AIMS/HYPOTHESIS: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. METHODS: We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of < or =1.06 or > or =1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. RESULTS: After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian- Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. CONCLUSIONS/ INTERPRETATION: These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass.
AIMS/HYPOTHESIS: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. METHODS: We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of < or =1.06 or > or =1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. RESULTS: After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian- Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. CONCLUSIONS/ INTERPRETATION: These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass.
Authors: Timothy R Koves; John R Ussher; Robert C Noland; Dorothy Slentz; Merrie Mosedale; Olga Ilkayeva; James Bain; Robert Stevens; Jason R B Dyck; Christopher B Newgard; Gary D Lopaschuk; Deborah M Muoio Journal: Cell Metab Date: 2008-01 Impact factor: 27.287
Authors: Stéphanie Chevalier; Errol B Marliss; José A Morais; Marie Lamarche; Réjeanne Gougeon Journal: Am J Clin Nutr Date: 2005-08 Impact factor: 7.045
Authors: Angela M Abbatecola; Luigi Ferrucci; Gianpaolo Ceda; Cosimo R Russo; Fulvio Lauretani; Stefania Bandinelli; Michelangela Barbieri; Giorgio Valenti; Giuseppe Paolisso Journal: J Gerontol A Biol Sci Med Sci Date: 2005-10 Impact factor: 6.053
Authors: Christine T Ferrara; Ping Wang; Elias Chaibub Neto; Robert D Stevens; James R Bain; Brett R Wenner; Olga R Ilkayeva; Mark P Keller; Daniel A Blasiole; Christina Kendziorski; Brian S Yandell; Christopher B Newgard; Alan D Attie Journal: PLoS Genet Date: 2008-03-14 Impact factor: 5.917
Authors: S H Shah; D R Crosslin; C S Haynes; S Nelson; C B Turer; R D Stevens; M J Muehlbauer; B R Wenner; J R Bain; B Laferrère; P Gorroochurn; J Teixeira; P J Brantley; V J Stevens; J F Hollis; L J Appel; L F Lien; B Batch; C B Newgard; L P Svetkey Journal: Diabetologia Date: 2011-11-08 Impact factor: 10.122
Authors: Mona Elbadawi-Sidhu; Rebecca A Baillie; Hongjie Zhu; Yii-Der Ida Chen; Mark O Goodarzi; Jerome I Rotter; Ronald M Krauss; Oliver Fiehn; Rima Kaddurah-Daouk Journal: Metabolomics Date: 2016-12-23 Impact factor: 4.290
Authors: Mahesh J Patel; Bryan C Batch; Laura P Svetkey; James R Bain; Christy Boling Turer; Carol Haynes; Michael J Muehlbauer; Robert D Stevens; Christopher B Newgard; Svati H Shah Journal: OMICS Date: 2013-10-11
Authors: Anna Coppola; Brett R Wenner; Olga Ilkayeva; Robert D Stevens; Mauro Maggioni; Theodore A Slotkin; Edward D Levin; Christopher B Newgard Journal: Am J Physiol Endocrinol Metab Date: 2012-12-18 Impact factor: 4.310