PMID- 38174155
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240105
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 8
IP  - 1
DP  - 2023 Dec 1
TI  - Exploration of Metabolomic Markers Associated With Declining Kidney Function in 
      People With Type 2 Diabetes Mellitus.
PG  - bvad166
LID - 10.1210/jendso/bvad166 [doi]
LID - bvad166
AB  - BACKGROUND: Metabolomics, the study of small molecules in biological systems, can 
      provide valuable insights into kidney dysfunction in people with type 2 diabetes 
      mellitus (T2DM), but prospective studies are scarce. We investigated the 
      association between metabolites and kidney function decline in people with T2DM. 
      METHODS: The Edinburgh Type 2 Diabetes Study, a population-based cohort of 1066 
      men and women aged 60 to 75 years with T2DM. We measured 149 serum metabolites at 
      baseline and investigated individual associations with baseline estimated 
      glomerular filtration rate (eGFR), incident chronic kidney disease [CKD; eGFR 
      <60 mL/min/(1.73 m)(2)], and decliner status (5% eGFR decline per year). RESULTS: 
      At baseline, mean eGFR was 77.5 mL/min/(1.73 m)(2) (n = 1058), and 216 
      individuals had evidence of CKD. Of those without CKD, 155 developed CKD over a 
      median 7-year follow-up. Eighty-eight metabolites were significantly associated 
      with baseline eGFR (beta range -4.08 to 3.92; P(FDR) < 0.001). Very low density 
      lipoproteins, triglycerides, amino acids (AAs), glycoprotein acetyls, and fatty 
      acids showed inverse associations, while cholesterol and phospholipids in 
      high-density lipoproteins exhibited positive associations. AA isoleucine, 
      apolipoprotein A1, and total cholines were not only associated with baseline 
      kidney measures (P(FDR) < 0.05) but also showed stable, nominally significant 
      association with incident CKD and decline. CONCLUSION: Our study revealed 
      widespread changes within the metabolomic profile of CKD, particularly in 
      lipoproteins and their lipid compounds. We identified a smaller number of 
      individual metabolites that are specifically associated with kidney function 
      decline. Replication studies are needed to confirm the longitudinal findings and 
      explore if metabolic signals at baseline can predict kidney decline.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Krasauskaite, Justina
AU  - Krasauskaite J
AUID- ORCID: 0000-0002-9583-3480
AD  - Usher Institute, University of Edinburgh, EH8 9AG, Edinburgh, UK.
FAU - Conway, Bryan
AU  - Conway B
AD  - Centre for Cardiovascular Science, The Queen's Medical Research Institute, 
      Edinburgh BioQuarter, University of Edinburgh, EH16 4TJ, Edinburgh, UK.
FAU - Weir, Christopher
AU  - Weir C
AUID- ORCID: 0000-0002-6494-4903
AD  - Usher Institute, University of Edinburgh, EH8 9AG, Edinburgh, UK.
FAU - Huang, Zhe
AU  - Huang Z
AUID- ORCID: 0000-0002-4441-0015
AD  - Usher Institute, University of Edinburgh, EH8 9AG, Edinburgh, UK.
FAU - Price, Jackie
AU  - Price J
AUID- ORCID: 0000-0003-3251-3970
AD  - Usher Institute, University of Edinburgh, EH8 9AG, Edinburgh, UK.
LA  - eng
PT  - Journal Article
DEP - 20231222
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC10763986
OTO - NOTNLM
OT  - chronic kidney disease
OT  - metabolomics
OT  - type 2 diabetes
EDAT- 2024/01/04 11:43
MHDA- 2024/01/04 11:44
PMCR- 2023/12/22
CRDT- 2024/01/04 04:19
PHST- 2023/09/10 00:00 [received]
PHST- 2024/01/04 11:44 [medline]
PHST- 2024/01/04 11:43 [pubmed]
PHST- 2024/01/04 04:19 [entrez]
PHST- 2023/12/22 00:00 [pmc-release]
AID - bvad166 [pii]
AID - 10.1210/jendso/bvad166 [doi]
PST - epublish
SO  - J Endocr Soc. 2023 Dec 22;8(1):bvad166. doi: 10.1210/jendso/bvad166. eCollection 
      2023 Dec 1.