PMID- 36157454
OWN - NLM
STAT- MEDLINE
DCOM- 20220928
LR  - 20220928
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 13
DP  - 2022
TI  - Metabolomic comparison followed by cross-validation of enzyme-linked 
      immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in 
      Chinese with type 2 diabetes.
PG  - 986303
LID - 10.3389/fendo.2022.986303 [doi]
LID - 986303
AB  - PURPOSE: To identify the biomarkers in the critical period of development in 
      diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and 
      untargeted metabolomics, and to explore the feasibility of their clinical 
      application. METHODS: This case-control study described the differential 
      metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with 
      disease duration >/= 10 years and 27 controls matched cases. Targeted metabolomics 
      using high-resolution mass spectrometry with liquid chromatography was performed 
      on plasma samples of subjects. The results were compared to our previous 
      untargeted metabolomics study and ELISA was performed to validate the mutual 
      differential metabolites of targeted and untargeted metabolomics on plasma. 
      Multiple linear regression analyses were performed to adjust for the significance 
      of different metabolites between groups. RESULT: Mean age of the subjects was 
      66.3 years and mean T2DM duration was 16.5 years. By cross-validating with 
      results from previous untargeted metabolomic assays, we found that L-Citrulline 
      (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines 
      (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid 
      (EPA) were the most distinctive metabolites biomarkers to distinguish the 
      severity of DR for two different metabolomic approaches in our study. We mainly 
      found that samples in the DR stage showed lower serum level of Cit and higher 
      serum level of IAA compared with samples in the T2DM stage, while during the 
      progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR 
      stage were significantly lower than NPDR stage. Among them, 4 differential key 
      metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA. 
      CONCLUSION: This is the first study to compare the results of targeted and 
      untargeted metabolomics via liquid chromatography-mass spectrometry to find the 
      serum biomarkers which could reflect the metabolic variations among different 
      stages of DR in Chinese. The progression of DR in Chinese at different critical 
      stages was related to the serum levels of specific differential metabolites, of 
      which there is a significant correlation between DR progression and increased IAA 
      and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are 
      needed to confirm our results. Based on this study, it could be inferred that the 
      accuracy of targeted metabolomics for metabolite expression in serum is to some 
      extent higher than that of untargeted metabolomics.
CI  - Copyright (c) 2022 Wang, Tang, Jin, Ren, Li, Zhang, Zhong, Cao, Wang, Zhou, Zhao, 
      Huang and Qu.
FAU - Wang, Zongyi
AU  - Wang Z
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Tang, Jiyang
AU  - Tang J
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Jin, Enzhong
AU  - Jin E
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Ren, Chi
AU  - Ren C
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Li, Siying
AU  - Li S
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Zhang, Linqi
AU  - Zhang L
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Zhong, Yusheng
AU  - Zhong Y
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Cao, Yu
AU  - Cao Y
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Wang, Jianmin
AU  - Wang J
AD  - Department of Ophthalmology, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, China.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Department of Ophthalmology, Tianjin Medical University General Hospital, 
      Tianjin, China.
FAU - Zhao, Mingwei
AU  - Zhao M
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Huang, Lvzhen
AU  - Huang L
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
FAU - Qu, Jinfeng
AU  - Qu J
AD  - Department of Ophthalmology, Peking University People's Hospital, Eye Diseases 
      and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of 
      Retinal and Choroid Diseases, College of Optometry, Peking University Health 
      Science Center, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220908
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Biomarkers)
RN  - 0 (Phosphatidylcholines)
RN  - 0GEI24LG0J (Chenodeoxycholic Acid)
RN  - 14919-34-7 (hexanoylcarnitine)
RN  - 29VT07BGDA (Citrulline)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Aged
MH  - Biomarkers
MH  - Carnitine/analogs & derivatives
MH  - Case-Control Studies
MH  - Chenodeoxycholic Acid
MH  - China/epidemiology
MH  - Citrulline
MH  - *Diabetes Mellitus, Type 2/complications
MH  - *Diabetic Retinopathy/diagnosis/etiology
MH  - Eicosapentaenoic Acid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Metabolomics
MH  - Phosphatidylcholines
PMC - PMC9492931
OTO - NOTNLM
OT  - biomarker
OT  - diabetic retinopathy
OT  - enzyme-linked immunosorbent assay
OT  - metabolomics
OT  - non-proliferative diabetic retinopathy
OT  - proliferative diabetic retinopathy
OT  - targeted metabolomics
OT  - type 2 diabetes
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/27 06:00
MHDA- 2022/09/28 06:00
PMCR- 2022/01/01
CRDT- 2022/09/26 17:09
PHST- 2022/07/04 00:00 [received]
PHST- 2022/08/23 00:00 [accepted]
PHST- 2022/09/26 17:09 [entrez]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2022.986303 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2022 Sep 8;13:986303. doi: 
      10.3389/fendo.2022.986303. eCollection 2022.