(P30-035-23) The Causal Effects of N-Glycosylation of Immunoglobulin G on Type 2 Diabetes Mellitus and Glycemic Control

Objectives: N-glycomic changes of immunoglobulin G (IgG) have been associated with many chronic diseases. However, it remains unclear whether type 2 diabetes (T2D) is driven by the alterations of IgG N-glycosylation. By using Mendelian randomization methods, we examined the causal effects of all IgG N-glycans (IGPs) on T2D and glycemic traits.

Methods: Briefly, univariable and multivariable MR analyses were conducted for causal determination.

Results: Our univariable MR analyses identified IGP8 and IGP31 negatively associated with T2D risk and IGP26 positively associated with T2D risk. The IGP association pattern of T2D showed strong similarity to those of corrected insulin response (CIR), area under the curve for insulin over a total area under the curve for glucose (AUCI/AUCG), homeostasis model assessment estimates of β-cell function (HOMA-B), and glycated hemoglobin (HbA1c). When focused on the directly measured IGPs, our multivariable MR analyses identified IGP3 and IGP13 positively associated with T2D risk, and non-linear MR-BMA analysis prioritized IGP17 as the best model for T2D risk.

Conclusions: Our study provide clear genetic evidence supporting a causal link between IgG N-glycosylation and T2D, which sheds light on further developing novel interventions for the prevention of diabetes.

Funding Sources: This study was supported by research grants from the National Natural Science Foundation of China.