Mannose-binding lectin genotype and phenotype and their impact on
cardiovascular prognosis in patients with type 2 diabetes and myocardial
infarction: a report from the DIGAMI 2 trial
L. Mellbin1, L. Ryden1, A. Hamsten1, K. Malmberg1, R. Steffensen2, J. Ohrvik1, T K. Hansen2
(1) Department of Medicine, Karolinska Institutet, Stockholm, Sweden (2) Aalborg Hospital of the Aarhus University Hospital, Aalborg, Denmark
Conclusions
In patients with type 2 diabetes and myocardial infarction:
- MBL genotypes are similar to those known in the general population.
- The combination of a low-coding MBL genotype with a low S-MBL appears
prognostically unfavorable, but the association is blunted by traditional risk markers.
MBL
Anti-MBL
Agalactosyl IgG
Tissue sugar
Figure 2
Results
The present study characterizes
mannose-binding lectin (MBL), an
activator of the complement
system and thereby important for
inflammatory activation, in patients
with type 2 diabetes (DM) and
myocardial infarction (MI).
Median S-MBL was 1212 μg/l (IQR 346-2681 μg/l).
The distribution of geno- and phenotypes are
shown in figure 1. S-MBL did not correlate with
age, BMI, creatinine clearance, glucose or HbA1c.
CVE occurred in 136 (35%) patients.
S-MBL did not predict events in univariable
analyses (HR 0.93;CI 95% 0.85-1.01; p=0.09).
1.0
Survival free from CVE
Aims
MBL
Genotype/Conc
High and Above (n=78)
High and Below (n=78)
Low and Above (n=65)
Low and Below (n=66)
0.9
0.8
0.7
0.6
0.5
0
Figure 1
High genotype (AA;54%):S-MBL median 2658 µg/l (IQR 1714 – 3828)
Low genotype( AO+OO; 46% ):S-MBL median 373 µg/l (IQR 100 - 765)
Baseline S-MBL
Methods
Serum (S)-MBL was determined
at hospital admission in 387
patients with DM and MI
(median age 70 years; males 68%).
Genotyping was performed in 287
patients. Cardiovascular events
(CVE = cardiovascular mortality
and non-fatal MI or stroke) were
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Accepted for publication in Diabetes Care (Epub ahead of print; 2010 Aug 6)
AO
Genotype
OO
5
10
15
20
25
30
35
Follow up (months)
In unadjusted analyses, the risk of events was
lower in patients with a high genotype and SMBL above the median for their genotype (HR
0.49; 95% CI 0.26-0.92; p= 0.026) than for
patients with a low genotype and S-MBL below
the median for their genotype (Figure 2). The
prediction capacity of the geno- and phenotype
model was of borderline significance in
adjusted Cox regression (p=0.07).
e-mail: [email protected]