Research progress on the relationship between homocysteine, uric acid and diabetic retinopathy_West China Medical Journal

Authors：

RAN Qibo , LEI Chunyan ,  ZHANG Meixia

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

ZHANG Meixia, Email: zhangmeixia@scu.edu.cn

Keywords：

Homocysteine; uric acid; diabetes; diabetic retinopathy

DOI：

10.7507/1002-0179.202304104

Video：

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Diabetic retinopathy is a vascular complication of diabetes, and homocysteine is an intermediate product of methionine metabolism. Hyperhomocysteinemia can directly or indirectly damage vascular endothelial cells, causing vascular endothelial cells dysfunction and participating in the occurrence and development of diabetic retinopathy. Uric acid is the final product of purine metabolism. Hyperuricemia can cause vascular endothelial dysfunction, oxidative metabolism, platelet adhesion and aggregation dysfunction, thus participating in the occurrence and development of diabetic retinopathy. In recent years, there have been many studies on the correlation between diabetic retinopathy and levels of homocysteine and uric acid. This article reviews the relevant literature at home and abroad in order to provide new information for the prevention and treatment of diabetic retinopathy.

Citation： RAN Qibo, LEI Chunyan, ZHANG Meixia. Research progress on the relationship between homocysteine, uric acid and diabetic retinopathy. West China Medical Journal, 2023, 38(12): 1924-1928. doi: 10.7507/1002-0179.202304104 Copy

