Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women

Oliver Fiehn, W. Timothy Garvey, John W. Newman, Kerry H. Lok, Charles L. Hoppel, Sean H. Adams

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Insulin resistance progressing to type 2 diabetes mellitus (T2DM) is marked by a broad perturbation of macronutrient intermediary metabolism. Understanding the biochemical networks that underlie metabolic homeostasis and how they associate with insulin action will help unravel diabetes etiology and should foster discovery of new biomarkers of disease risk and severity. We examined differences in plasma concentrations of.350 metabolites in fasted obese T2DM vs. obese non-diabetic African-American women, and utilized principal components analysis to identify 158 metabolite components that strongly correlated with fasting HbA1c over a broad range of the latter (r =20.631; p,0.0001). In addition to many unidentified small molecules, specific metabolites that were increased significantly in T2DM subjects included certain amino acids and their derivatives (i.e., leucine, 2-ketoisocaproate, valine, cystine, histidine), 2-hydroxybutanoate, long-chain fatty acids, and carbohydrate derivatives. Leucine and valine concentrations rose with increasing HbA1c, and significantly correlated with plasma acetylcarnitine concentrations. It is hypothesized that this reflects a close link between abnormalities in glucose homeostasis, amino acid catabolism, and efficiency of fuel combustion in the tricarboxylic acid (TCA) cycle. It is speculated that a mechanism for potential TCA cycle inefficiency concurrent with insulin resistance is "anaplerotic stress" emanating from reduced amino acid-derived carbon flux to TCA cycle intermediates, which if coupled to perturbation in cataplerosis would lead to net reduction in TCA cycle capacity relative to fuel delivery.

Original languageEnglish (US)
Article numbere15234
Pages (from-to)1-10
Number of pages10
JournalPLoS One
Volume5
Issue number12
DOIs
StatePublished - 2010

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Metabolomics
Citric Acid Cycle
tricarboxylic acid cycle
metabolomics
African Americans
Medical problems
homeostasis
Homeostasis
Metabolites
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Plasmas
Glucose
glycohemoglobin
glucose
Valine
Insulin
metabolites
valine
Amino Acids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fiehn, O., Timothy Garvey, W., Newman, J. W., Lok, K. H., Hoppel, C. L., & Adams, S. H. (2010). Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. PLoS One, 5(12), 1-10. [e15234]. https://doi.org/10.1371/journal.pone.0015234

Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. / Fiehn, Oliver; Timothy Garvey, W.; Newman, John W.; Lok, Kerry H.; Hoppel, Charles L.; Adams, Sean H.

In: PLoS One, Vol. 5, No. 12, e15234, 2010, p. 1-10.

Research output: Contribution to journalArticle

Fiehn, O, Timothy Garvey, W, Newman, JW, Lok, KH, Hoppel, CL & Adams, SH 2010, 'Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women', PLoS One, vol. 5, no. 12, e15234, pp. 1-10. https://doi.org/10.1371/journal.pone.0015234
Fiehn, Oliver ; Timothy Garvey, W. ; Newman, John W. ; Lok, Kerry H. ; Hoppel, Charles L. ; Adams, Sean H. / Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. In: PLoS One. 2010 ; Vol. 5, No. 12. pp. 1-10.
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