| Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. | |
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MedLine Citation:
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PMID: 22065088 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. METHODS: Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, β-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6 month plasma samples from 500 participants who had lost ≥4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (∆HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n = 22). RESULTS: Mean weight loss was 8.67 ± 4.28 kg; mean ∆HOMA-IR was -0.80 ± 1.73, range -28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r = 0.50, p < 0.0001) and independently associated with ∆HOMA-IR (p < 0.0001). ∆HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ∆HOMA-IR (r = 0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ∆HOMA-IR (p = 0.007). CONCLUSIONS/INTERPRETATION: A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity. |
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Authors:
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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 |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-8 |
Journal Detail:
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Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Medicine, DUMC, Duke University Medical Center, Box 3445, Durham, NC, 27710, USA, svati.shah@duke.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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