Novel Serum and Urinary Metabolites Associated with Diabetic Retinopathy in Three Asian Cohorts

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004–11) representing three major Asian ethnic groups (aged 40–80 years:...

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Veröffentlicht in:Metabolites Jg. 11; H. 9; S. 614
Hauptverfasser: Quek, Debra Q. Y., He, Feng, Sultana, Rehena, Banu, Riswana, Chee, Miao Li, Nusinovici, Simon, Thakur, Sahil, Qian, Chaoxu, Cheng, Ching-Yu, Wong, Tien Y., Sabanayagam, Charumathi
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basel MDPI AG 09.09.2021
MDPI
Schlagworte:
Amino acids
Blood pressure
Cholesterol
Citric acid
Creatinine
Cross-sectional studies
cross-sectional study
Diabetes
Diabetes mellitus
Diabetic retinopathy
Esters
Ethanolamine
Glycolysis
Hypoxanthine
Lipid metabolism
Lipids
Lipoproteins
Mass spectrometry
Metabolic disorders
Metabolism
Metabolites
Microvasculature
Minority & ethnic groups
NMR
Nuclear magnetic resonance
nuclear magnetic resonance spectroscopy
Plasma
Population studies
Regression analysis
Retinopathy
Risk factors
Scientific imaging
serum/plasma metabolites
Spectroscopy
Tyrosine
urinary metabolites
Urine
Singapore
ISSN:2218-1989, 2218-1989
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Abstract Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004–11) representing three major Asian ethnic groups (aged 40–80 years: Chinese, 592; Malays, 1052; Indians, 1320) was performed. A panel of 228 serum/plasma metabolites and 54 urinary metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Main outcomes were defined as any DR, moderate/above DR, and vision-threatening DR assessed from retinal photographs. The relationship between metabolites and DR outcomes was assessed using multivariate logistic regression models, and metabolites significant after Bonferroni correction were meta-analyzed. Among serum/plasma metabolites, lower levels of tyrosine and cholesterol esters to total lipids ratio in IDL and higher levels of creatinine were positively associated with all three outcomes of DR (all p < 0.005). Among urinary metabolites, lower levels of citrate, ethanolamine, formate, and hypoxanthine were positively associated with all three DR outcomes (all p < 0.005). Higher levels of serum/plasma 3-hydroxybutyrate and lower levels of urinary 3-hydroxyisobutyrate were associated with VTDR. Comprehensive metabolic profiling in three large Asian cohorts with DR demonstrated alterations in serum/plasma and urinary metabolites mostly related to amino acids, lipoprotein subclasses, kidney function, and glycolysis.
AbstractList Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004–11) representing three major Asian ethnic groups (aged 40–80 years: Chinese, 592; Malays, 1052; Indians, 1320) was performed. A panel of 228 serum/plasma metabolites and 54 urinary metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Main outcomes were defined as any DR, moderate/above DR, and vision-threatening DR assessed from retinal photographs. The relationship between metabolites and DR outcomes was assessed using multivariate logistic regression models, and metabolites significant after Bonferroni correction were meta-analyzed. Among serum/plasma metabolites, lower levels of tyrosine and cholesterol esters to total lipids ratio in IDL and higher levels of creatinine were positively associated with all three outcomes of DR (all p < 0.005). Among urinary metabolites, lower levels of citrate, ethanolamine, formate, and hypoxanthine were positively associated with all three DR outcomes (all p < 0.005). Higher levels of serum/plasma 3-hydroxybutyrate and lower levels of urinary 3-hydroxyisobutyrate were associated with VTDR. Comprehensive metabolic profiling in three large Asian cohorts with DR demonstrated alterations in serum/plasma and urinary metabolites mostly related to amino acids, lipoprotein subclasses, kidney function, and glycolysis.
Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004-11) representing three major Asian ethnic groups (aged 40-80 years: Chinese, 592; Malays, 1052; Indians, 1320) was performed. A panel of 228 serum/plasma metabolites and 54 urinary metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Main outcomes were defined as any DR, moderate/above DR, and vision-threatening DR assessed from retinal photographs. The relationship between metabolites and DR outcomes was assessed using multivariate logistic regression models, and metabolites significant after Bonferroni correction were meta-analyzed. Among serum/plasma metabolites, lower levels of tyrosine and cholesterol esters to total lipids ratio in IDL and higher levels of creatinine were positively associated with all three outcomes of DR (all p < 0.005). Among urinary metabolites, lower levels of citrate, ethanolamine, formate, and hypoxanthine were positively associated with all three DR outcomes (all p < 0.005). Higher levels of serum/plasma 3-hydroxybutyrate and lower levels of urinary 3-hydroxyisobutyrate were associated with VTDR. Comprehensive metabolic profiling in three large Asian cohorts with DR demonstrated alterations in serum/plasma and urinary metabolites mostly related to amino acids, lipoprotein subclasses, kidney function, and glycolysis.Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004-11) representing three major Asian ethnic groups (aged 40-80 years: Chinese, 592; Malays, 1052; Indians, 1320) was performed. A panel of 228 serum/plasma metabolites and 54 urinary metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Main outcomes were defined as any DR, moderate/above DR, and vision-threatening DR assessed from retinal photographs. The relationship between metabolites and DR outcomes was assessed using multivariate logistic regression models, and metabolites significant after Bonferroni correction were meta-analyzed. Among serum/plasma metabolites, lower levels of tyrosine and cholesterol esters to total lipids ratio in IDL and higher levels of creatinine were positively associated with all three outcomes of DR (all p < 0.005). Among urinary metabolites, lower levels of citrate, ethanolamine, formate, and hypoxanthine were positively associated with all three DR outcomes (all p < 0.005). Higher levels of serum/plasma 3-hydroxybutyrate and lower levels of urinary 3-hydroxyisobutyrate were associated with VTDR. Comprehensive metabolic profiling in three large Asian cohorts with DR demonstrated alterations in serum/plasma and urinary metabolites mostly related to amino acids, lipoprotein subclasses, kidney function, and glycolysis.
Author Wong, Tien Y.
Quek, Debra Q. Y.
Sultana, Rehena
Banu, Riswana
Thakur, Sahil
Chee, Miao Li
Cheng, Ching-Yu
Sabanayagam, Charumathi
He, Feng
Qian, Chaoxu
Nusinovici, Simon
AuthorAffiliation 2 Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore; rehena.sultana@duke-nus.edu.sg
3 Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
1 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore; debra.quek@mohh.com.sg (D.Q.Y.Q.); e0215973@u.nus.edu (F.H.); riswana.banu.mohd.abdul@seri.com.sg (R.B.); chee.miao.li@seri.com.sg (M.L.C.); simon.nusinovici@seri.com.sg (S.N.); thakur.sahil@seri.com.sg (S.T.); qian.chaoxu@seri.com.sg (C.Q.); chingyu.cheng@duke-nus.edu.sg (C.-Y.C.); wong.tien.yin@singhealth.com.sg (T.Y.W.)
AuthorAffiliation_xml – name: 1 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore; debra.quek@mohh.com.sg (D.Q.Y.Q.); e0215973@u.nus.edu (F.H.); riswana.banu.mohd.abdul@seri.com.sg (R.B.); chee.miao.li@seri.com.sg (M.L.C.); simon.nusinovici@seri.com.sg (S.N.); thakur.sahil@seri.com.sg (S.T.); qian.chaoxu@seri.com.sg (C.Q.); chingyu.cheng@duke-nus.edu.sg (C.-Y.C.); wong.tien.yin@singhealth.com.sg (T.Y.W.)
