Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (9): 102-107.doi: 10.6040/j.issn.1671-7554.0.2025.0087

• Clinical Research • Previous Articles    

Correlation between the levels of serum Isthmin1, Gremlin2 and retinopathy in type 2 diabetic patients

MENG Xiaomei, HAO Yaping, WANG Liang, YU Xiao, TANG Yuxiao   

  1. Department of Endocrinology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, China
  • Published:2025-09-08

PDF (PC)

36

Abstract: Objective To investigate the correlation between the levels of serum Isthmin1(ISM1), Gremlin2(GREM2)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM). Methods A total of 148 patients with T2DM who were treated in the Affiliated Yantai Yuhuangding Hospital of Qingdao University from January 1,2023 to December 31,2023 were included in the study and divided into a non-DR(NDR)group(n=81)and a DR group(n=67)based on the absence or presence of DR. Serum ISM1 and GREM2 levels were measured by enzyme-linked immunosorbent assay. Results Significant differences in diabetic duration, the presence of hypertension, systolic blood pressure(SBP), interleukin 6, urinary albumin-to-creatinine ratio(UACR)and carotid intima-media thickness(cIMT)were observed between the NDR and DR groups(all P<0.05). Compared with the NDR group, DR group had higher levels of ISM1 ［2.63±0.99 vs. 1.24±0.72 ng/mL］ and GREM2 ［1 001.01(920.00,1 149.71), vs. 896.51(771.02,997.45)pg/mL］(all P<0.001). After adjustments for age and gender, partial correlation analysis revealed that the presence of DR was positively correlated with SBP, triglycerides, UACR, cIMT, ISM1 and GREM2(all P<0.05). Multivariate Logistic regression analysis showed that ISM1, GREM2, SBP and UACR were independent influencing factors of DR in patients with T2DM(all P<0.05). Conclusion The risk of DR in T2DM patients increases with the elevation of ISM1 and GREM2, and early screening for DR may be facilitated by detecting their levels in serum.

Key words: Isthmin1, Gremlin2, Diabetic retinopathy, Type 2 diabetes mellitus

CLC Number: 

