Background and Aims:
Recently, an association between IgG N-glycosylation and type 2 diabetes (T2D) was found. The effects on complications of diabetes such as ischemic heart disease (IHD) have not yet been investigated. This may provide more insight into pathophysiology and can contribute to potential biomarker development. We hypothesize that IgG N-glycan profiles are associated with IHD in T2D.

Methods:
58 IgG glycan traits were analyzed in the DiaGene Study, a T2D case-control study (cases n=1886) with prospective follow-up on complications. Models were adjusted for sex, age, hypertension, Non-HDL, HDL, Hba1C, smoking and duration of T2D. 

Results
5 IgG N-glycan profiles and 12 derived traits were significantly associated with IHD, compared to T2D cases without IHD. Monogalactosylated (GP8) and disialylated digalactosylated FA2 glycans (GP23) without bisection were negatively associated. Agalactosylated (GP6) and monogalactosylated (GP10, GP11) FA2 glycans with bisection were positively associated. Of the derived traits, core fucose in glycans without bisection were associated negatively. Fucosylation in structures with bisection were associated positively. In prospective analyses, no significant associations were found.

Conclusions:
IHD in T2D is associated with less sialylation, less galactosylation and more fucosylation of bisected IgG glycans, all reflecting a pro-inflammatory state. Interestingly, no significant associations were found between glycans at baseline and IHD during follow-up. This may imply that the pro-inflammatory state of IgG found at baseline is a consequence rather than a cause of IHD. We are currently improving our complication registrations at follow-up in order to improve power and answer this question in more detail.

03 - IGG N-GLYCAN PATTERNS ARE ASSOCIATED WITH ISCHEMIC HEART DISEASE IN TYPE 2 DIABETES