Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults
Peter Würtz,Pasi Soininen,Pasi Soininen,Antti J. Kangas,Tapani Rönnemaa,Terho Lehtimäki,Mika Kähönen,Jorma Viikari,Olli T. Raitakari,Olli T. Raitakari,Mika Ala-Korpela,Mika Ala-Korpela +11 more
Reads0
Chats0
TLDR
The association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance, with most pronounced associations for men.Abstract:
OBJECTIVE Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin resistance index in healthy young adults.
RESEARCH DESIGN AND METHODS Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin resistance was estimated by homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed using regression models adjusted for established risk factors. We further examined whether amino acid profiling could augment risk assessment of insulin resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.
RESULTS Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up, while for women only leucine, valine, and phenylalanine predicted 6-year HOMA-IR ( P < 0.05). None of the other amino acids were prospectively associated with HOMA-IR. The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men (odds ratio 2.09 [95% CI 1.38–3.17]; P = 0.0005); however, including the amino acid score in prediction models did not improve risk discrimination.
CONCLUSIONS Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young, normoglycemic adults, with most pronounced associations for men. These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance.read more
Citations
More filters
Journal ArticleDOI
Mechanisms of Insulin Action and Insulin Resistance
TL;DR: This work aims to develop an integrated physiological perspective, placing the intricate signaling effectors that carry out the cell-autonomous response to insulin in the context of the tissue-specific functions that generate the coordinated organismal response.
Journal ArticleDOI
Emerging applications of metabolomics in drug discovery and precision medicine
TL;DR: This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases, the growing role of metabolites in drug discovery and its potential effect on precision medicine.
Journal ArticleDOI
Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis
Marta Guasch-Ferré,Adela Hruby,Estefanía Toledo,Clary B. Clish,Miguel Ángel Martínez-González,Miguel Ángel Martínez-González,Jordi Salas-Salvadó,Frank B. Hu,Frank B. Hu +8 more
TL;DR: In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
Journal ArticleDOI
Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Cardiovascular Epidemiology and Genetics
TL;DR: An automated high-throughput serum NMR metabolomics platform that provides quantitative molecular data on 14 lipoprotein subclasses, their lipid concentrations and composition, apolipoprotein A-I and B, multiple cholesterol and triglyceride measures, albumin, various fatty acids as well as on numerous low-molecular-weight metabolites, including amino acids, glycolysis related measures and ketone bodies is developed.
Journal ArticleDOI
Metabolomics and Metabolic Diseases: Where Do We Stand?
TL;DR: Progress in metabolomics and challenges for the future are reviewed here.
References
More filters
Journal ArticleDOI
Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity
K. G. M. M. Alberti,Robert H. Eckel,Scott M. Grundy,Paul Zimmet,James I. Cleeman,Karen A. Donato,Jean Charles Fruchart,W. Philip T. James,Catherine M. Loria,Sidney C. Smith +9 more
TL;DR: It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool, and a single set of cut points would be used for all components except waist circumference, for which further work is required.
Journal ArticleDOI
Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond
TL;DR: Two new measures, one based on integrated sensitivity and specificity and the other on reclassification tables, are introduced that offer incremental information over the AUC and are proposed to be considered in addition to the A UC when assessing the performance of newer biomarkers.
Journal ArticleDOI
Use and Abuse of HOMA Modeling
TL;DR: The HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data, however, as with all models, the primary input data needs to be robust, and the data need to be interpreted carefully.
Journal ArticleDOI
A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance
Christopher B. Newgard,Jie An,James R. Bain,Michael J. Muehlbauer,Robert 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 +20 more
TL;DR: Findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.
Journal ArticleDOI
Metabolite profiles and the risk of developing diabetes
Thomas J. Wang,Martin G. Larson,Martin G. Larson,Ramachandran S. Vasan,Ramachandran S. Vasan,Susan Cheng,Susan Cheng,Susan Cheng,Eugene P. Rhee,Eugene P. Rhee,Elizabeth L. McCabe,Elizabeth L. McCabe,Gregory D. Lewis,Gregory D. Lewis,Caroline S. Fox,Caroline S. Fox,Paul F. Jacques,Céline Fernandez,Christopher J. O'Donnell,Christopher J. O'Donnell,Christopher J. O'Donnell,Stephen A Carr,Vamsi K. Mootha,Vamsi K. Mootha,Jose C. Florez,Jose C. Florez,Amanda Souza,Olle Melander,Clary B. Clish,Robert E. Gerszten,Robert E. Gerszten +30 more
TL;DR: Findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment.
Related Papers (5)
Metabolite profiles and the risk of developing diabetes
Thomas J. Wang,Martin G. Larson,Martin G. Larson,Ramachandran S. Vasan,Ramachandran S. Vasan,Susan Cheng,Susan Cheng,Susan Cheng,Eugene P. Rhee,Eugene P. Rhee,Elizabeth L. McCabe,Elizabeth L. McCabe,Gregory D. Lewis,Gregory D. Lewis,Caroline S. Fox,Caroline S. Fox,Paul F. Jacques,Céline Fernandez,Christopher J. O'Donnell,Christopher J. O'Donnell,Christopher J. O'Donnell,Stephen A Carr,Vamsi K. Mootha,Vamsi K. Mootha,Jose C. Florez,Jose C. Florez,Amanda Souza,Olle Melander,Clary B. Clish,Robert E. Gerszten,Robert E. Gerszten +30 more
A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance
Christopher B. Newgard,Jie An,James R. Bain,Michael J. Muehlbauer,Robert 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 +20 more