engleski

N-GLYCOSYLATION OF TOTAL SERUM PROTEINS IN ADULTS WITH TYPE I DIABETES MELLITUS

Aberrant plasma protein N-glycosylation has been reported in children newly diagnosed with type 1 diabetes (T1D) and N-glycosylation has also been associated with poor glycaemic control and nephropathy in T1D. N-glycosylation features distinct for adult patients with T1D, however, remain to be assessed. In this study we compared the serum protein N-glycosylation between adult patients and corresponding healthy controls as well as examined the association of N- glycans with common diabetic complications, duration of the disease, glycaemic control, and smoking. Serum N-glycans were analysed by UPLC in 201 patients with T1D (18-70) and 298 healthy controls (18-79). N-glycome was divided into 39 glycan groups and 16 derived traits calculated based on structural similarities. Serum N-glycome in T1D subjects exhibited significant decrease in monogalactosylated and an increase in digalactosylated, monosialylated and antennary fucosylated structures, as well as changes in 19 directly measured N- glycan traits. None of the N-glycosylation features, however, correlated with the duration of the disease nor with the development or progression of microvascular complications, similarly to glycaemic parameters, excluding HbA1c. HbA1c was positively associated with sialylated and highly branched glycans, while the effect of smoking was observed through increased complexity of plasma N-glycome.This study shows that T1D associates with a multitude of changes in the N-glycome, reflecting the complexity of the disease. Some of the changes were previously described in newly diagnosed children, but a number of new are found to be present only in the adult patients: e.g., an increase in antennary-fucosylated structures commonly originating from alpha-1-acid glycoprotein, or a decrease in oligomannose structures associated with immunoglobulin M. Interestingly, glycans did not associate with the duration of the disease or with microvascular complications, while conversely poor glycaemic control and smoking were strongly reflected in the N-glycome. In general, this study provides a more comprehensive portrayal of N-glycan changes in adult patients with T1D and highlights changes in certain plasma proteins, but nevertheless warrants further research on N-glycosylation in T1D.

Type 1 diabetes mellitus, N-glycosylation, Serum protein N-glycosylation

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