Branched chain amino acids are associated with metabolic complications in liver transplant recipients

Marco Böhler; Eline H van den Berg; Maria C T Almanza; Margery A Connelly; Stephan J L Bakker; Vincent E de Meijer; Robin P F Dullaart; Hans Blokzijl; TransplantLines Investigators

doi:10.1016/j.clinbiochem.2022.01.009

Branched chain amino acids are associated with metabolic complications in liver transplant recipients

Clin Biochem. 2022 Apr:102:26-33. doi: 10.1016/j.clinbiochem.2022.01.009. Epub 2022 Feb 7.

Authors

Marco Böhler¹, Eline H van den Berg², Maria C T Almanza³, Margery A Connelly⁴, Stephan J L Bakker⁵, Vincent E de Meijer⁶, Robin P F Dullaart⁷, Hans Blokzijl²; TransplantLines Investigators

Collaborators

TransplantLines Investigators:
E Hak⁸, B G Hepkema⁹, F Klont¹⁰, T J Knobbe¹¹, D Kremer¹¹, H G D Leuvenink¹², W S Lexmond¹³, H G M Niesters¹⁴, L J van Pelt⁹, R A Pol¹², R J Porte¹⁵, A V Ranchor¹⁶, J S F Sanders¹¹, M J Siebelink¹⁷, R J H J A Slart¹⁸, J C Swarte¹¹, D J Touw¹⁹, M C van den Heuvel²⁰, C van Leer-Buter¹⁴, M van Londen¹¹, E A M Verschuuren²¹, M J Vos²², R K Weersma²³

Affiliations

¹ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: m.t.bohler@umcg.nl.
² Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: h.blokzijl@umcg.nl.
³ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: e.h.wouters@umcg.nl.
⁴ Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, United States. Electronic address: connem5@labcorp.com.
⁵ Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: s.j.l.bakker@umcg.n.
⁶ Department of Surgery, Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: v.e.de.meijer@umcg.nl.
⁷ Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: dull.fam@12move.nl.
⁸ Groningen Research Institute of Pharmacy, Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTE2), University of Groningen, Groningen, The Netherlands.
⁹ Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁰ Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Geneva, Switzerland.
¹¹ Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹² Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹³ Department of Pediatrics, Division of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁴ Department of Medical Microbiology and Infection Prevention, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁵ Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
¹⁶ Department of Health Psychology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁷ University Medical Center Groningen Transplant Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁸ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁹ Department of Clinical Pharmacy and Pharmacology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.
²⁰ Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
²¹ Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²² Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²³ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

PMID: 35143831
DOI: 10.1016/j.clinbiochem.2022.01.009

Abstract

Background: Obesity, dyslipidemia and type 2 diabetes (T2D) contribute substantially to increased cardiovascular morbidity and mortality in patients after orthotopic liver transplantation (OLTx). Elevated plasma branched chain amino acids (BCAA) are linked to metabolic disturbances and cardiovascular disease (CVD) risk profiles in several non-OLTx populations.

Methods: Cross-sectional analysis of liver transplant recipients from TransplantLines, a single-center biobank and cohort study. BCAA plasma levels were measured by means of nuclear-magnetic resonance spectroscopy. CVD and cardiometabolic factors were collected by using data from electronic patient records. Associations were determined between BCAA plasma levels and T2D, Metabolic Syndrome (MetS), CVD as well as mTOR inhibition in liver transplant recipients.

Results: 336 Patients were divided into sex-stratified tertiles of total BCAA. MetS (P < 0.001) and T2D (P = 0.002) were significantly more frequent in subjects in the highest BCAA tertile. In logistic regression analyses, the multivariable adjusted odds ratio (OR) per 1 standard deviation increase in BCAA was 1.68 (95%CI: 1.18-2.20, P = 0.003) for MetS and 1.60 (95%CI: 1.14-2.23, P = 0.006) for T2D. Use of Sirolimus (mTOR inhibitor) was significantly associated with higher BCAA plasma levels, independent of age, sex, time after OLTx, MetS and other immunosuppressive medication (adjusted P = 0.002).

Conclusion: Elevated BCAA plasma levels are associated with T2D, MetS and use of Sirolimus in liver transplant recipients. BCAA plasma levels may represent a valuable biomarker for cardiometabolic complications after OLTx.

Keywords: Branched chain amino acids; Dyslipidemia; Liver transplantation; Metabolic syndrome; Sirolimus; Type 2 diabetes.

MeSH terms

Amino Acids, Branched-Chain* / adverse effects
Cohort Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 2* / complications
Humans
Liver Transplantation*
Risk Factors

Substances

Amino Acids, Branched-Chain