Abstract

Background The relationship between the IgG glycan panel and type 2 diabetes remains unclear in Chinese population. We aimed to investigate the association of the IgG glycan profile and glycan score with type 2 diabetes. Methods In the discovery population, 162 individuals diagnosed with type 2 diabetes and 162 matched controls from Beijing health management cohort were included. We analyzed the IgG glycan profile and composed a glycan score for type 2 diabetes. Findings were validated in the replication population from Beijing Xuanwu community cohort (280 cases and 508 controls). Area under curve (AUC) using 10-fold and bootstrap validation, net reclassification index (NRI), and integrated discrimination index (IDI) were calculated for the glycan score. Results In the discovery population, 5 initial IgG glycans and 7 derived traits were significantly associated with type 2 diabetes after Bonferroni correction and Lasso selection, which were validated in the replication population subsequently. The glycan score composed of these IgG glycans and traits showed a strong association with type 2 diabetes (combined odds ratio (OR): 3.78) and its risk factors. In the replication population, AUC of the model involving clinical traits improved from 0.74 to above 0.90, and the values of NRI and IDI were 0.35 and 0.42, respectively, with the glycan score added. Conclusions IgG glycosylation profiles were associated with type 2 diabetes and the glycan score may be a novel indicator for diabetes which reflected a proinflammatory status.

Highlights

  • The relationship between the IgG glycan panel and type 2 diabetes remains unclear in Chinese population

  • We described the association of the IgG glycan profile and glycan score with type 2 diabetes in Chinese population

  • We found and replicated that GP3, GP5, GP20, GP22, GP24, and several IgG-derived traits could compose a glycan score to discriminate the type 2 diabetes individuals from the health controls effectively for the first time

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Summary

Introduction

The relationship between the IgG glycan panel and type 2 diabetes remains unclear in Chinese population. We aimed to investigate the association of the IgG glycan profile and glycan score with type 2 diabetes. We analyzed the IgG glycan profile and composed a glycan score for type 2 diabetes. 5 initial IgG glycans and 7 derived traits were significantly associated with type 2 diabetes after Bonferroni correction and Lasso selection, which were validated in the replication population subsequently. The glycan score composed of these IgG glycans and traits showed a strong association with type 2 diabetes (combined odds ratio (OR): 3.78) and its risk factors. AUC of the model involving clinical traits improved from 0.74 to above 0.90, and the values of NRI and IDI were 0.35 and 0.42, respectively, with the glycan score added. The attached glycans regulate the stability of IgG and its effector functions [6], involving antibody-dependent cell-mediated cytotoxicity (ADCC) [7]

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