U.S. flagAn official website of the United States government
                    Here's how you know **Official websites use .gov**
                            
                            A **.gov** website belongs to an official government organization in the United States.
 **Secure .gov websites use HTTPS**
                            
                            A **lock** (                            
                              A locked padlock                                                      
                            
                            ) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Menu Agricultural Research Service
						
                    U.S. DEPARTMENT OF AGRICULTURE
 Obesity and Metabolism Research: Davis, CA
 close



    Research

                    Research Projects
                                    Publications
                                    Collaborations
                                    News
                People

                    Staff Listing
                                    Careers


        


                    Laboratories
                        Bennett Group
                                    Huang Group
                                    Keim Group
                                    Laugero Group
                                    Newman GroupSearch small
                    Search
            
            ARS Home
                                About ARS
                                Contact Us




ARS Home Pacific West Area Davis, California Western Human Nutrition Research Center Obesity and Metabolism Research Research Publications at this Location





- ARS National Programs
- Search for a scientific manuscript
- Search for a research project
- ARS Software
- Programs and Projects
- Collaborations
- Subjects of Investigation
- Publications

Title:   Author  item
                                            FIEHN, OLIVER - University Of Californiaitem
                                            GARVEY, W. TIMOTHY - University Of Alabamaitem
                                            Newman, Johnitem
                                            LOK, KERRY - University Of Alabamaitem
                                            HOPPEL, CHARLES - Case Western Reserve University (CWRU)item
                                            Adams, Sean
  Submitted to: PLOS ONE
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 10/31/2010
                                    Publication  Date: 12/10/2010
                                    Citation: Fiehn, O., 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. Vol.5(12): e15234.Interpretive Summary: 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 levels of >350 metabolites in fasted obese T2DM vs. obese non-diabetic    African-American women, and utilized principal components analysis (PCA) to identify 53 metabolite components, many unique, contributing to a PC score strongly correlated with fasting HbA1c over a broad range of the latter (r=0.74; p<0.0001).  In addition to many unidentified metabolites, specific metabolites that were increased significantly in T2DM subjects included certain amino acids (i.e., leucine/2-ketoisocaproate, valine, cystine, histidine), 2-hydroxybutanoate (2-HB), long-chain fatty acids, and carbohydrate derivatives.  Leucine and valine concentrations significantly correlated with total acylcarnitine levels across the study cohort (and rising with increasing HbA1c).  This appears to reflect a close link between abnormalities in glucose homeostasis, amino acid catabolism, and inefficiency of fuel combustion in the tricarboxylic acid (TCA) cycle.  One proposed mechanism for the latter is “anaplerotic stress” concomitant with reduced amino acid-derived carbon flux to TCA cycle intermediates coupled to perturbation in cataplerosis (TCA intermediate loss).
                                Technical 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 levels of >350 metabolites in fasted obese T2DM vs. obese non-diabetic    African-American women, and utilized principal components analysis (PCA) to identify 53 metabolite components, many unique, contributing to a PC score strongly correlated with fasting HbA1c over a broad range of the latter (r=0.74; p<0.0001).  In addition to many unidentified metabolites, specific metabolites that were increased significantly in T2DM subjects included certain amino acids (i.e., leucine/2-ketoisocaproate, valine, cystine, histidine), 2-hydroxybutanoate (2-HB), long-chain fatty acids, and carbohydrate derivatives.  Leucine and valine concentrations significantly correlated with total acylcarnitine levels across the study cohort (and rising with increasing HbA1c).  This appears to reflect a close link between abnormalities in glucose homeostasis, amino acid catabolism, and inefficiency of fuel combustion in the tricarboxylic acid (TCA) cycle.  One proposed mechanism for the latter is “anaplerotic stress” concomitant with reduced amino acid-derived carbon flux to TCA cycle intermediates coupled to perturbation in cataplerosis (TCA intermediate loss).


Return to top


Connect with ARS Sign up


ARS Home
                            USDA.gov
                            Plain Writing
                            Policies & Links
                            Civil Rights Statements
                            FOIA
                            Accessibility Statement
                            Privacy Policy
                            Non-Discrimination Statement
                            Quality of Information
                            USA.gov
                            WhiteHouse.gov