1.	Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract, 2019, 157: 107843.
2.	Lin KY, Hsih WH, Lin YB, et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig, 2021, 12(8): 1322-1325.
3.	Crasto W, Patel V, Davies MJ, et al. Prevention of microvascular complications of diabetes. Endocrinol Metab Clin North Am, 2021, 50(3): 431-455.
4.	Tawfik A, Mohamed R, Elsherbiny NM, et al. Homocysteine: a potential biomarker for diabetic retinopathy. J Clin Med, 2019, 8(1): 121.
5.	Sharaf El Din UAA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: a review. J Adv Res, 2017, 8(5): 537-548.
6.	Xiong Q, Liu J, Xu Y. Effects of uric acid on diabetes mellitus and its chronic complications. Int J Endocrinol, 2019, 2019: 9691345.
7.	Kinuthia UM, Wolf A, Langmann T. Microglia and inflammatory responses in diabetic retinopathy. Front Immunol, 2020, 11: 564077.
8.	魏静, 张金成, 史亚男, 等. 2 型糖尿病视网膜病变患者同型半胱氨酸和血尿酸水平及其预测价值. 中华眼底病杂志, 2023, 39(2): 125-131.
9.	Agardh E, Hultberg B, Agardh CD. Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine. Scand J Clin Lab Invest, 2000, 60(3): 169-174.
10.	Nguyen TT, Alibrahim E, Islam FM, et al. Inflammatory, hemostatic, and other novel biomarkers for diabetic retinopathy: the multi-ethnic study of atherosclerosis. Diabetes Care, 2009, 32(9): 1704-1709.
11.	de Luis DA, Fernandez N, Arranz ML, et al. Total homocysteine levels relation with chronic complications of diabetes, body composition, and other cardiovascular risk factors in a population of patients with diabetes mellitus type 2. J Diabetes Complications, 2005, 19(1): 42-46.
12.	Agulló-Ortuño MT, Albaladejo MD, Parra S, et al. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta, 2002, 326(1/2): 105-112.
13.	Saeed BO, Nixon SJ, White AJ, et al. Fasting homocysteine levels in adults with type 1 diabetes and retinopathy. Clin Chim Acta, 2004, 341(1/2): 27-32.
14.	Bulum T, Blaslov K, Duvnjak L. Plasma homocysteine is associated with retinopathy in type 1 diabetic patients in the absence of nephropathy. Semin Ophthalmol, 2016, 31(3): 198-202.
15.	Hoogeveen EK, Kostense PJ, Eysink PE, et al. Hyperhomocysteinemia is associated with the presence of retinopathy in type 2 diabetes mellitus: the Hoorn study. Arch Intern Med, 2000, 160(19): 2984-2990.
16.	Cho HC. The relationship among homocysteine, bilirubin, and diabetic retinopathy. Diabetes Metab J, 2011, 35(6): 595-601.
17.	Aydin E, Demir HD, Ozyurt H, et al. Association of plasma homocysteine and macular edema in type 2 diabetes mellitus. Eur J Ophthalmol, 2008, 18(2): 226-232.
18.	杨国庆, 陆菊明, 潘长玉. 血浆同型半胱氨酸浓度与 2 型糖尿病视网膜病变的关系. 中华内科杂志, 2002(1): 37-41.
19.	Brazionis L, Rowley K Sr, Itsiopoulos C, et al. Homocysteine and diabetic retinopathy. Diabetes Care, 2008, 31(1): 50-56.
20.	Huang EJ, Kuo WW, Chen YJ, et al. Homocysteine and other biochemical parameters in type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy. Clin Chim Acta, 2006, 366(1/2): 293-298.
21.	Goldstein M, Leibovitch I, Yeffimov I, et al. Hyperhomocysteinemia in patients with diabetes mellitus with and without diabetic retinopathy. Eye (Lond), 2004, 18(5): 460-465.
22.	李思佳, 张涤, 任永波, 等. 增殖性糖尿病性视网膜病变患者血清, 房水, 玻璃体中的同型半胱氨酸定量测定及相关性分析. 黑龙江医药科学, 2013, 36(2): 63-64.
23.	Lim CP, Loo AV, Khaw KW, et al. Plasma, aqueous and vitreous homocysteine levels in proliferative diabetic retinopathy. Br J Ophthalmol, 2012, 96(5): 704-707.
24.	Aydemir O, Türkçüoğlu P, Güler M, et al. Plasma and vitreous homocysteine concentrations in patients with proliferative diabetic retinopathy. Retina, 2008, 28(5): 741-743.
