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Birukov, Anna; Plavša, Branimir; Eichelmann, Fabian; Kuxhaus, Olga; Hoshi, Rosangela Akemi; Rudman, Najda; Štambuk, Tamara; Trbojević-Akmačić, Irena; Schiborn, Catarina; Morze, Jakub; Mihelčić, Matea; Cindrić, Ana; Liu, Yanyan; Demler, Olga; Perola, Markus; Mora, Samia; Schulze, Matthias B; Lauc, Gordan; Wittenbecher, Clemens
Diabetes care, 11/2022, Letnik: 45, Številka: 11Journal Article
N-glycosylation is a functional posttranslational modification of immunoglobulins (Igs). We hypothesized that specific IgG N-glycans are associated with incident type 2 diabetes and cardiovascular disease (CVD). We performed case-cohort studies within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (2,127 in the type 2 diabetes subcohort 741 incident cases; 2,175 in the CVD subcohort 417 myocardial infarction and stroke cases). Relative abundances of 24 IgG N-glycan peaks (IgG-GPs) were measured by ultraperformance liquid chromatography, and eight glycosylation traits were derived based on structural similarity. End point-associated IgG-GPs were preselected with fractional polynomials, and prospective associations were estimated in confounder-adjusted Cox models. Diabetes risk associations were validated in three independent studies. After adjustment for confounders and multiple testing correction, IgG-GP7, IgG-GP8, IgG-GP9, IgG-GP11, and IgG-GP19 were associated with type 2 diabetes risk. A score based on these IgG-GPs was associated with a higher diabetes risk in EPIC-Potsdam and independent validation studies (843 total cases, 3,149 total non-cases, pooled estimate per SD increase 1.50 95% CI 1.37-1.64). Associations of IgG-GPs with CVD risk differed between men and women. In women, IgG-GP9 was inversely associated with CVD risk (hazard ratio HR per SD 0.80 95% CI 0.65-0.98). In men, a weighted score based on IgG-GP19 and IgG-GP23 was associated with higher CVD risk (HR per SD 1.47 95% CI 1.20-1.80). In addition, several derived traits were associated with cardiometabolic disease incidence. Selected IgG N-glycans are associated with cardiometabolic risk beyond classic risk factors, including clinical biomarkers.
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