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DOI: 10.1055/a-2441-5132
Association of Circulating Homocysteine Level with the Risk of Nephropathy in Type 2 Diabetes Mellitus: A Meta-Analysis
Supported by: The Natural Science Foundation Project of the Xinjiang Uygur Autonomous Region 2019D01C189Abstract
The objective of the study was to explore the association between homocysteine (Hcy) levels and the risk of type 2 diabetic nephropathy (T2DN). PubMed, Web of Science, Cochrane Library, and Embase databases were searched to collect literature on the association between Hcy levels and the risk of T2DN. The retrieval period was from the establishment of the database to September 10, 2024. Stata 15.0 statistical software was used for data analysis. Type II diabetes without nephropathy was considered the control group, and microalbuminuria and macroalbuminuria were included in the experimental group. Fourteen articles were included in this meta-analysis. The results of the meta-analysis showed that compared with the control group, the level of Hcy in the T2DN group with microalbuminuria [Weighted mean difference (WMD)=2.50, 95% confidence interval (CI): 1.49–3.51, p<0.001] and the group with macroalbuminuria (WMD=3.38, 95% CI: 1.95–4.82) was significantly increased. Compared with the T2DN microalbuminuria group, the Hcy level in the T2DN macroalbuminuria group was considerably higher (WMD=2.12, 95% CI: 0.80–3.44, p<0.001). High homocysteine levels were associated with an increased risk of T2DN (OR=1.36, 95% CI: 1.20–1.54, p<0.001). In conclusion, circulating Hcy levels are significantly associated with the severity of T2DN. In addition, there was a significant association between high Hcy levels and an increased risk of T2DN.
Publication History
Received: 13 September 2024
Accepted after revision: 11 October 2024
Article published online:
21 November 2024
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References
- 1 Lin YC, Chang YH, Yang SY. et al. Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc 2018; 117: 662-675
- 2 Sagoo MK, Gnudi L. Diabetic kidney disease: an overview. Meth Mol Biol 2020; 2067: 3-7
- 3 Selby NM, Taal MW. An updated overview of diabetic nephropathy: diagnosis, prognosis, treatment goals and latest guidelines. Diabetes Obes Metab. 2020 22. 3-15
- 4 Kaur L, Garg PR, Ghosh PK. et al. Impaired homocysteine metabolism associated with high plasma interleukin-17A levels, a pro-atherogenic marker, in an endogamous population of North India. Ethnic Dis 2018; 28: 525-530
- 5 Kaplan P, Tatarkova Z, Sivonova MK. et al. Homocysteine and mitochondria in cardiovascular and cerebrovascular systems. Int J Mol Sci 2020; 21: 7698
- 6 Zhao W, Gao F, Lv L. et al. The interaction of hypertension and homocysteine increases the risk of mortality among middle-aged and older population in the United States. J Hypertens 2022; 40: 254-263
- 7 Muzurović E, Kraljević I, Solak M. et al. Homocysteine and diabetes: role in macrovascular and microvascular complications. J Diabetes Complicat 2021; 35: 107834
- 8 Cheng Y, Jin Y, Unverzagt FW. et al. The relationship between cholesterol and cognitive function is homocysteine-dependent. Clin Interv Aging 2014; 9: 1823-1829
- 9 Zhang SF, Li LZ, Zhang W. et al. Association between plasma homocysteine levels and subclinical hypothyroidism in adult subjects: a meta-analysis. Horm Metab Res 2020; 52: 625-638
- 10 Ma SC, Hao YJ, Jiao Y. et al. Homocysteine‑induced oxidative stress through TLR4/NF‑κB/DNMT1‑mediated LOX‑1 DNA methylation in endothelial cells. Mol Med Rep 2017; 16: 9181-9988
- 11 Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 2003; 26: 137-146
- 12 Chen X, Shi C, Wang Y. et al. The mechanisms of glycolipid metabolism disorder on vascular injury in type 2 diabetes. Front Physiol 2022; 13: 952445
