The Role of Advanced Glycation End Products Between Thyroid Function and Diabetic Nephropathy and Metabolic Disorders

Overview

Journal Sci Rep

Specialty Science

Date 2025 Feb 28

PMID 40021692

Authors

Yi Zhang

Yanlei Wang

Qingqing Kang

Yijing Chen

Liya Ai

Keyan Hu

Li Gong

Li Zhu

Zixiang Yu

Ran Chen

Jin Cui

Tian Jiang

Qiu Zhang

Affiliations

Soon will be listed here.

Abstract

Method: This study selected community health service centers which had signed medical alliance agreement with the First Affiliated Hospital of Anhui Medical University and outpatints and inpatients in Anhui province. From March 2018 to July 2022, the multi-stage cluster sampling. method was used to screen residents aged 18-90 years in the above areas. Participants' blood was collected on an empty stomach to detect TSH, blood lipids, liver and kidney function and blood glucose, in addition, AGEs levels were detected by skin autofluorescence (SAF), and urine was retained to measure the ratio of urinary microalbumin to creatinine concentration by ACR. One-way ANOVA was used to compare the differences between general data, biochemical markers, and urinary ACR, association between variables.

Result: A total of 7000 patients who participated in community health examination and inpatients and also had no history of serious mental disorders were selected. After excluding data with missing value of more than 5%, 6921 samples were finally included, and the effective rate was 94.4%. Following health risk factors (HRFs), such as body mass index (BMI), TSH, low-density lipoprotein (LDL), TyG (triglyceride glucose index), systolic blood pressure (SBP), cholesterol (TC), and uric acid (UA) were associated with a higher incidence of urine ACR. In moderation analysis, there is an significant effect among TSH, AGEs and DN, HRFs moderate also these effect.

Conclusion: The findings suggest that HRFs such as HDL, TyG and TC should be prioritized when evaluating indicators related to DN to effectively reduce DN in Chinese patients with high health risk levels. Comprehensive indicators may be an effective and practical. method to evaluate the metabolic progression of DN. Optimizing thyroid function management may be a new strategy to prevent and treat DN and may help reduce the risk of AGE-related complications in people with diabetes. This study highlights the important role of AGEs in the relationship between TSH and DN. In addition, future studies should further explore how to improve the management and prevention of DN by regulating TSH.Among the leading causes of disability and death in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes (T2DM), chronic kidney disease (CKD) occupies a certain position. Multi-factor intervention targeting advanced glycation end products (AGEs), blood glucose, blood pressure and lipids can reduce the morbidity and mortality of diabetic nephropathy (DN) in T2DM patients through thyroid stimulating hormone (TSH), which plays an important role in the pathological process of metabolic diseases such as DN. AGEs, as a key factor in metabolic regulation, may affect the formation and function of the thyroid gland; However, in DN, the correlation between AGEs and TSH has not been clarified. We hypothesized that AGEs aggravated the negative effect of TSH on DN. The.

References

Abbasi F, Reaven G . Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol. Metabolism. 2011; 60(12):1673-6. DOI: 10.1016/j.metabol.2011.04.006. View

Hata S, Ushigome E, Hosomi Y, Yoshimura T, Takegami M, Kitagawa N . Impact of continued high blood pressure on the progression of diabetic nephropathy after 10 years: KAMOGAWA-HBP study. Hypertens Res. 2023; 46(3):565-574. DOI: 10.1038/s41440-022-01136-3. View

Xu W, Zhou Y, Jiang Q, Fang Y, Yang Q . Risk prediction models for diabetic nephropathy among type 2 diabetes patients in China: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024; 15:1407348. PMC: 11251916. DOI: 10.3389/fendo.2024.1407348. View

Shen Y, Cai R, Sun J, Dong X, Huang R, Tian S . Diabetes mellitus as a risk factor for incident chronic kidney disease and end-stage renal disease in women compared with men: a systematic review and meta-analysis. Endocrine. 2016; 55(1):66-76. DOI: 10.1007/s12020-016-1014-6. View

Maric C, Hall J . Obesity, metabolic syndrome and diabetic nephropathy. Contrib Nephrol. 2011; 170:28-35. PMC: 3177237. DOI: 10.1159/000324941. View

Hayes A, Rockwood N . Regression-based statistical mediation and moderation analysis in clinical research: Observations, recommendations, and implementation. Behav Res Ther. 2016; 98:39-57. DOI: 10.1016/j.brat.2016.11.001. View

