TY - JOUR
T1 - Branched-chain amino acid levels are inversely associated with incident and prevalent chronic kidney disease in people with type 2 diabetes
AU - de Klerk, Juliette A.
AU - Bijkerk, Roel
AU - Beulens, Joline W. J.
AU - van Zonneveld, Anton Jan
AU - Muilwijk, Mirte
AU - Harms, Peter P.
AU - Blom, Marieke T.
AU - 't Hart, Leendert M.
AU - Slieker, Roderick C.
N1 - Publisher Copyright: © 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - Aim: To investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal. Materials and Methods: The Hoorn Diabetes Care System cohort is a large prospective cohort consisting of individuals with type 2 diabetes from the northwest part of the Netherlands. In this cohort we assessed the association of baseline plasma levels of 172 metabolites with incident (Ntotal = 462/Ncase = 81) and prevalent (Ntotal = 1247/Ncase = 120) CKD using logistic regression. Additionally, replication in the UK Biobank, body mass index (BMI) mediation and causality of the association with Mendelian randomization was performed. Results: Elevated levels of total and individual branched-chain amino acids (BCAAs)—valine, leucine and isoleucine—were associated with an increased risk of incident CKD, but with reduced odds of prevalent CKD, where BMI was identified as an effect modifier. The observed inverse effects were replicated in the UK Biobank. Mendelian randomization analysis did not provide evidence for a causal relationship between BCAAs and prevalent CKD. Conclusions: Our study shows the intricate relationship between plasma BCAA levels and CKD in individuals with type 2 diabetes. While an association exists, its manifestation varies based on disease status and BMI, with no definitive evidence supporting a causal link between BCAAs and prevalent CKD.
AB - Aim: To investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal. Materials and Methods: The Hoorn Diabetes Care System cohort is a large prospective cohort consisting of individuals with type 2 diabetes from the northwest part of the Netherlands. In this cohort we assessed the association of baseline plasma levels of 172 metabolites with incident (Ntotal = 462/Ncase = 81) and prevalent (Ntotal = 1247/Ncase = 120) CKD using logistic regression. Additionally, replication in the UK Biobank, body mass index (BMI) mediation and causality of the association with Mendelian randomization was performed. Results: Elevated levels of total and individual branched-chain amino acids (BCAAs)—valine, leucine and isoleucine—were associated with an increased risk of incident CKD, but with reduced odds of prevalent CKD, where BMI was identified as an effect modifier. The observed inverse effects were replicated in the UK Biobank. Mendelian randomization analysis did not provide evidence for a causal relationship between BCAAs and prevalent CKD. Conclusions: Our study shows the intricate relationship between plasma BCAA levels and CKD in individuals with type 2 diabetes. While an association exists, its manifestation varies based on disease status and BMI, with no definitive evidence supporting a causal link between BCAAs and prevalent CKD.
KW - cohort study
KW - diabetic nephropathy
KW - observational study
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85184181476&partnerID=8YFLogxK
U2 - 10.1111/dom.15475
DO - 10.1111/dom.15475
M3 - Article
C2 - 38303102
SN - 1462-8902
VL - 26
SP - 1706
EP - 1713
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 5
ER -