  • R587.1
[1] 郑凤杰, 宋玉文, 孙爱丽, 等. 糖尿病周围神经病变与肌少症的关联性[J]. 山东大学学报(医学版), 2021, 59(6): 38-44. ZHENG Fengjie, SONG Yuwen, SUN Aili, et al. Correlation betw een diabetic peripheral neuropathy and sarcopenia[J]. Journal of Shandong University(Health Sciences), 2021, 59(6): 38-44.
[2] 中华医学会眼科学分会眼底病学组, 中国医师协会眼科医师分会眼底病学组, 许迅, 等. 我国糖尿病视网膜病变临床诊疗指南(2022年): 基于循证医学修订[J]. 中华眼底病杂志, 2023(2): 99-124.
[3] Wang C, Xu MY, Feng RY, et al. Serum isthmin-1 levels are positively and independently correlated with albuminuria in patients with type 2 diabetes mellitus[J]. BMJ Open Diabetes Res Care, 2022, 10(5): e002972. doi: 10.1136/bmjdrc-2022-002972
[4] Gustafson B, Hammarstedt A, Hedjazifar S, et al. BMP4 and BMP antagonists regulate human white and beige adipogenesis[J]. Diabetes, 2015, 64(5): 1670-1681.
[5] Qin D, Jiang YR, Meng ZJ. Gremlin in the vitreous of patients with proliferative diabetic retinopathy and the downregulation of gremlin in retinal pigment epithelial cells[J]. J Diabetes Res, 2020, 2020: 9238742. doi: 10.1155/2020/9238742
[6] Lavoz C, Alique M, Rodrigues-Diez R, et al. Gremlin regulates renal inflammation via the vascular endothelial growth factor receptor 2 pathway[J]. J Pathol, 2015, 236(4): 407-420.
[7] Nolan K, Thompson TB. The DAN family: modulators of TGF-β signaling and beyond[J]. Protein Sci, 2014, 23(8): 999-1012.
[8] 中华医学会糖尿病学分会, 朱大龙. 中国2型糖尿病防治指南(2020年版)[J]. 中华糖尿病杂志, 2021, 13(4): 315-409.
[9] 姚馨悦, 肖燕, 高珊, 等. 均衡营养素膳食联合二甲双胍治疗对多囊卵巢综合征患者糖脂代谢影响的研究[J]. 中华糖尿病杂志, 2024, 16(7): 762-769. YAO Xinyue, XIAO Yan, GAO Shan, et al. Effects of a balanced nutrient diet combined with metformin on glucose and lipid metabolism in patients with polycystic ovary syndrome[J]. Chinese Journal of Diabetes Mellitus, 2024, 16(7): 762-769.
[10] 刘岩, 杨路路, 丁蕊娜, 等. 三种肾小球滤过率评估方程在正常人群中的应用[J]. 国际泌尿系统杂志, 2023, 43(1): 154-158. LIU Yan, YANG Lulu, DING Ruina, et al. Three kinds of glomerular filtration rate evaluation equation in the application of the general population[J]. International Journal of Urology and Nephrology, 2023, 43(1): 154-158.
[11] Jin GM, Xiao W, Ding XH, et al. Prevalence of and risk factors for diabetic retinopathy in a rural Chinese population: the Yangxi eye study[J]. Invest Ophthalmol Vis Sci, 2018, 59(12): 5067-5073.
[12] Xu J, Li M, Jiang XL, et al. Omentin-1 and diabetes: more evidence but far from enough[J]. Arch Physiol Biochem, 2024, 130(6): 599-605.
[13] Yasir M, Senthilkumar GP, Jayashree K, et al. Association of serum omentin-1, apelin and chemerin concentrations with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients[J]. Arch Physiol Biochem, 2022, 128(2): 313-320.
[14] Jiang ZW, Zhao M, Voilquin L, et al. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis[J]. Cell Metab, 2021, 33(9): 1836-1852.e11.
[15] 冯瑞颖. 2型糖尿病患者血清Ism-1与胰岛β-细胞功能、胰岛素抵抗以及糖尿病视网膜病变的相关性研究[D]. 济南: 山东大学, 2024. FENG Ruiying. The correlation between serum Ism-l and Pancreatic β-cell function, Insulin resistance, and Diabetic retinopathy in patients with Type 2 Diabetes[D]. Jinan: Shandong University, 2024.
[16] Kane R, Stevenson L, Godson C, et al. Gremlin gene expression in bovine retinal pericytes exposed to elevated glucose[J]. Br J Ophthalmol, 2005, 89(12): 1638-1642.
[17] Du XF, Huang K, Chen XY, et al. Gremlin-1 promotes IL-1β-stimulated chondrocyte inflammation and extracellular matrix degradation via activation of the MAPK signaling pathway[J]. J Biochem Mol Toxicol, 2023, 37(9): e23404. doi: 10.1002/jbt.23404
[18] Wang XB, Zhu H, Song W, et al. Gremlin regulates podocyte apoptosis via transforming growth factor-β(TGF-β)pathway in diabetic nephropathy[J]. Med Sci Monit, 2018, 9(24): 183-189.
[19] Liu Y, Chen ZJ, Cheng HX, et al. Gremlin promotes retinal pigmentation epithelial(RPE)cell proliferation, migration and VEGF production via activating VEGFR2-Akt-mTORC2 signaling[J]. Oncotarget, 2017, 8(1): 979-987.
[20] Brownlee M. Biochemistry and molecular cell biology of diabetic complications[J]. Nature, 2001, 414(6865): 813-820.
[21] Gupta N, Mansoor S, Sharma A, et al. Diabetic retino-pathy and VEGF[J]. Open Ophthalmol J, 2013, 7(1): 4-10.
[22] Wu XJ, Qin B, Cheng RW, et al. Angiogenic and fibrogenic dual-effect of Gremlin1 on proliferative diabetic retinopathy[J]. Int J Biol Sci, 2024, 20(3): 897-915.
[23] Xu MY, Feng RY, Feng RQ, et al. Glomerular filtration rate in patients with type 2 diabetes mellitus: is serum isthmin-1 level a possible link?[J]. BMJ Open Diabetes Res Care, 2023, 11(4): e003402. doi: 10.1136/bmjdrc-2023-003402
[24] Venugopal S, Chen M, Liao WP, et al. Isthmin is a novel vascular permeability inducer that functions through cell-surface GRP78-mediated Src activation[J]. Cardiovasc Res, 2015, 107(1): 131-142.
