth C Copeland; Philip Zeitler; Mitchell Geffner; Cindy Guandalini; Janine Higgins; Kathryn Hirst; Francine R Kaufman; Barbara Linder; Santica Marcovina; Paul McGuigan; Laura Pyle; William Tamborlane; Steven Willi Journal: J Clin Endocrinol Metab Date: 2010-10-20 Impact factor: 5.958
Authors: Christopher B Newgard; Jie An; James R Bain; Michael J Muehlbauer; Robert D Stevens; Lillian F Lien; Andrea M Haqq; Svati H Shah; Michelle Arlotto; Cris A Slentz; James Rochon; Dianne Gallup; Olga Ilkayeva; Brett R Wenner; William S Yancy; Howard Eisenson; Gerald Musante; Richard S Surwit; David S Millington; Mark D Butler; Laura P Svetkey Journal: Cell Metab Date: 2009-04 Impact factor: 27.287
Authors: Kim M Huffman; Svati H Shah; Robert D Stevens; James R Bain; Michael Muehlbauer; Cris A Slentz; Charles J Tanner; Maragatha Kuchibhatla; Joseph A Houmard; Christopher B Newgard; William E Kraus Journal: Diabetes Care Date: 2009-06-05 Impact factor: 19.112
Authors: James R Bain; Robert D Stevens; Brett R Wenner; Olga Ilkayeva; Deborah M Muoio; Christopher B Newgard Journal: Diabetes Date: 2009-11 Impact factor: 9.461
Authors: Krystal A Irizarry; Diana R Mager; Lucila Triador; Michael J Muehlbauer; Andrea M Haqq; Michael Freemark Journal: Clin Endocrinol (Oxf) Date: 2019-01-31 Impact factor: 3.478
Authors: Krystal A Irizarry; James Bain; Merlin G Butler; Olga Ilkayeva; Michael Muehlbauer; Andrea M Haqq; Michael Freemark Journal: Clin Endocrinol (Oxf) Date: 2015-04-01 Impact factor: 3.478
Authors: G Á Martos-Moreno; A Mastrangelo; V Barrios; A García; J A Chowen; F J Rupérez; C Barbas; J Argente Journal: Int J Obes (Lond) Date: 2017-06-07 Impact factor: 5.095
Authors: Kevin R Short; Jennifer Q Chadwick; April M Teague; Mary A Tullier; Lisa Wolbert; Charlotte Coleman; Kenneth C Copeland Journal: J Clin Endocrinol Metab Date: 2019-08-01 Impact factor: 5.958
Authors: Samuel S Bailin; Cathy A Jenkins; Christopher Petucci; Jeffrey A Culver; Bryan E Shepherd; Joshua P Fessel; Todd Hulgan; John R Koethe Journal: AIDS Res Hum Retroviruses Date: 2018-05-02 Impact factor: 2.205
Authors: Shanshan Li; Yeyi Zhu; Edwina Yeung; Jorge E Chavarro; Changzheng Yuan; Alison E Field; Stacey A Missmer; James L Mills; Frank B Hu; Cuilin Zhang Journal: Int J Epidemiol Date: 2017-10-01 Impact factor: 7.196
Authors: Jennifer L LaBarre; Karen E Peterson; Maureen T Kachman; Wei Perng; Lu Tang; Wei Hao; Ling Zhou; Alla Karnovsky; Alejandra Cantoral; Martha María Téllez-Rojo; Peter X K Song; Charles F Burant Journal: J Clin Endocrinol Metab Date: 2020-07-01 Impact factor: 5.958