25.	Au-Yeung KK, Woo CW, Sung FL, et al. Hyperhomocysteinemia activates nuclear factor-kappa B in endothelial cells via oxidative stress. Circ Res, 2004, 94(1): 28-36.
26.	Poddar R, Sivasubramanian N, DiBello PM, et al. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation, 2001, 103(22): 2717-2723.
27.	Dong N, Shi H, Tang X. Plasma homocysteine levels are associated with macular thickness in type 2 diabetes without diabetic macular edema. Int Ophthalmol, 2018, 38(2): 737-746.
28.	Xia Q, Zhang SH, Yang SM, et al. Serum uric acid is independently associated with diabetic nephropathy but not diabetic retinopathy in patients with type 2 diabetes mellitus. J Chin Med Assoc, 2020, 83(4): 350-356.
29.	Navin S, Krishnamurthy N, Ashakiran S, et al. The association of hypomagnesaemia, high normal uricaemia and dyslipidaemia in the patients with diabetic retinopathy. J Clin Diagn Res, 2013, 7(9): 1852-1854.
30.	Kuwata H, Okamura S, Hayashino Y, et al. Serum uric acid levels are associated with increased risk of newly developed diabetic retinopathy among Japanese male patients with type 2 diabetes: a prospective cohort study (diabetes distress and care registry at Tenri [DDCRT 13]). Diabetes Metab Res Rev, 2017, 33(7): 2905.
31.	Cui J, Ren JP, Chen DN, et al. Prevalence and associated factors of diabetic retinopathy in Beijing, China: a cross-sectional study. BMJ Open, 2017, 7(8): e015473.
32.	Chuengsamarn S, Rattanamongkolgul S, Jirawatnotai S. Association between serum uric acid level and microalbuminuria to chronic vascular complications in Thai patients with type 2 diabetes. J Diabetes Complications, 2014, 28(2): 124-129.
33.	Hou L, Shi Y, Wang S, et al. Associations of serum uric acid level with diabetic retinopathy and albuminuria in patients with type 2 diabetes mellitus. J Int Med Res, 2020, 48(12): 300060520963980.
34.	Chen D, Sun X, Zhao X, et al. Associations of serum uric acid and urinary albumin with the severity of diabetic retinopathy in individuals with type 2 diabetes. BMC Ophthalmol, 2020, 20(1): 467.
35.	Lee JJ, Yang IH, Kuo HK, et al. Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan--a 3-year prospective study. Diabetes Res Clin Pract, 2014, 106(2): 366-372.
36.	Xia J, Wang Z, Zhang F. Association between related purine metabolites and diabetic retinopathy in type 2 diabetic patients. Int J Endocrinol, 2014, 2014: 651050.
37.	Krizova L, Kalousova M, Kubena A, et al. Increased uric acid and glucose concentrations in vitreous and serum of patients with diabetic macular oedema. Ophthalmic Res, 2011, 46(2): 73-79.
38.	Krizova L, Kalousova M, Kubena AA, et al. Correlation of vitreous vascular endothelial growth factor and uric acid concentration using optical coherence tomography in diabetic macular edema. J Ophthalmol, 2015, 2015: 478509.
39.	Thounaojam MC, Montemari A, Powell FL, et al. Monosodium urate contributes to retinal inflammation and progression of diabetic retinopathy. Diabetes, 2019, 68(5): 1014-1025.
40.	佘新平, 朱丹丹, 郑志. 尿酸在糖尿病视网膜病变中的作用研究现状及进展. 中华眼底病杂志, 2018, 34(4): 401-404.
41.	Yu S, Hong Q, Wang Y, et al. High concentrations of uric acid inhibit angiogenesis via regulation of the Krüppel-like factor 2-vascular endothelial growth factor-A axis by miR-92a. Circ J, 2015, 79(11): 2487-2498.
42.	Capsoni F, Ongari AM, Reali E, et al. Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells. Arthritis Res Ther, 2009, 11(5): R151.

1. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract, 2019, 157: 107843.
2. Lin KY, Hsih WH, Lin YB, et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig, 2021, 12(8): 1322-1325.
3. Crasto W, Patel V, Davies MJ, et al. Prevention of microvascular complications of diabetes. Endocrinol Metab Clin North Am, 2021, 50(3): 431-455.
4. Tawfik A, Mohamed R, Elsherbiny NM, et al. Homocysteine: a potential biomarker for diabetic retinopathy. J Clin Med, 2019, 8(1): 121.
5. Sharaf El Din UAA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: a review. J Adv Res, 2017, 8(5): 537-548.
6. Xiong Q, Liu J, Xu Y. Effects of uric acid on diabetes mellitus and its chronic complications. Int J Endocrinol, 2019, 2019: 9691345.
7. Kinuthia UM, Wolf A, Langmann T. Microglia and inflammatory responses in diabetic retinopathy. Front Immunol, 2020, 11: 564077.
8. 魏静, 张金成, 史亚男, 等. 2 型糖尿病视网膜病变患者同型半胱氨酸和血尿酸水平及其预测价值. 中华眼底病杂志, 2023, 39(2): 125-131.
9. Agardh E, Hultberg B, Agardh CD. Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine. Scand J Clin Lab Invest, 2000, 60(3): 169-174.
10. Nguyen TT, Alibrahim E, Islam FM, et al. Inflammatory, hemostatic, and other novel biomarkers for diabetic retinopathy: the multi-ethnic study of atherosclerosis. Diabetes Care, 2009, 32(9): 1704-1709.
11. de Luis DA, Fernandez N, Arranz ML, et al. Total homocysteine levels relation with chronic complications of diabetes, body composition, and other cardiovascular risk factors in a population of patients with diabetes mellitus type 2. J Diabetes Complications, 2005, 19(1): 42-46.
12. Agulló-Ortuño MT, Albaladejo MD, Parra S, et al. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta, 2002, 326(1/2): 105-112.
13. Saeed BO, Nixon SJ, White AJ, et al. Fasting homocysteine levels in adults with type 1 diabetes and retinopathy. Clin Chim Acta, 2004, 341(1/2): 27-32.
14. Bulum T, Blaslov K, Duvnjak L. Plasma homocysteine is associated with retinopathy in type 1 diabetic patients in the absence of nephropathy. Semin Ophthalmol, 2016, 31(3): 198-202.
15. Hoogeveen EK, Kostense PJ, Eysink PE, et al. Hyperhomocysteinemia is associated with the presence of retinopathy in type 2 diabetes mellitus: the Hoorn study. Arch Intern Med, 2000, 160(19): 2984-2990.
16. Cho HC. The relationship among homocysteine, bilirubin, and diabetic retinopathy. Diabetes Metab J, 2011, 35(6): 595-601.
17. Aydin E, Demir HD, Ozyurt H, et al. Association of plasma homocysteine and macular edema in type 2 diabetes mellitus. Eur J Ophthalmol, 2008, 18(2): 226-232.
18. 杨国庆, 陆菊明, 潘长玉. 血浆同型半胱氨酸浓度与 2 型糖尿病视网膜病变的关系. 中华内科杂志, 2002(1): 37-41.
19. Brazionis L, Rowley K Sr, Itsiopoulos C, et al. Homocysteine and diabetic retinopathy. Diabetes Care, 2008, 31(1): 50-56.
20. Huang EJ, Kuo WW, Chen YJ, et al. Homocysteine and other biochemical parameters in type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy. Clin Chim Acta, 2006, 366(1/2): 293-298.
21. Goldstein M, Leibovitch I, Yeffimov I, et al. Hyperhomocysteinemia in patients with diabetes mellitus with and without diabetic retinopathy. Eye (Lond), 2004, 18(5): 460-465.
22. 李思佳, 张涤, 任永波, 等. 增殖性糖尿病性视网膜病变患者血清, 房水, 玻璃体中的同型半胱氨酸定量测定及相关性分析. 黑龙江医药科学, 2013, 36(2): 63-64.
23. Lim CP, Loo AV, Khaw KW, et al. Plasma, aqueous and vitreous homocysteine levels in proliferative diabetic retinopathy. Br J Ophthalmol, 2012, 96(5): 704-707.
24. Aydemir O, Türkçüoğlu P, Güler M, et al. Plasma and vitreous homocysteine concentrations in patients with proliferative diabetic retinopathy. Retina, 2008, 28(5): 741-743.
25. Au-Yeung KK, Woo CW, Sung FL, et al. Hyperhomocysteinemia activates nuclear factor-kappa B in endothelial cells via oxidative stress. Circ Res, 2004, 94(1): 28-36.
26. Poddar R, Sivasubramanian N, DiBello PM, et al. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation, 2001, 103(22): 2717-2723.
27. Dong N, Shi H, Tang X. Plasma homocysteine levels are associated with macular thickness in type 2 diabetes without diabetic macular edema. Int Ophthalmol, 2018, 38(2): 737-746.
28. Xia Q, Zhang SH, Yang SM, et al. Serum uric acid is independently associated with diabetic nephropathy but not diabetic retinopathy in patients with type 2 diabetes mellitus. J Chin Med Assoc, 2020, 83(4): 350-356.
29. Navin S, Krishnamurthy N, Ashakiran S, et al. The association of hypomagnesaemia, high normal uricaemia and dyslipidaemia in the patients with diabetic retinopathy. J Clin Diagn Res, 2013, 7(9): 1852-1854.
30. Kuwata H, Okamura S, Hayashino Y, et al. Serum uric acid levels are associated with increased risk of newly developed diabetic retinopathy among Japanese male patients with type 2 diabetes: a prospective cohort study (diabetes distress and care registry at Tenri [DDCRT 13]). Diabetes Metab Res Rev, 2017, 33(7): 2905.
31. Cui J, Ren JP, Chen DN, et al. Prevalence and associated factors of diabetic retinopathy in Beijing, China: a cross-sectional study. BMJ Open, 2017, 7(8): e015473.
32. Chuengsamarn S, Rattanamongkolgul S, Jirawatnotai S. Association between serum uric acid level and microalbuminuria to chronic vascular complications in Thai patients with type 2 diabetes. J Diabetes Complications, 2014, 28(2): 124-129.
33. Hou L, Shi Y, Wang S, et al. Associations of serum uric acid level with diabetic retinopathy and albuminuria in patients with type 2 diabetes mellitus. J Int Med Res, 2020, 48(12): 300060520963980.
34. Chen D, Sun X, Zhao X, et al. Associations of serum uric acid and urinary albumin with the severity of diabetic retinopathy in individuals with type 2 diabetes. BMC Ophthalmol, 2020, 20(1): 467.
35. Lee JJ, Yang IH, Kuo HK, et al. Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan--a 3-year prospective study. Diabetes Res Clin Pract, 2014, 106(2): 366-372.
36. Xia J, Wang Z, Zhang F. Association between related purine metabolites and diabetic retinopathy in type 2 diabetic patients. Int J Endocrinol, 2014, 2014: 651050.
37. Krizova L, Kalousova M, Kubena A, et al. Increased uric acid and glucose concentrations in vitreous and serum of patients with diabetic macular oedema. Ophthalmic Res, 2011, 46(2): 73-79.
38. Krizova L, Kalousova M, Kubena AA, et al. Correlation of vitreous vascular endothelial growth factor and uric acid concentration using optical coherence tomography in diabetic macular edema. J Ophthalmol, 2015, 2015: 478509.
39. Thounaojam MC, Montemari A, Powell FL, et al. Monosodium urate contributes to retinal inflammation and progression of diabetic retinopathy. Diabetes, 2019, 68(5): 1014-1025.
40. 佘新平, 朱丹丹, 郑志. 尿酸在糖尿病视网膜病变中的作用研究现状及进展. 中华眼底病杂志, 2018, 34(4): 401-404.
41. Yu S, Hong Q, Wang Y, et al. High concentrations of uric acid inhibit angiogenesis via regulation of the Krüppel-like factor 2-vascular endothelial growth factor-A axis by miR-92a. Circ J, 2015, 79(11): 2487-2498.
42. Capsoni F, Ongari AM, Reali E, et al. Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells. Arthritis Res Ther, 2009, 11(5): R151.

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