Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
Journal article, 2018

Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.

Insulin secretion

Insulin resistance

3-Hydroxyisobutyric acid (3-HIB)

Branched-chain amino acids (BCAAs)



Adil Mardinoglu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Royal Institute of Technology (KTH)

Silvia Gogg

University of Gothenburg

Luca A. Lotta

University of Cambridge

Annika Nerstedt

University of Gothenburg

Jan Boren

University of Gothenburg

Matthias Blueher

Leipzig University

Ele Ferrannini

CNR Inst Clin Physiol

Claudia Langenberg

University of Cambridge

Nicholas J. Wareham

University of Cambridge

Markku Laakso

University of Eastern Finland

Ulf Smith

University of Gothenburg


2352-3964 (eISSN)

Vol. 27 151-155

Subject Categories

Endocrinology and Diabetes

Other Clinical Medicine

Cell and Molecular Biology





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