Skip to main content

Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.

Publication ,  Journal Article
Gumus Balikcioglu, P; Jachthuber Trub, C; Balikcioglu, M; Ilkayeva, O; White, PJ; Muehlbauer, M; Bain, JR; Armstrong, S; Freemark, M
Published in: Endocrinology, diabetes & metabolism
January 2023

Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched-chain α-keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6-month lifestyle-intervention program.Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12-18 year) were analysed by flow-injection tandem MS and LC-MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA-IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables.Baseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI-metrics. Following lifestyle-intervention, α-keto-β-methylvalerate (α-KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA-IR at 6-month-follow-up. Glutamate/glutamine was positively associated with HOMA-IR at baseline and 6-month-follow-up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6-month-follow-up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight.BCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle-intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis.

Duke Scholars

Published In

Endocrinology, diabetes & metabolism

DOI

EISSN

2398-9238

ISSN

2398-9238

Publication Date

January 2023

Volume

6

Issue

1

Start / End Page

e388

Related Subject Headings

  • Uric Acid
  • Triglycerides
  • Tandem Mass Spectrometry
  • Pediatric Obesity
  • Male
  • Keto Acids
  • Insulin Resistance
  • Humans
  • Glutamine
  • Glutamates
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gumus Balikcioglu, P., Jachthuber Trub, C., Balikcioglu, M., Ilkayeva, O., White, P. J., Muehlbauer, M., … Freemark, M. (2023). Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity. Endocrinology, Diabetes & Metabolism, 6(1), e388. https://doi.org/10.1002/edm2.388
Gumus Balikcioglu, Pinar, Catherine Jachthuber Trub, Metin Balikcioglu, Olga Ilkayeva, Phillip J. White, Michael Muehlbauer, James R. Bain, Sarah Armstrong, and Michael Freemark. “Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.Endocrinology, Diabetes & Metabolism 6, no. 1 (January 2023): e388. https://doi.org/10.1002/edm2.388.
Gumus Balikcioglu P, Jachthuber Trub C, Balikcioglu M, Ilkayeva O, White PJ, Muehlbauer M, et al. Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity. Endocrinology, diabetes & metabolism. 2023 Jan;6(1):e388.
Gumus Balikcioglu, Pinar, et al. “Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.Endocrinology, Diabetes & Metabolism, vol. 6, no. 1, Jan. 2023, p. e388. Epmc, doi:10.1002/edm2.388.
Gumus Balikcioglu P, Jachthuber Trub C, Balikcioglu M, Ilkayeva O, White PJ, Muehlbauer M, Bain JR, Armstrong S, Freemark M. Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity. Endocrinology, diabetes & metabolism. 2023 Jan;6(1):e388.

Published In

Endocrinology, diabetes & metabolism

DOI

EISSN

2398-9238

ISSN

2398-9238

Publication Date

January 2023

Volume

6

Issue

1

Start / End Page

e388

Related Subject Headings

  • Uric Acid
  • Triglycerides
  • Tandem Mass Spectrometry
  • Pediatric Obesity
  • Male
  • Keto Acids
  • Insulin Resistance
  • Humans
  • Glutamine
  • Glutamates