- 13 Mao S, Xiang W, Huang S. et al. Association between homocysteine status and the risk of nephropathy in type 2 diabetes mellitus. Clin Chim Acta 2014; 431: 206-210
- 14 Moher D, Liberati A, Tetzlaff J. et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg (London, England) 2010; 8: 336-341
- 15 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
- 16 Rostom A, Dube C, Cranney A. Agency for healthcare research and quality evidence reports summaries. University of Ottawa Evidence-Based Practice center. Ottawa, Canada: University of Ottawa,; 2004
- 17 Stabler SP, Estacio R, Jeffers BW. et al. Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus. Metab Clin Exp 1999; 48: 1096-1101
- 18 Emoto M, Kanda H, Shoji T. et al. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care 2001; 24: 533-537
- 19 Okumura KI, Aso Y. High plasma homocysteine concentrations are associated with plasma concentrations of thrombomodulin in patients with type 2 diabetes and link diabetic nephropathy to macroangiopathy. Metab Clin Exp 2003; 52: 1517-1522
- 20 Aso Y, Yoshida N, Okumura KI. et al. Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia. Clin Chim Acta 2004; 348: 139-145
- 21 Sandhu JS, Singh I, Aggarwal SP. et al. Plasma homocysteine and insulin in diabetic nephropathy: relationship to body mass index. Renal Failure 2004; 26: 689
- 22 Mtiraoui N, Ezzidi I, Chaieb M. et al. MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients. Diabetes Res Clin Pr 2007; 75: 99-106
- 23 Cho EH, Kim EH, Kim WG. et al. Homocysteine as a risk factor for development of microalbuminuria in type 2 diabetes. Korean Diabetes J 2010; 34: 200-206
- 24 Li J, Shi M, Zhang H. et al. Relation of homocysteine to early nephropathy in patients with type 2 diabetes. Clin Nephrol. 2012 77. 305-310
- 25 Koluman BU, Mutluay R, Derici UB. et al. Association between osteoprotegerin, fetuin-A, carotid intima media thickness, and urinary albumin excretion in type 2 diabetes. Clin Nephrol 2013; 80: 9-16
- 26 Wang H, Cui K, Xu K. et al. Association between plasma homocysteine and progression of early nephropathy in type 2 diabetic patients. Int J Clin Exp Med 2015; 8: 11174-11180
- 27 Ma L, Liu Q, Jiang Y. et al. Genetically elevated circulating homocysteine concentrations increase the risk of diabetic kidney disease in Chinese diabetic patients. J Cell Mol Med 2019; 23: 2794-2800
- 28 Ma N, Xu N, Yin D. et al. Relationship between plasma total homocysteine and the severity of renal function in Chinese patients with type 2 diabetes mellitus aged≥75 years. Medicine 2020; 99: e20737
- 29 Ding S, Yang Y, Zheng Y. et al. Diagnostic value of the combined measurement of serum HCY and NRG4 in type 2 diabetes mellitus with early complicating diabetic nephropathy. J Personal Med 2023; 13: 556
- 30 Li H, Liu C, Zhang J. et al. The association of homocysteine level with the risk of diabetic nephropathy and diabetic retinopathy in Nhanes. Acta Diabetol 2023; 60: 907-916
- 31 Cao L, Lou X, Zou Z. et al. Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats. Microvac Res 2013; 89: 146-152
- 32 Kaplan P, Tatarkova Z, Sivonova MK. et al. Homocysteine and mitochondria in cardiovascular and cerebrovascular systems. Int J Mol Sci 2020; 21: 7698
- 33 Ling L, Chen L, Zhang C. et al. High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression. Mol Med Rep 2018; 17: 5642-5651
- 34 Ding N, Xie L, Ma F. et al. miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia. Acta Biochem Biophys Sin 2022; 54: 126-136
- 35 Xie L, Ma S, Ding N. et al. Homocysteine induces podocyte apoptosis by regulating miR-1929-5p expression through c-Myc. DNMT1 and EZH2. Mol Ooncol 2021; 15: 3203-3221
- 36 Li B, Xie H, Wang X. et al. Oxidative stress mediates renal endothelial cell damage in trichloroethylene-sensitized mice. J Toxicol Sci 2019; 44: 317-326
- 37 Migliori M, Cantaluppi V, Mannari C. et al. Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury. Plos One 2015; 10: e117530