Haifeng Zhu,1,* Ziyi Zhong,2,* Gaonian Zhao,1,* Yuan Cao,1 Wei Liu,1 Yawen Guo,1 Jing Jin1 

1Rehabilitation Medicine Center, Taizhou People’s Hospital, Taizhou City, Jiangsu Province, People’s Republic of China; 2Endocrinology Department, Nanjing First Hospital, Nanjing City, Jiangsu Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jing Jin, Email try15063@163.com

Background: Asialoglycoprotein receptor 1 (ASGR1) deficiency has been implicated in enhancing liver insulin sensitivity and reducing systemic insulin resistance, thus highlighting its pivotal role in glucose metabolism. However, the association between serum soluble asialoglycoprotein receptor 1 (sASGR1) and type 2 diabetes mellitus (T2DM) remains elusive. Therefore, we conducted a study to delve into this association.
Methods: From July to October 2024, 220 newly diagnosed T2DM patients and an equal number of matched controls with normal glucose tolerance (NGT) were enrolled. Serum sASGR1 levels were quantified using ELISA, and the carotid artery and liver were assessed with ultrasound imaging.
Results: The median serum sASGR1 level was significantly higher in the T2DM group (6.58 ng/mL) compared to the NGT group (5.26 ng/mL). Notably, no significant difference in sASGR1 levels was observed between individuals with and without carotid atherosclerosis or fatty liver. In the NGT group, sASGR1 levels exhibited a positive correlation with high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Among T2DM patients, sASGR1 levels were positively associated with estimated glomerular filtration rate (eGFR), insulin resistance (as measured by HOMA-IR), triglycerides (TG), and hs-CRP, but negatively associated with creatinine (Cr). The linear regression analysis identified Cr as an independent negative factor and hs-CRP as an independent positive factor of serum sASGR1 levels. Logistic regression analysis indicated that the highest sASGR1 group had significantly higher odds of developing T2DM compared to the lowest group, even after adjusting for potential confounders. However, this significance was attenuated after further adjustment for hs-CRP. The area under the receiver operating characteristic (ROC) curve for sASGR1 was 0.610.
Conclusion: Serum sASGR1 levels are elevated in newly diagnosed T2DM patients and correlate positively with hs-CRP. However, sASGR1 demonstrates limited predictive value for the onset of T2DM. Further research is warranted to explore the potential role of sASGR1 in renal function, blood lipids, liver health, and arteriosclerosis.

Keywords: asialoglycoprotein receptor 1, type 2 diabetes mellitus, high- sensitive C-reactive protein, clinical diabetes, serum level assessment