Lavecchia A, Mantzouratou P, Cerullo D, Locatelli M, Conti S, Tironi M . Thyroid hormone treatment counteracts cellular phenotypical remodeling in diabetic organs. iScience. 2023; 26(10):107826. PMC: 10518716. DOI: 10.1016/j.isci.2023.107826. View

Ellervik C, Mora S, Ridker P, Chasman D . Hypothyroidism and Kidney Function: A Mendelian Randomization Study. Thyroid. 2020; 30(3):365-379. PMC: 7074918. DOI: 10.1089/thy.2019.0167. View

DAdamo E, De Leonibus C, Giannini C, Corazzini V, de Remigis A, Chiarelli F . Thyroid dysfunction in obese pre-pubertal children: oxidative stress as a potential pathogenetic mechanism. Free Radic Res. 2012; 46(3):303-9. DOI: 10.3109/10715762.2011.653967. View

10.

Fei X, Xing M, Wo M, Wang H, Yuan W, Huang Q . Thyroid stimulating hormone and free triiodothyronine are valuable predictors for diabetic nephropathy in patient with type 2 diabetes mellitus. Ann Transl Med. 2018; 6(15):305. PMC: 6123216. DOI: 10.21037/atm.2018.07.07. View

11.

Rosario R, Prabhakar S . Lipids and diabetic nephropathy. Curr Diab Rep. 2006; 6(6):455-62. DOI: 10.1007/s11892-006-0079-7. View

12.

Cui C, Liu L, Qi Y, Han N, Xu H, Wang Z . Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: a national cohort study. Cardiovasc Diabetol. 2024; 23(1):156. PMC: 11077847. DOI: 10.1186/s12933-024-02244-9. View

13.

Gao J, Liu J . Correlation of serum thyrotropin and thyroid hormone levels with diabetic kidney disease: a cross-sectional study. BMC Endocr Disord. 2024; 24(1):170. PMC: 11363369. DOI: 10.1186/s12902-024-01699-x. View

14.

Liu H, Yao X, Wang L, Liu J, Li X, Fu X . The causal relationship between 5 serum lipid parameters and diabetic nephropathy: a Mendelian randomization study. Front Endocrinol (Lausanne). 2024; 15:1358358. PMC: 11165179. DOI: 10.3389/fendo.2024.1358358. View

15.

Zhang Y, Jiang T, Liu C, Hu H, Dai F, Xia L . Effectiveness of Early Advanced Glycation End Product Accumulation Testing in the Diagnosis of Diabetes: A Health Risk Factor Analysis Using the Body Mass Index as a Moderator. Front Endocrinol (Lausanne). 2022; 12:766778. PMC: 8967381. DOI: 10.3389/fendo.2021.766778. View

16.

Bjornstad P, Lanaspa M, Ishimoto T, Kosugi T, Kume S, Jalal D . Fructose and uric acid in diabetic nephropathy. Diabetologia. 2015; 58(9):1993-2002. PMC: 4826347. DOI: 10.1007/s00125-015-3650-4. View

17.

Van Buren P, Toto R . Hypertension in diabetic nephropathy: epidemiology, mechanisms, and management. Adv Chronic Kidney Dis. 2011; 18(1):28-41. PMC: 3221014. DOI: 10.1053/j.ackd.2010.10.003. View

18.

Sun Y, Teng D, Zhao L, Shi X, Li Y, Shan Z . Impaired Sensitivity to Thyroid Hormones Is Associated with Hyperuricemia, Obesity, and Cardiovascular Disease Risk in Subjects with Subclinical Hypothyroidism. Thyroid. 2022; 32(4):376-384. DOI: 10.1089/thy.2021.0500. View

19.

Sourris K, Ding Y, Maxwell S, Al-Sharea A, Kantharidis P, Mohan M . Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation. Kidney Int. 2023; 105(1):132-149. DOI: 10.1016/j.kint.2023.09.029. View

20.

Boruah P, Baruah A, Barman B, Nath C, Hajong R, Naku N . A Study to Evaluate the Association Between Thyroid Function and Serum Potassium Level in Diagnosed Cases of Diabetic Nephropathy. Cureus. 2021; 13(10):e18569. PMC: 8575322. DOI: 10.7759/cureus.18569. View