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. 2009 Sep;32(9):1678-83.
doi: 10.2337/dc08-2075. Epub 2009 Jun 5.

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

Kim M Huffman  1 , Svati H Shah, Robert D Stevens, James R Bain, Michael Muehlbauer, Cris A Slentz, Charles J Tanner, Maragatha Kuchibhatla, Joseph A Houmard, Christopher B Newgard, William E Kraus
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Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women

Kim M Huffman et al. Diabetes Care. 2009 Sep.

Abstract

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.

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Figures

Figure 1
Figure 1
Relationships between factor scores and measures of insulin action. A: Relationship between factor 4 score and SI. B: Relationship between factor 2 score and AIRg. C: Relationship between factor 4 score and DI. D: Relationship between factor 2 score and DI.
See this image and copyright information in PMC

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References

    1. Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. 1922. Can Med Assoc J 1991; 145: 1281– 1286 - PMC - PubMed
    1. Muoio DM, Newgard CB. Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 193– 205 - PubMed
    1. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol 2004; 96: 101– 106 - PubMed
    1. Ha AM, Lien LF, Boan J, Arlotto M, Slentz CA, Muehlbauer MJ, Rochon J, Gallup D, McMahon RL, Bain JR, Stevens R, Millington D, Butler MD, Newgard CB, Svetkey LP. The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: rationale and design. Contemp Clin Trials 2005; 26: 616– 625 - PubMed
    1. Lien LF, Ha AM, Arlotto M, Slentz CA, Muehlbauer MJ, McMahon RL, Rochon J, Gallup D, Bain JR, Ilkayeva O, Wenner BR, Stevens RD, Millington DS, Muoio DM, Butler MD, Newgard CB, Svetkey LP. The STEDMAN project: biophysical, biochemical and metabolic effects of a behavioral weight loss intervention during weight loss, maintenance, and regain. Omics 2009; 13: 21– 35 - PMC - PubMed

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