Branched-chain amino acids and insulin metabolism

The Insulin Resistance Atherosclerosis Study (IRAS)

C. Christine Lee, Steve M. Watkins, Carlos Lorenzo, Lynne E. Wagenknecht, Dora Il'Yasova, Yii Der I Chen, Steven M. Haffner, Anthony J. Hanley

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort. RESEARCH DESIGN AND METHODS In 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics),wemeasured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests. RESULTS Elevated plasma BCAAs were inversely associated with SI andMCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (β = 20.0012 [95% CI20.0018,20.00059], P <0.001 for SI; β =20.0013 [95% CI 20.0018, 20.00082], P <0.001 for MCRI; and β = 0.0015 [95% CI 0.0008, 0.0023], P <0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95% CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR. CONCLUSIONS Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.

Original languageEnglish (US)
Pages (from-to)582-588
Number of pages7
JournalDiabetes Care
Volume39
Issue number4
DOIs
StatePublished - Apr 1 2016

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Branched Chain Amino Acids
Insulin Resistance
Atherosclerosis
Insulin
Hispanic Americans
African Americans
Fasting
Metabolomics
Isoleucine
Valine
Glucose Tolerance Test
Leucine
Mass Spectrometry
Odds Ratio

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Lee, C. C., Watkins, S. M., Lorenzo, C., Wagenknecht, L. E., Il'Yasova, D., Chen, Y. D. I., ... Hanley, A. J. (2016). Branched-chain amino acids and insulin metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care, 39(4), 582-588. https://doi.org/10.2337/dc15-2284

Branched-chain amino acids and insulin metabolism : The Insulin Resistance Atherosclerosis Study (IRAS). / Lee, C. Christine; Watkins, Steve M.; Lorenzo, Carlos; Wagenknecht, Lynne E.; Il'Yasova, Dora; Chen, Yii Der I; Haffner, Steven M.; Hanley, Anthony J.

In: Diabetes Care, Vol. 39, No. 4, 01.04.2016, p. 582-588.

Research output: Contribution to journalArticle

Lee, CC, Watkins, SM, Lorenzo, C, Wagenknecht, LE, Il'Yasova, D, Chen, YDI, Haffner, SM & Hanley, AJ 2016, 'Branched-chain amino acids and insulin metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)', Diabetes Care, vol. 39, no. 4, pp. 582-588. https://doi.org/10.2337/dc15-2284
Lee CC, Watkins SM, Lorenzo C, Wagenknecht LE, Il'Yasova D, Chen YDI et al. Branched-chain amino acids and insulin metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care. 2016 Apr 1;39(4):582-588. https://doi.org/10.2337/dc15-2284
Lee, C. Christine ; Watkins, Steve M. ; Lorenzo, Carlos ; Wagenknecht, Lynne E. ; Il'Yasova, Dora ; Chen, Yii Der I ; Haffner, Steven M. ; Hanley, Anthony J. / Branched-chain amino acids and insulin metabolism : The Insulin Resistance Atherosclerosis Study (IRAS). In: Diabetes Care. 2016 ; Vol. 39, No. 4. pp. 582-588.
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abstract = "OBJECTIVE Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort. RESEARCH DESIGN AND METHODS In 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics),wemeasured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests. RESULTS Elevated plasma BCAAs were inversely associated with SI andMCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (β = 20.0012 [95{\%} CI20.0018,20.00059], P <0.001 for SI; β =20.0013 [95{\%} CI 20.0018, 20.00082], P <0.001 for MCRI; and β = 0.0015 [95{\%} CI 0.0008, 0.0023], P <0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95{\%} CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR. CONCLUSIONS Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.",
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AU - Lorenzo, Carlos

AU - Wagenknecht, Lynne E.

AU - Il'Yasova, Dora

AU - Chen, Yii Der I

AU - Haffner, Steven M.

AU - Hanley, Anthony J.

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N2 - OBJECTIVE Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort. RESEARCH DESIGN AND METHODS In 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics),wemeasured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests. RESULTS Elevated plasma BCAAs were inversely associated with SI andMCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (β = 20.0012 [95% CI20.0018,20.00059], P <0.001 for SI; β =20.0013 [95% CI 20.0018, 20.00082], P <0.001 for MCRI; and β = 0.0015 [95% CI 0.0008, 0.0023], P <0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95% CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR. CONCLUSIONS Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.

AB - OBJECTIVE Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort. RESEARCH DESIGN AND METHODS In 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics),wemeasured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests. RESULTS Elevated plasma BCAAs were inversely associated with SI andMCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (β = 20.0012 [95% CI20.0018,20.00059], P <0.001 for SI; β =20.0013 [95% CI 20.0018, 20.00082], P <0.001 for MCRI; and β = 0.0015 [95% CI 0.0008, 0.0023], P <0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95% CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR. CONCLUSIONS Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.

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