– name: 2 Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore; rehena.sultana@duke-nus.edu.sg
– name: 3 Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
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Cites_doi 10.3109/09286580903144738
10.1001/archopht.1984.01040030405011
10.1016/S2213-8587(14)70146-9
10.1007/s11306-015-0774-y
10.1186/s12986-019-0358-3
10.1046/j.1464-5491.1999.00182.x
10.1111/j.1523-1755.2004.00386.x
10.1681/ASN.2013020126
10.1371/journal.pone.0097001
10.1016/j.hlc.2016.10.020
10.1002/biof.71
10.1007/s00125-018-4619-x
10.1167/iovs.17-22692
10.1167/iovs.19-27321
10.1046/j.1523-1755.2003.00712.x
10.3945/ajcn.114.101857
10.3109/07853890.2013.853369
10.1093/aje/kwx016
10.1007/s11306-015-0877-5
10.1016/j.ophtha.2017.10.026
10.1167/iovs.10-5348
10.1523/JNEUROSCI.3483-13.2014
10.1093/ije/dyaa238
10.1136/bmjdrc-2019-000877
10.3109/13813455.2011.623705
10.1021/acs.jproteome.7b00518
10.1016/j.kint.2018.11.033
10.1039/C3AN02188B
10.1289/ehp.1205657
10.1016/j.ophtha.2018.04.007
10.1161/CIRCRESAHA.110.223545
10.4093/dmj.2015.39.5.353
10.2337/diacare.26.2007.S83
10.1152/ajprenal.00463.2017
10.1515/cclm-2012-0552
10.1016/j.clinbiochem.2014.09.009
10.3945/ajcn.114.092601
10.1016/j.biopha.2006.09.012
10.2337/db15-0661
10.3390/ijms17122035
10.3390/nu11050998
10.2337/dc16-2641
10.1053/meta.2002.32804
10.1016/S0140-6736(98)07019-6
10.1007/s00125-015-3730-5
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References Cupisti (ref_45) 2007; 61
Badeau (ref_15) 2014; 46
Remer (ref_23) 2014; 47
Wurtz (ref_14) 2017; 186
Pinto (ref_19) 2014; 139
ref_36
ref_13
ref_12
ref_34
ref_10
Adler (ref_29) 2003; 63
ref_32
Haid (ref_22) 2017; 17
Welsh (ref_28) 2018; 61
Abate (ref_43) 2004; 65
Ma (ref_39) 2015; 101
Majithia (ref_17) 2021; 50
Forouhi (ref_35) 2014; 2
Aung (ref_26) 2014; 34
Zhao (ref_33) 2017; 26
Solomon (ref_2) 2017; 40
Siegert (ref_6) 2002; 51
Parhofer (ref_5) 2015; 39
Lemaitre (ref_38) 2015; 101
Hebels (ref_24) 2013; 121
Tan (ref_18) 2018; 125
Lankinen (ref_37) 2015; 58
Sumarriva (ref_11) 2019; 60
Lamarre (ref_41) 2013; 51
Chen (ref_8) 2016; 65
ref_25
Williams (ref_40) 2010; 36
ref_20
Kim (ref_27) 2018; 59
Sharma (ref_46) 2013; 24
ref_1
Barba (ref_7) 2010; 51
Giacco (ref_4) 2010; 107
Lavanya (ref_16) 2009; 16
Klein (ref_30) 1984; 102
Munipally (ref_9) 2011; 117
Goraya (ref_44) 2019; 95
Bervoets (ref_21) 2015; 11
Wong (ref_3) 2018; 125
Haffner (ref_31) 2003; 26
Goraya (ref_42) 2018; 314
References_xml – volume: 16
  start-page: 325
  year: 2009
  ident: ref_16
  article-title: Methodology of the Singapore Indian Chinese Cohort (SICC) eye study: Quantifying ethnic variations in the epidemiology of eye diseases in Asians
  publication-title: Ophthalmic Epidemiol.
  doi: 10.3109/09286580903144738
– volume: 102
  start-page: 527
  year: 1984
  ident: ref_30
  article-title: The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years
  publication-title: Arch. Ophthalmol.
  doi: 10.1001/archopht.1984.01040030405011
– volume: 2
  start-page: 810
  year: 2014
  ident: ref_35
  article-title: Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: The EPIC-InterAct case-cohort study
  publication-title: Lancet Diabetes Endocrinol.
  doi: 10.1016/S2213-8587(14)70146-9
– volume: 11
  start-page: 1197
  year: 2015
  ident: ref_21
  article-title: Influence of preanalytical sampling conditions on the 1H NMR metabolic profile of human blood plasma and introduction of the Standard PREanalytical Code used in biobanking
  publication-title: Metabolomics
  doi: 10.1007/s11306-015-0774-y
– ident: ref_12
  doi: 10.1186/s12986-019-0358-3
– ident: ref_32
  doi: 10.1046/j.1464-5491.1999.00182.x
– volume: 65
  start-page: 386
  year: 2004
  ident: ref_43
  article-title: The metabolic syndrome and uric acid nephrolithiasis: Novel features of renal manifestation of insulin resistance
  publication-title: Kidney Int.
  doi: 10.1111/j.1523-1755.2004.00386.x
– volume: 24
  start-page: 1901
  year: 2013
  ident: ref_46
  article-title: Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease
  publication-title: J. Am. Soc. Nephrol.
  doi: 10.1681/ASN.2013020126
– ident: ref_34
  doi: 10.1371/journal.pone.0097001
– volume: 26
  start-page: 211
  year: 2017
  ident: ref_33
  article-title: Analysis of Lipoprotein Subfractions in 920 Patients With and Without Type 2 Diabetes
  publication-title: Heart Lung Circ.
