Erythrocyte-bound apolipoprotein B in diabetes mellitus

Cardiovascular disease (CVD) is a major global health burden and, to date,
still the number one cause of death globally [1]. The majority of CVD is caused
by atherosclerosis, which is the result of a combination of lipid accumulation
and a chronic inflammatory situation resulting in the formation of arterial
plaques [2,3].
Lipids play a key role in atherogenesis, the first step being the invasion of
the vessel wall by lipid particles [4]. Lipids are transported within
lipoproteins. All atherogenic lipoproteins carry apolipoprotein B (apo B) as
their structural protein [5]. Increased concentrations of apo B are associated
with CVD [6-8]. These apolipoproteins have become standard clinical laboratory
measurements. It has been shown previously that apo B can also bind to blood
cells such as leukocytes and erythrocytes [9,10].
Recently, our group found evidence that erythrocyte-bound apo B (ery-apo B) is
inversely associated with CVD, and that it is unrelated from serum levels of
apo B [11]. These studies were performed in patients with and without a history
of CVD. Data in other specific groups of patients are lacking.
It remains unclear which determinants are involved in ery-apo B levels in
individual patients. We postulated previously that the transport of
lipoproteins by ery-apo B is due to binding of apo B containing lipoproteins
with complement receptor 1 (CR1) on erythrocytes after complement activation on
the surface of these lipoproteins [12]. Around 30% of the variation in ery-apo
B can be explained by blood group type O and CR1 expression polymorphism
[11,13], but other factors are still unclear.

Diabetes mellitus type 1 and type 2 are strongly associated with
atherosclerosis, in the case of type T2DM patients have a two-fold increased
risk of cardiovascular disease, patients with T1DM have an 2-4 fold increased
risk of cardiovascular disease [14]. Many studies have shown that chronic
inflammation is closely linked to atherosclerosis [15-17], and the increased
risk in patients with diabetes is due to this chronic inflammation [18,19]. The
development of cardiovascular disease within patients with DM differs greatly,
one explanation for this difference in cardiovascular risk might the level of
ery-apo B.

In this exploratory study we aim to explore the values of apolipoprotein B
bound to erythrocytes in patients with diabetes mellitus type 1 or 2, to
evaluate the relationship with clinical and subclinical atherosclerosis and to
compare these results with controls without diabetes.
Furthermore, we want to investigate if there are other factors associated with
the levels of blood cell bound apo B, especially factors associated with
complement activation.

The study will be a cross-sectional study.

No intervention will take place. Volunteers will visit the outpatient clinic
one or two times (depending on availability of a recent IMT measurement). A
maximum of 30ml (depending on availability of recent blood results) blood will
be drawn. Besides a risk of a hematoma, no other risks are foreseen. Volunteers
receive 10 euros for participation. Furthermore, volunteers will be told and
given advice if they turn out to suffer from an increased cardiovascular risk.