Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study
Abstract Background Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and causes vision impairment and blindness. The presence of major risk factors for DR, such as high levels of HbA1c, does not predict all DR pathogenesis in the clinic, which suggests that uncove...
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BMC
2024-12-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-024-02535-1 |
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| _version_ | 1846112888832393216 |
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| author | Xingchen Zhou Guixue Hou Xin Wang Zhaoyi Peng Xiaoming Yin Jing Yang Shan Wang Yayi He Yue Wang Jing Sui Wei Qiang Hui Guo Yanan Wang Liang Lin Bingyin Shi Mingqian He |
| author_facet | Xingchen Zhou Guixue Hou Xin Wang Zhaoyi Peng Xiaoming Yin Jing Yang Shan Wang Yayi He Yue Wang Jing Sui Wei Qiang Hui Guo Yanan Wang Liang Lin Bingyin Shi Mingqian He |
| author_sort | Xingchen Zhou |
| collection | DOAJ |
| description | Abstract Background Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and causes vision impairment and blindness. The presence of major risk factors for DR, such as high levels of HbA1c, does not predict all DR pathogenesis in the clinic, which suggests that uncovering the underlying mechanisms and identifying novel markers are needed. Previous evidence has shown that the serum metabolic signature of DR is unique and detectable compared with that of diabetes mellitus (DM). Here, we aimed to identify serum metabolites as reliable biomarkers for the presence of DR in type 2 DM (T2DM) patients. Methods We performed untargeted and targeted metabolomic studies using liquid chromatography‒mass spectrometry (LC‒MS) and multiple reaction monitoring (MRM) methods on the serum samples of T2DM patients. For the discovery dataset, 39 DR patients and 39 non-DR (NDR) patients were included. For the validation dataset, 95 DR patients and 95 non-DR (NDR) patients were included. Receiver operating characteristic curve analysis was performed to evaluate the discriminating power of the metabolites. Binary logistic regression models were fit to evaluate the associations of metabolite peak areas or neurotransmitter concentrations with the presence of DR and adjusted for known risk factors. Results A total of 7123 metabolites were tested. The 39 DR patients had a mean age of 56 years with an average diabetes duration of 12 years, and the 39 NDR patients had a mean age of 57 years with an average diabetes duration of 11 years. Nine serum candidate markers were further identified. Six out of nine markers were associated with DR after we adjusted for covariates, including blood pressure, HbA1c, diabetes duration, fasting blood glucose, triglyceride, eGFR etc. Among them, eicosapentaenoic acid (EPA) and L-tyrosine were validated in an independent, risk factor-matched sample set. The serum L-tyrosine concentration was decreased in DR group by 47% (-0.22 ± 0.87 vs. 0.48 ± 1.05, P < 0.001), of which the cutoff value was 0.10 mg/ml, with 86% sensitivity and 40% specificity (AUC = 0.62, 95% CI = 0.54–0.70, P = 0.005). Conclusions Low levels of circulating L-Tyrosine indicate retinopathy occurrence in T2DM population. |
| format | Article |
| id | doaj-art-ed1f2d87d4fe4e61930a0f7bdeeae717 |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-ed1f2d87d4fe4e61930a0f7bdeeae7172024-12-22T12:12:57ZengBMCCardiovascular Diabetology1475-28402024-12-0123111110.1186/s12933-024-02535-1Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional studyXingchen Zhou0Guixue Hou1Xin Wang2Zhaoyi Peng3Xiaoming Yin4Jing Yang5Shan Wang6Yayi He7Yue Wang8Jing Sui9Wei Qiang10Hui Guo11Yanan Wang12Liang Lin13Bingyin Shi14Mingqian He15Department of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityBGI-SHENZHENMed-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi’an JiaoTong University, Xi’an JiaoTong universityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityChengdu HuiXin Life TechnologyDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityMed-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi’an JiaoTong University, Xi’an JiaoTong universityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityDepartment of Endocrinology and International Medical Center, The First Affiliated Hospital of Xi’an JiaoTong UniversityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityBGI-SHENZHENDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityDepartment of Endocrinology, The First Affiliated Hospital of Xi’an JiaoTong UniversityAbstract Background Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and causes vision impairment and blindness. The presence of major risk factors for DR, such as high levels of HbA1c, does not predict all DR pathogenesis in the clinic, which suggests that uncovering the underlying mechanisms and identifying novel markers are needed. Previous evidence has shown that the serum metabolic signature of DR is unique and detectable compared with that of diabetes mellitus (DM). Here, we aimed to identify serum metabolites as reliable biomarkers for the presence of DR in type 2 DM (T2DM) patients. Methods We performed untargeted and targeted metabolomic studies using liquid chromatography‒mass spectrometry (LC‒MS) and multiple reaction monitoring (MRM) methods on the serum samples of T2DM patients. For the discovery dataset, 39 DR patients and 39 non-DR (NDR) patients were included. For the validation dataset, 95 DR patients and 95 non-DR (NDR) patients were included. Receiver operating characteristic curve analysis was performed to evaluate the discriminating power of the metabolites. Binary logistic regression models were fit to evaluate the associations of metabolite peak areas or neurotransmitter concentrations with the presence of DR and adjusted for known risk factors. Results A total of 7123 metabolites were tested. The 39 DR patients had a mean age of 56 years with an average diabetes duration of 12 years, and the 39 NDR patients had a mean age of 57 years with an average diabetes duration of 11 years. Nine serum candidate markers were further identified. Six out of nine markers were associated with DR after we adjusted for covariates, including blood pressure, HbA1c, diabetes duration, fasting blood glucose, triglyceride, eGFR etc. Among them, eicosapentaenoic acid (EPA) and L-tyrosine were validated in an independent, risk factor-matched sample set. The serum L-tyrosine concentration was decreased in DR group by 47% (-0.22 ± 0.87 vs. 0.48 ± 1.05, P < 0.001), of which the cutoff value was 0.10 mg/ml, with 86% sensitivity and 40% specificity (AUC = 0.62, 95% CI = 0.54–0.70, P = 0.005). Conclusions Low levels of circulating L-Tyrosine indicate retinopathy occurrence in T2DM population.https://doi.org/10.1186/s12933-024-02535-1BiomarkersMetabolite biomarkersLiquid chromatography-mass spectrometryDiabetic retinopathyDiabetes mellitus, type 2Eicosapentaenoic acid |
| spellingShingle | Xingchen Zhou Guixue Hou Xin Wang Zhaoyi Peng Xiaoming Yin Jing Yang Shan Wang Yayi He Yue Wang Jing Sui Wei Qiang Hui Guo Yanan Wang Liang Lin Bingyin Shi Mingqian He Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study Cardiovascular Diabetology Biomarkers Metabolite biomarkers Liquid chromatography-mass spectrometry Diabetic retinopathy Diabetes mellitus, type 2 Eicosapentaenoic acid |
| title | Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study |
| title_full | Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study |
| title_fullStr | Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study |
| title_full_unstemmed | Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study |
| title_short | Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study |
| title_sort | metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two chinese datasets with type 2 diabetes a cross sectional study |
| topic | Biomarkers Metabolite biomarkers Liquid chromatography-mass spectrometry Diabetic retinopathy Diabetes mellitus, type 2 Eicosapentaenoic acid |
| url | https://doi.org/10.1186/s12933-024-02535-1 |
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