  doi: 10.1016/j.hlc.2016.10.020
– volume: 36
  start-page: 19
  year: 2010
  ident: ref_40
  article-title: Homocysteine metabolism and its relation to health and disease
  publication-title: Biofactors
  doi: 10.1002/biof.71
– volume: 61
  start-page: 1581
  year: 2018
  ident: ref_28
  article-title: Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: Results from the ADVANCE trial
  publication-title: Diabetologia
  doi: 10.1007/s00125-018-4619-x
– volume: 59
  start-page: 572
  year: 2018
  ident: ref_27
  article-title: Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
  publication-title: Investig. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.17-22692
– volume: 60
  start-page: 3119
  year: 2019
  ident: ref_11
  article-title: Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy
  publication-title: Invest. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.19-27321
– volume: 63
  start-page: 225
  year: 2003
  ident: ref_29
  article-title: Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64)
  publication-title: Kidney Int.
  doi: 10.1046/j.1523-1755.2003.00712.x
– volume: 101
  start-page: 1047
  year: 2015
  ident: ref_38
  article-title: Plasma phospholipid very-long-chain saturated fatty acids and incident diabetes in older adults: The Cardiovascular Health Study
  publication-title: Am. J. Clin. Nutr.
  doi: 10.3945/ajcn.114.101857
– volume: 46
  start-page: 18
  year: 2014
  ident: ref_15
  article-title: Systemic metabolic markers and myocardial glucose uptake in type 2 diabetic and coronary artery disease patients treated for 16 weeks with rosiglitazone, a PPARgamma agonist
  publication-title: Ann. Med.
  doi: 10.3109/07853890.2013.853369
– volume: 186
  start-page: 1084
  year: 2017
  ident: ref_14
  article-title: Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Large-Scale Epidemiology: A Primer on -Omic Technologies
  publication-title: Am. J. Epidemiol.
  doi: 10.1093/aje/kwx016
– ident: ref_10
  doi: 10.1007/s11306-015-0877-5
– volume: 125
  start-page: 529
  year: 2018
  ident: ref_18
  article-title: Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy: The Singapore Epidemiology of Eye Diseases Study
  publication-title: Ophthalmology
  doi: 10.1016/j.ophtha.2017.10.026
– volume: 51
  start-page: 4416
  year: 2010
  ident: ref_7
  article-title: Metabolic fingerprints of proliferative diabetic retinopathy: An 1H-NMR-based metabonomic approach using vitreous humor
  publication-title: Invest. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.10-5348
– ident: ref_1
– volume: 34
  start-page: 726
  year: 2014
  ident: ref_26
  article-title: Dopamine deficiency contributes to early visual dysfunction in a rodent model of type 1 diabetes
  publication-title: J. Neurosci.
  doi: 10.1523/JNEUROSCI.3483-13.2014
– volume: 50
  start-page: 41
  year: 2021
  ident: ref_17
  article-title: Cohort profile: The Singapore Epidemiology of Eye Diseases study (SEED)
  publication-title: Int. J. Epidemiol.
  doi: 10.1093/ije/dyaa238
– ident: ref_25
  doi: 10.1136/bmjdrc-2019-000877
– volume: 117
  start-page: 254
  year: 2011
  ident: ref_9
  article-title: Evaluation of indoleamine 2,3-dioxygenase expression and kynurenine pathway metabolites levels in serum samples of diabetic retinopathy patients
  publication-title: Arch. Physiol. Biochem.
  doi: 10.3109/13813455.2011.623705
– volume: 17
  start-page: 203
  year: 2017
  ident: ref_22
  article-title: Long-Term Stability of Human Plasma Metabolites during Storage at −80 °C
  publication-title: J. Proteome Res.
  doi: 10.1021/acs.jproteome.7b00518
– volume: 95
  start-page: 1190
  year: 2019
  ident: ref_44
  article-title: Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis
  publication-title: Kidney Int.
  doi: 10.1016/j.kint.2018.11.033
– volume: 139
  start-page: 1168
  year: 2014
  ident: ref_19
  article-title: Human plasma stability during handling and storage: Impact on NMR metabolomics
  publication-title: Analyst
  doi: 10.1039/C3AN02188B
– volume: 121
  start-page: 480
  year: 2013
  ident: ref_24
  article-title: Performance in omics analyses of blood samples in long-term storage: Opportunities for the exploitation of existing biobanks in environmental health research
  publication-title: Environ. Health Perspect.
