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Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women.

Publication ,  Journal Article
Huffman, KM; Shah, SH; Stevens, RD; Bain, JR; Muehlbauer, M; Slentz, CA; Tanner, CJ; Kuchibhatla, M; Houmard, JA; Newgard, CB; Kraus, WE
Published in: Diabetes Care
September 2009

OBJECTIVE: To determine whether circulating metabolic intermediates are related to insulin resistance and beta-cell dysfunction in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: In 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry-based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates. RESULTS: The 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (S(I)) (R(2) = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R(2) = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R(2) = 0.39). Sex differences were found for metabolic predictors of S(I) and DI. CONCLUSIONS: In addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.

Duke Scholars

Published In

Diabetes Care

DOI

EISSN

1935-5548

Publication Date

September 2009

Volume

32

Issue

9

Start / End Page

1678 / 1683

Location

United States

Related Subject Headings

  • Young Adult
  • Tandem Mass Spectrometry
  • Principal Component Analysis
  • Overweight
  • Obesity
  • Middle Aged
  • Male
  • Insulin Resistance
  • Humans
  • Gas Chromatography-Mass Spectrometry
 

Citation

APA
Chicago
ICMJE
MLA
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Huffman, K. M., Shah, S. H., Stevens, R. D., Bain, J. R., Muehlbauer, M., Slentz, C. A., … Kraus, W. E. (2009). Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Diabetes Care, 32(9), 1678–1683. https://doi.org/10.2337/dc08-2075
Huffman, Kim M., Svati H. Shah, Robert D. Stevens, James R. Bain, Michael Muehlbauer, Cris A. Slentz, Charles J. Tanner, et al. “Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women.Diabetes Care 32, no. 9 (September 2009): 1678–83. https://doi.org/10.2337/dc08-2075.
Huffman KM, Shah SH, Stevens RD, Bain JR, Muehlbauer M, Slentz CA, et al. Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Diabetes Care. 2009 Sep;32(9):1678–83.
Huffman, Kim M., et al. “Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women.Diabetes Care, vol. 32, no. 9, Sept. 2009, pp. 1678–83. Pubmed, doi:10.2337/dc08-2075.
Huffman KM, Shah SH, Stevens RD, Bain JR, Muehlbauer M, Slentz CA, Tanner CJ, Kuchibhatla M, Houmard JA, Newgard CB, Kraus WE. Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Diabetes Care. 2009 Sep;32(9):1678–1683.

Published In

Diabetes Care

DOI

EISSN

1935-5548

Publication Date

September 2009

Volume

32

Issue

9

Start / End Page

1678 / 1683

Location

United States

Related Subject Headings

  • Young Adult
  • Tandem Mass Spectrometry
  • Principal Component Analysis
  • Overweight
  • Obesity
  • Middle Aged
  • Male
  • Insulin Resistance
  • Humans
  • Gas Chromatography-Mass Spectrometry