Elevated Circulating Homocysteine Concentrations Delayed Nerve Conduction Velocity and Increase the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2024 Dec 26

PMID 39722814

Authors

Nannan Lv

Luzhu Jia

Fei Liu

Lan Cheng

Feng Liu

Jinsong Kuang

Xin Chen

Affiliations

Soon will be listed here.

Abstract

Introduction: China has the largest population of individuals with diabetes, and the prevalence of various complications among patients with type 2 diabetes remains high. Diabetic nephropathy affects approximately 20% to 40% of diabetic patients, becoming a major cause of chronic kidney disease and end-stage renal disease. Furthermore, around 50% of patients develop diabetic peripheral neuropathy (DPN), which is closely associated with physical disability, increased healthcare costs, and reduced work productivity. There is an urgent need for novel strategies in prevention, diagnosis, and treatment to improve patient outcomes.

Methods: In this study, 163 patients with type 2 diabetes were selected as the observation group and further divided into three subgroups based on homocysteine (HCY) levels. The study measured several clinical parameters, including homocysteine, blood glucose, blood lipids, glycated hemoglobin, urinary microalbumin, urinary albumin-to-creatinine ratio (ACR), electromyography, and highly-sensitive C-reactive protein (CRP), among others. The levels of these indicators were analyzed and compared across the subgroups.

Results: The results revealed significant differences in uric acid, creatinine, urinary microalbumin, urinary ACR, and nerve conduction velocity (right tibial nerve sensory conduction) among different HCY levels in patients with type 2 diabetes (P < 0.05). Linear regression analysis indicated that homocysteine levels were associated with systolic blood pressure, glycated hemoglobin, fasting C-peptide, uric acid, creatinine, urinary microalbumin, and nerve conduction velocity (including motor conduction velocity of the ulnar nerve and sensory conduction velocity of the sural nerve).

Discussion: The clinical assessment of homocysteine in diabetic patients holds significant importance in the prevention of microvascular complications. Lowering HCY levels may offer a promising therapeutic approach for managing microvascular disease in diabetes.

References

Hermann A, Sitdikova G . Homocysteine: Biochemistry, Molecular Biology and Role in Disease. Biomolecules. 2021; 11(5). PMC: 8156138. DOI: 10.3390/biom11050737. View

Li Y, Teng D, Shi X, Qin G, Qin Y, Quan H . Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ. 2020; 369:m997. PMC: 7186854. DOI: 10.1136/bmj.m997. View

Dong Y, Fernandes C, Liu Y, Wu Y, Wu H, Brophy M . Role of endoplasmic reticulum stress signalling in diabetic endothelial dysfunction and atherosclerosis. Diab Vasc Dis Res. 2016; 14(1):14-23. PMC: 5161113. DOI: 10.1177/1479164116666762. View

Duan J, Wang C, Liu D, Qiao Y, Pan S, Jiang D . Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in Chinese rural residents: a cross-sectional survey. Sci Rep. 2019; 9(1):10408. PMC: 6639314. DOI: 10.1038/s41598-019-46857-7. View

Majumder A . Targeting Homocysteine and Hydrogen Sulfide Balance as Future Therapeutics in Cancer Treatment. Antioxidants (Basel). 2023; 12(8). PMC: 10451792. DOI: 10.3390/antiox12081520. View

Go A, Yang J, Tan T, Cabrera C, Stefansson B, Greasley P . Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus. BMC Nephrol. 2018; 19(1):146. PMC: 6014002. DOI: 10.1186/s12882-018-0942-1. View

Geng T, Zhu K, Lu Q, Wan Z, Chen X, Liu L . Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study. PLoS Med. 2023; 20(1):e1004135. PMC: 9831321. DOI: 10.1371/journal.pmed.1004135. View

Crasto W, Patel V, Davies M, Khunti K . Prevention of Microvascular Complications of Diabetes. Endocrinol Metab Clin North Am. 2021; 50(3):431-455. DOI: 10.1016/j.ecl.2021.05.005. View

Jiang G, Luk A, Tam C, Xie F, Carstensen B, Lau E . Progression of diabetic kidney disease and trajectory of kidney function decline in Chinese patients with Type 2 diabetes. Kidney Int. 2018; 95(1):178-187. DOI: 10.1016/j.kint.2018.08.026. View

10.

Hasan T, Arora R, Bansal A, Bhattacharya R, Sharma G, Singh L . Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med. 2019; 51(2):1-13. PMC: 6389897. DOI: 10.1038/s12276-019-0216-4. View

11.

Wang D, Zhai J, Liu D . Serum folate, vitamin B12 levels and diabetic peripheral neuropathy in type 2 diabetes: A meta-analysis. Mol Cell Endocrinol. 2017; 443:72-79. DOI: 10.1016/j.mce.2017.01.006. View

12.

Vinik A . Management of neuropathy and foot problems in diabetic patients. Clin Cornerstone. 2003; 5(2):38-55. DOI: 10.1016/s1098-3597(03)90017-2. View

13.

Liu G, Hirtz M, Fuchs H, Zheng Z . Development of Dip-Pen Nanolithography (DPN) and Its Derivatives. Small. 2019; 15(21):e1900564. DOI: 10.1002/smll.201900564. View

14.

Zhao J, Li Y, Xin L, Sun M, Yu C, Shi G . Clinical Features and Rules of Chinese Herbal Medicine in Diabetic Peripheral Neuropathy Patients. Evid Based Complement Alternat Med. 2020; 2020:5795264. PMC: 7382735. DOI: 10.1155/2020/5795264. View

15.

Selvarajah D, Kar D, Khunti K, Davies M, Scott A, Walker J . Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention. Lancet Diabetes Endocrinol. 2019; 7(12):938-948. DOI: 10.1016/S2213-8587(19)30081-6. View

16.

Zhou L . Homocysteine and Parkinson's disease. CNS Neurosci Ther. 2023; 30(2):e14420. PMC: 10848096. DOI: 10.1111/cns.14420. View

17.

. Diabetic neuropathy. Nat Rev Dis Primers. 2019; 5(1):42. PMC: 7096070. DOI: 10.1038/s41572-019-0097-9. View

18.

Ma L, Liu Q, Jiang Y, Zhao H, Zhao T, Cao Y . Genetically elevated circulating homocysteine concentrations increase the risk of diabetic kidney disease in Chinese diabetic patients. J Cell Mol Med. 2019; 23(4):2794-2800. PMC: 6433716. DOI: 10.1111/jcmm.14187. View

19.

Zheng L, Zhang H, Guan Z, Hu M, Zhang T, Ge S . Elevated serum homocysteine level in the development of diabetic peripheral neuropathy. Genet Mol Res. 2015; 14(4):15365-75. DOI: 10.4238/2015.November.30.14. View

20.

Ma N, Xu N, Yin D, Liu W, Wu M, Cheng X . Relationship between plasma total homocysteine and the severity of renal function in Chinese patients with type 2 diabetes mellitus aged ≥75 years. Medicine (Baltimore). 2020; 99(27):e20737. PMC: 7337561. DOI: 10.1097/MD.0000000000020737. View