  doi: 10.1289/ehp.1205657
– volume: 125
  start-page: 1608
  year: 2018
  ident: ref_3
  article-title: Guidelines on Diabetic Eye Care: The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings
  publication-title: Ophthalmology
  doi: 10.1016/j.ophtha.2018.04.007
– volume: 107
  start-page: 1058
  year: 2010
  ident: ref_4
  article-title: Oxidative stress and diabetic complications
  publication-title: Circ. Res.
  doi: 10.1161/CIRCRESAHA.110.223545
– volume: 39
  start-page: 353
  year: 2015
  ident: ref_5
  article-title: Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia
  publication-title: Diabetes Metab. J.
  doi: 10.4093/dmj.2015.39.5.353
– volume: 26
  start-page: S83
  year: 2003
  ident: ref_31
  article-title: Management of dyslipidemia in adults with diabetes
  publication-title: Diabetes Care
  doi: 10.2337/diacare.26.2007.S83
– volume: 314
  start-page: F985
  year: 2018
  ident: ref_42
  article-title: Acid retention in chronic kidney disease is inversely related to GFR
  publication-title: Am. J. Physiol. Renal. Physiol.
  doi: 10.1152/ajprenal.00463.2017
– volume: 51
  start-page: 571
  year: 2013
  ident: ref_41
  article-title: Formate: An essential metabolite, a biomarker, or more?
  publication-title: Clin. Chem. Lab. Med.
  doi: 10.1515/cclm-2012-0552
– volume: 47
  start-page: 307
  year: 2014
  ident: ref_23
  article-title: Long-term urine biobanking: Storage stability of clinical chemical parameters under moderate freezing conditions without use of preservatives
  publication-title: Clin. Biochem.
  doi: 10.1016/j.clinbiochem.2014.09.009
– volume: 101
  start-page: 153
  year: 2015
  ident: ref_39
  article-title: Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: The Cardiovascular Health Study
  publication-title: Am. J. Clin. Nutr.
  doi: 10.3945/ajcn.114.092601
– volume: 61
  start-page: 86
  year: 2007
  ident: ref_45
  article-title: Insulin resistance and low urinary citrate excretion in calcium stone formers
  publication-title: Biomed. Pharmacother.
  doi: 10.1016/j.biopha.2006.09.012
– volume: 65
  start-page: 1099
  year: 2016
  ident: ref_8
  article-title: Plasma Metabonomic Profiling of Diabetic Retinopathy
  publication-title: Diabetes
  doi: 10.2337/db15-0661
– ident: ref_20
  doi: 10.3390/ijms17122035
– ident: ref_36
  doi: 10.3390/nu11050998
– volume: 40
  start-page: 412
  year: 2017
  ident: ref_2
  article-title: Diabetic Retinopathy: A Position Statement by the American Diabetes Association
  publication-title: Diabetes Care
  doi: 10.2337/dc16-2641
– volume: 51
  start-page: 743
  year: 2002
  ident: ref_6
  article-title: Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes
  publication-title: Metabolism
  doi: 10.1053/meta.2002.32804
– ident: ref_13
  doi: 10.1016/S0140-6736(98)07019-6
– volume: 58
  start-page: 2533
  year: 2015
  ident: ref_37
  article-title: Plasma fatty acids as predictors of glycaemia and type 2 diabetes
  publication-title: Diabetologia
  doi: 10.1007/s00125-015-3730-5
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Snippet Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains...
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SubjectTerms Amino acids
Blood pressure
Cholesterol
Citric acid
Creatinine
Cross-sectional studies
cross-sectional study
Diabetes
Diabetes mellitus
Diabetic retinopathy
Esters
Ethanolamine
Glycolysis
Hypoxanthine
Lipid metabolism
Lipids
Lipoproteins
Mass spectrometry
Metabolic disorders
Metabolism
Metabolites
Microvasculature
Minority & ethnic groups
NMR
Nuclear magnetic resonance
nuclear magnetic resonance spectroscopy
Plasma
Population studies
Regression analysis
Retinopathy
Risk factors
Scientific imaging
serum/plasma metabolites
Spectroscopy
Tyrosine
urinary metabolites
Urine
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Title Novel Serum and Urinary Metabolites Associated with Diabetic Retinopathy in Three Asian Cohorts
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