[25] 付俊玲, 穆志静, 孙丽娜, 等. 住院2型糖尿病患者视网膜病变的危险因素及胆红素水平分析[J]. 中华糖尿病杂志, 2022, 14(9): 947-953. FU Junling, MU Zhijing, SUN Lina, et al. Analysis of risk factors and bilirubin levels of diabetic retinopathy in hospitalized patients with type 2 diabetes mellitus[J]. Chinese Journal of Diabetes Mellitus, 2022, 14(9): 947-953.
[26] 陈雪, 赵松青, 陆卫平, 等. 尿白蛋白/肌酐比值对2型糖尿病视网膜病变的影响及其截断值的判定[J]. 中华内分泌代谢杂志, 2022, 38(12): 1046-1051. CHEN Xue, ZHAO Songqing, LU Weiping, et al. Effect of urinary albumin/creatinine ratio on type 2 diabetic retinopathy and its cut-off value for early diabetic retinopathy diagnosis[J]. Chinese Journal of Endocrino-logy and Metabolism, 2022, 38(12): 1046-1051.
[27] Li YT, Wang Y, Hu XJ, et al. Association between systolic blood pressure and diabetic retinopathy in both hypertensive and normotensive patients with type 2 diabetes: risk factors and healthcare implications[J]. Healthcare(Basel), 2021, 9(5): 580. doi: 10.3390/healthcare9050580
[1] SHEN Lujia, LU Tianwei, GONG Weiming, ZHAO Yansong, WANG Shukang, YUAN Zhongshang. Application of metabolomic risk score in predicting cardiovascular outcomes in patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2025, 63(8): 69-78.
[2] CHEN Yingying, WANG Lu, HU Xifeng, ZHU Gaopei, XUE Fuzhong. A Bayesian network-based risk prediction study of stroke in patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2025, 63(8): 94-102.
[3] LI Jinquan, GAO Meifang, YAN Fei, DONG Ming. Frequency and risk factors of muscle cramp in 136 cases of type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 20-24.
[4] HAN Mei, MENG Weijing, TAO Zikun, YANG Xi, XU Yaqi, MU Huaxia, BU Weixiao, WANG Suzhen, SHI Fuyan. Causal mediation analysis with multiple-mediator of hypertension and depression between type 2 diabetes mellitus and cognitive function based on G-computation [J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 101-108.
[5] LYU Li, JIANG Lu, CHEN Shihong, ZHUANG Xianghua, SONG Yuwen, WANG Dianhui, AN Wenjuan, LI Qian, PAN Zhe. Related factors of osteoporosis in 210 postmenopausal women with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 19-25.
[6] LIU Ping, SONG Yuwen, WANG Ping, TIAN Guangwei, ZHENG Fengjie, LYU Li, DU Jiaojiao, ZHANG Jing, ZHUANG Xianghua, CHEN Shihong. Correlation between vitamin D deficiency and depression in patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 51-56.
[7] ZHENG Fengjie, SONG Yuwen, SUN Aili, PAN Zhe, WANG Dianhui, LOU Nengjun, LYU Li, ZHUANG Xianghua, CHEN Shihong. Correlation between diabetic peripheral neuropathy and sarcopenia [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 38-44.
[8] WANG Yuyu, GAO Li, CHEN Shaohua. Association between cognitive impairment and thyroid function after acute ischemic stroke in 94 patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 56-61.
[9] TANG Bo, SHAO Jing, CUI Jing, SUN Jianping. A mechanism study on the association of type 2 diabetes and high-density lipoprotein [J]. Journal of Shandong University (Health Sciences), 2020, 58(3): 99-106.
[10] JIN Haiyan, ZHANG Yan, MA Xiaoli, HAN Yu, ZHAO Huichen, LIU Yuantao, ZHANG Yuchao. Expressions of miR-122 and miR-33a in patients with type 2 diabetes complicated with coronary artery disease [J]. Journal of Shandong University (Health Sciences), 2020, 58(3): 94-98.
[11] TIAN Zhongyan, LI Yuqian, LIU Xiaotian, SHI Yuanyuan, ZHANG Haiqing, ZHANG Xia, QIAN Xinling, YIN Lei, ZHAO Jingzhi, WANG Chongjian. Relationship between PSMD6 gene rs831571 locus polymorphism and the susceptibility of T2DM: a case-control study [J]. Journal of Shandong University (Health Sciences), 2018, 56(7): 51-56.
[12] CHEN Pan, JIANG Chunxia, LEI Yi. Correlation between peripheral Syntaxin 8 expression and chronic inflammation and glucose-lipid metabolism in type 2 diabetes mellitus patients [J]. Journal of Shandong University (Health Sciences), 2018, 56(12): 26-32.
[13] LI Shuai, WANG Yalin, SUN Zhongwen, ZHU Meijia. Expression changes and mechanism of Nod-like receptor protein 3 inflammasome in the cerebral microvascular endothelial cells in type 2 diabetes mellitus [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(3): 6-11.
[14] PENG Li, QIANG Ye, ZHAO Huichen, CHEN Shihong, YAO Weidong, LIU Yuantao. Clinical studies on type 2 diabetic patients treated with sitagliptin [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(8): 60-63.
[15] LIN Dong, GUAN Qingbo. Association of serum testosterone level and non-alcoholic fatty liver disease in male patients with T2DM [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(7): 33-37.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd