Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults

Würtz, Peter PHD
Soininen, Pasi PHD
Kangas, Antti J. MSC
Rönnemaa, Tapani MD; PHD
Lehtimäki, Terho MD; PHD
Kähönen, Mika MD; PHD
Viikari, Jorma S. MD; PHD
Raitakari, Olli T. MD; PHD
Ala-Korpela, Mika PHD

¹Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
²Computational Medicine, Institute of Clinical Medicine, University of Oulu, Oulu, Finland
³NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
⁴Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland
⁵Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland
⁶Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland
⁷Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
⁸Department of Clinical Physiology, Turku University Hospital, Turku, Finland

Corresponding author: Peter Würtz, [email protected].

Received May 9, 2012

Accepted August 9, 2012

Diabetes Care 36(3):p 648-655, March 2013. | DOI: 10.2337/dc12-0895

OBJECTIVE

Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin resistance index in healthy young adults.

RESEARCH DESIGN AND METHODS

Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin resistance was estimated by homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed using regression models adjusted for established risk factors. We further examined whether amino acid profiling could augment risk assessment of insulin resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.

RESULTS

Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up, while for women only leucine, valine, and phenylalanine predicted 6-year HOMA-IR (P < 0.05). None of the other amino acids were prospectively associated with HOMA-IR. The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men (odds ratio 2.09 [95% CI 1.38–3.17]; P = 0.0005); however, including the amino acid score in prediction models did not improve risk discrimination.

CONCLUSIONS

Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young, normoglycemic adults, with most pronounced associations for men. These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance.