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Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss.

Publication ,  Journal Article
Shah, SH; Crosslin, DR; Haynes, CS; Nelson, S; Turer, CB; Stevens, RD; Muehlbauer, MJ; Wenner, BR; Bain, JR; Laferrère, B; Gorroochurn, P ...
Published in: Diabetologia
February 2012

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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Published In

Diabetologia

DOI

EISSN

1432-0428

Publication Date

February 2012

Volume

55

Issue

2

Start / End Page

321 / 330

Location

Germany

Related Subject Headings

  • Weight Loss
  • Principal Component Analysis
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Insulin Resistance
  • Humans
  • Female
  • Endocrinology & Metabolism
  • Cohort Studies
 

Citation

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Chicago
ICMJE
MLA
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Shah, S. H., Crosslin, D. R., Haynes, C. S., Nelson, S., Turer, C. B., Stevens, R. D., … Svetkey, L. P. (2012). Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia, 55(2), 321–330. https://doi.org/10.1007/s00125-011-2356-5
Shah, S. H., D. R. Crosslin, C. S. Haynes, S. Nelson, C. B. Turer, R. D. Stevens, M. J. Muehlbauer, et al. “Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss.Diabetologia 55, no. 2 (February 2012): 321–30. https://doi.org/10.1007/s00125-011-2356-5.
Shah SH, Crosslin DR, Haynes CS, Nelson S, Turer CB, Stevens RD, et al. Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia. 2012 Feb;55(2):321–30.
Shah, S. H., et al. “Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss.Diabetologia, vol. 55, no. 2, Feb. 2012, pp. 321–30. Pubmed, doi:10.1007/s00125-011-2356-5.
Shah SH, Crosslin DR, Haynes CS, Nelson S, Turer CB, Stevens RD, Muehlbauer MJ, Wenner BR, Bain JR, Laferrère B, Gorroochurn P, Teixeira J, Brantley PJ, Stevens VJ, Hollis JF, Appel LJ, Lien LF, Batch B, Newgard CB, Svetkey LP. Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia. 2012 Feb;55(2):321–330.
Journal cover image

Published In

Diabetologia

DOI

EISSN

1432-0428

Publication Date

February 2012

Volume

55

Issue

2

Start / End Page

321 / 330

Location

Germany

Related Subject Headings

  • Weight Loss
  • Principal Component Analysis
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Insulin Resistance
  • Humans
  • Female
  • Endocrinology & Metabolism
  • Cohort Studies