BMI, RQ, Diabetes, and Sex Affect the Relationships Between Amino Acids and Clamp Measures of Insulin Action in Humans
- Anna E. Thalacker-Mercer1,2,3,4,
- Katherine H. Ingram2,5,
- Fangjian Guo2,
- Olga Ilkayeva6,
- Christopher B. Newgard6,7 and
- W. Timothy Garvey2,3⇑
- 1Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, AL
- 2Nutrition Sciences, University of Alabama, Birmingham, AL
- 3Birmingham Veterans Affairs Medical Center, Birmingham, AL
- 4Division of Nutritional Sciences, Cornell University, Ithaca, NY
- 5Department of Exercise Science and Sport Management, Kennesaw State University, Kennesaw, GA
- 6Department of Medicine, Duke University, Durham, NC
- 7Department of Pharmacology and Cancer Biology, Duke University, Durham, NC
- Corresponding author: W. Timothy Garvey, .
A.E.T.-M. and K.H.I. contributed equally to this work.
Previous studies have used indirect measures of insulin sensitivity to link circulating amino acids with insulin resistance and identify potential biomarkers of diabetes risk. Using direct measures (i.e., hyperinsulinemic-euglycemic clamps), we examined the relationships between the metabolomic amino acid profile and insulin action (i.e., glucose disposal rate [GDR]). Relationships between GDR and serum amino acids were determined among insulin-sensitive, insulin-resistant, and type 2 diabetic (T2DM) individuals. In all subjects, glycine (Gly) had the strongest correlation with GDR (positive association), followed by leucine/isoleucine (Leu/Ile) (negative association). These relationships were dramatically influenced by BMI, the resting respiratory quotient (RQ), T2DM, and sex. Gly had a strong positive correlation with GDR regardless of BMI, RQ, or sex but became nonsignificant in T2DM. In contrast, Leu/Ile was negatively associated with GDR in nonobese and T2DM subjects. Increased resting fat metabolism (i.e., low RQ) and obesity were observed to independently promote and negate the association between Leu/Ile and insulin resistance, respectively. Additionally, the relationship between Leu/Ile and GDR was magnified in T2DM males. Future studies are needed to determine whether Gly has a mechanistic role in glucose homeostasis and whether dietary Gly enrichment may be an effective intervention in diseases characterized by insulin resistance.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0396/-/DC1.
The opinions expressed are those of the authors and not necessarily those of the NIH or any other organization with which the authors are affiliated.
- Received March 11, 2013.
- Accepted October 4, 2013.
- © 2014 by the American Diabetes Association.
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