3.1.2 Research progress of N-Glycomics in diabetic patients
Type 1 diabetes mellitus (T1DM): Bermingham et al. retrospectively
selected 818 T1DM patients with a large annual loss of glomerular
filtration rate, and analyzed the relationship between the relative
abundance of 39 serum N-glycans and diabetes-related clinical
indicators. It was found that with the increase of glycated hemoglobin
A1c (HbA1c), the relative abundance of simple diantennary N-glycan (NA2)
gradually decreased. The relative abundance of complex multi-branched,
galactosylated and sialylated N-glycans gradually increased, and the
corresponding N-glycan levels also changed significantly with the
decrease of blood glucose levels after treatment, and returned to
healthy controls[40-42]. Another study found that multi-branched
N-glycans are closely related to the occurrence of autoimmune diseases,
which may be related to the pathogenesis of T1DM[43, 44]. Rudman et
al. analyzed the serum N-glycans of 1917 children and adolescents with
T1DM from DanDiabKids (Denmark), and found that the relative abundance
of galactosylated N-glycans in serum decreased significantly, and the
proportion of bisecting N-acetyl-D-(+)-glucosamine (GlcNAc) and high
mannose structure increased significantly. A logistic regression model
was established using serum N-glycans to identify children with T1DM.
The area under the receiver operating characteristic curve (AUC) was
0.915. The model is helpful to identify high-risk individuals of T1DM at
an early stage, and then prevent the progression of T1DM through timely
intervention, which has certain clinical practical value[45, 46].
In addition, studies have found that a variety of sugar
synthesis-related genes are associated with the pathogenesis of T1DM.For
example, the fucosyltransferase 2 gene has been identified as a T1DM
pathogenic gene[47]. Different levels of gene expression lead to the
differentiation of glycan synthesis process, which is manifested as the
change of glycan structure or quantity. It can be seen that the change
of N-glycan is closely related to the occurrence of T1DM, and the
purpose of early warning or auxiliary diagnosis of T1DM can be achieved
by detecting the change of serum N-glycan profile. It is expected that
more and more in-depth research in the future can explore the potential
clinical application value of N-glycan profile in diabetes.
Type 2 diabetes mellitus (T2DM): Dotz et al. analyzed the serum N-glycan
profiles of 1583 T2DM patients and 728 healthy controls, and found that
18 N-glycans and derived traits were closely related to T2DM, among
which the change of sialylation modification was the most prominent. The
degree of overall sialic acid modification in the T2DM group was higher
than that in the control group. The double-antenna α2,6-linked sialic
acid-modified N-glycan increased, while the three-antenna α2,3-linked
sialic acid-modified N-glycan decreased.
In addition, the proportion of fucosylation and flat typing in
dual-antenna N-glycans also decreased. Keser et al. conducted a
glycomics study on a 10-year follow-up cohort (FinRisk cohort) from
Finland, and found that individuals with T2DM had a decrease in
low-branched N-glycans, an increase in multi-branched N-glycans, and an
increase in galactose and sialylated N-glycans. The overall performance
is an increase in the structural complexity of N-glycans. Similar trends
were observed in T2DM high-risk populations and populations with
elevated HbA1c, indicating that the increased complexity of N-glycans is
closely related to the development of T2DM and poor blood glucose
control[48-50].
Testa et al. found that the relative abundance of α1,6/3-linked
monogalactosylated core fucosylated double-antenna N-glycans in the T2DM
group was significantly lower than that in the healthy control group,
while digalactosylated NA2 was significantly increased. The changes of
α1,3-linked monogalactosylated core fucosylated double-antenna N-glycans
and NA2 were more significant in T2DM patients with complications. The
former was considered to be closely related to diabetic
macroangiopathy[41-43]. Similar to the results of T1DM-related
studies, the changes of N-glycans in the serum of T2DM patients are
generally characterized by increased branching and modification[51],
but the changes of NA2 are more complex[52]. The proportion of
fucosylation modification is reduced, and the proportion of modified
N-glycans such as galactose and sialic acid is also quite different. In
summary, serum N-glycans in patients with T2DM have changed to a certain
extent, and N-glycans may become biomarkers for early diagnosis of T2DM
and complications[53], but further research is still needed.