PMID- 38232082
OWN - NLM
STAT- MEDLINE
DCOM- 20240119
LR  - 20240201
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 19
IP  - 1
DP  - 2024
TI  - Causal associations between liver enzymes and diabetic microvascular 
      complications: A univariable and multivariable Mendelian randomization.
PG  - e0296894
LID - 10.1371/journal.pone.0296894 [doi]
LID - e0296894
AB  - BACKGROUND: Observational studies show that liver enzymes are diabetes risk 
      factors. However, previous observational investigations on the relationship 
      between liver enzymes and diabetic microvascular complications produced 
      contradictory results. The purpose of this research is to examine the independent 
      causal effects of liver enzymes on diabetic microvascular complications. METHODS: 
      Univariable Mendelian randomization (UVMR) and multivariable Mendelian 
      randomization (MVMR) were utilized to disentangle the causal effects. The 
      genome-wide association study (GWAS) summary-level statistics were collected from 
      the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) 
      were selected as genetic instruments with genome-wide significance (p < 5 x10-8). 
      Five UVMR approaches, including inverse variance weighted (IVW), Bayesian 
      weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier 
      (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including 
      the extended versions of IVW, MR-Egger, and the Q-minimization methods, were 
      performed to evaluate the causal effects. The robustness of the MR results was 
      further confirmed using several sensitivity analyses. RESULTS: UVMR revealed that 
      a genetically predisposed per standard deviation increase in serum alanine 
      aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in 
      type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 
      0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar 
      results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these 
      effects were consistent after controlling for glycemia and blood pressure using 
      MVMR analysis. Additionally, sensitivity analyses further strengthened the 
      causality. However, no significant associations were found between alkaline 
      phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular 
      complications. CONCLUSIONS: Robust evidence was demonstrated for an independent 
      causal effect of serum ALT or AST concentration on the risk of DR in T2DM. 
      Further investigations are necessary to elucidate the potential biological 
      mechanisms and confirm their clinical significance for early prevention and 
      intervention.
CI  - Copyright: (c) 2024 Li, Zhang. This is an open access article distributed under the 
      terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Li, Yang
AU  - Li Y
AUID- ORCID: 0009-0003-3428-454X
AD  - Department of Endocrinology, First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Zhang, Qiu
AU  - Zhang Q
AUID- ORCID: 0000-0002-0204-3528
AD  - Department of Endocrinology, First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
LA  - eng
PT  - Journal Article
DEP - 20240117
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/complications/genetics
MH  - Bayes Theorem
MH  - Genome-Wide Association Study
MH  - Mendelian Randomization Analysis
MH  - *Diabetic Retinopathy
MH  - Aspartate Aminotransferases
MH  - Liver
PMC - PMC10793938
COIS- The authors have declared that no competing interests exist.
EDAT- 2024/01/17 18:42
MHDA- 2024/01/19 06:42
PMCR- 2024/01/17
CRDT- 2024/01/17 13:33
PHST- 2023/04/26 00:00 [received]
PHST- 2023/12/18 00:00 [accepted]
PHST- 2024/01/19 06:42 [medline]
PHST- 2024/01/17 18:42 [pubmed]
PHST- 2024/01/17 13:33 [entrez]
PHST- 2024/01/17 00:00 [pmc-release]
AID - PONE-D-23-12191 [pii]
AID - 10.1371/journal.pone.0296894 [doi]
PST - epublish
SO  - PLoS One. 2024 Jan 17;19(1):e0296894. doi: 10.1371/journal.pone.0296894. 
      eCollection 2024.