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SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 8 NUMBER 2 • JUNE 2011
63
Male and female patients aged 55 or older with suspected
or overt CHD undergoing elective coronary angiography were
eligible for study participation. Patients with acute gastrointestinal
infection, acute feverish illness, suspected of medication, drug or
alcohol abuse or without legal capacity were excluded from the
trial. Prevalence of macrovascular disease (myocardial infarction,
stroke, angina pectoris, peripheral or coronary artery disease) was
assessed by a standardised questionnaire.
The collection of data and of the blood samples was performed
in one day but before angiography. The patient was in an overnight
fasting state from the evening onward before they arrived at the
study site. Blood was drawn for the measurement of the efficacy
of laboratory parameters from all patients to determine several risk
biomarkers. Body weight, height, waist and hip circumference and
blood pressure were recorded using standardised methods. In all
patients without known diabetes or without confirmed random
plasma glucose at admission equal or above 200 mg/dl, a 75-g oral
glucose tolerance test (OGTT) was performed under standardised
fasting conditions. T2D was diagnosed according to current
international guidelines.
Laboratory procedures
All laboratory variables were determined in the central laboratory at
the Institute for Clinical Research and Development (IKFE) by using
standard methods according to the corresponding manufacturer’s
instructions. Plasma glucose was determined enzymatically
(SuperGL, RLT, Möhnesee-Delecke, Germany), high-sensitive
C-reactive protein with an enzyme immuno assay (MP Biomedicals,
LLC, Eschwege, Germany), and HbA
1c
was measured colorimetrically
with an automatic glycohaemoglobin analyser (AdamsTM A
1c
,
HA-8160 Kit, Menarini Diagnostics, Neuss, Germany). Lipids
(triglycerides, total cholesterol, high-density lipoprotein cholesterol,
low-density lipoprotein cholesterol) were measured by photometry.
Standard enzyme-linked immunosorbent assays (ELISAs) supplied by
R&D systems (Minneapolis, USA) were used to quantify monocyte
chemoattractant protein-1 (MCP 1), interleukin-6 (IL-6), matrix
metallo proteinase-9 (MMP-9), soluble CD 40 ligand (sCD40L),
soluble intracellular adhesion molecule (sICAM), soluble vascular
adhesion molecule (sVCAM), and E-selectin. Insulin and intact
proinsulin were determined by ELISA (Metascreen, TecoMedical,
Sisslach, Switzerland).
Data analysis
Statistical analysis was performed using standard descriptive
statistics and appropriate parametric and non-parametric tests. The
means of the variables were compared using two-sided Student’s
t
-test.
p
-values
<
0.05 were considered statistically significant.
Results
In total, 530 patients were enrolled in this study from 22 cardiology
centres throughout Germany. The study cohort consisted of 181
male and 349 female patients with a mean age (
±
SD) of 68
±
7 years; 156 patients (29.4%) had known diabetes and 184
patients (34.7%) had no diabetes; 106 patients (20.0%) suffered
from IGT or IFG whereas 84 patients (15.9%) were newly
diagnosed for diabetes. Within these groups, the patients were
equally distributed according to age, gender and intake of anti-
hypertensive drugs with moderate but insignificantly reduced
values in the group of patients without diabetes (age: no diabetes
66.9
±
7.2 years, known diabetes 68.5
±
7.4 years, IGT/IFG 68.7
±
7.3 years, newly diagnosed diabetes 68.3
±
7.7 years; gender:
no diabetes 115 females (62.5%) and 69 males (37.5%), known
diabetes 101 females (64.7%) and 55 males (35.3%), IGT/IFG 78
females (73.6%) and 28 males (26.4%), new diabetes diagnosis
55 females (65.5%) and 29 males (34.5%); patients treated with
anti-hypertensives: no diabetes 116 (63.0%), known diabetes 132
(84.6%), IGT/IFG 91 (86%), new diabetes diagnosis 68 (81.0%)).
Table 1 shows the higher prevalence of a history of macrovascular
events in patients with abnormalities in glycaemic homeostasis
compared with patients without diabetes. It is noteworthy that
only the IFG/IGT group showed significantly increased occurrence
of previous macrovascular events. This was not the case in
diabetic patients, but this result might be traced back to the total
number of enrolled patients. Risk marker data from patients with
abnormalities in glucose homeostasis were then compared with the
data from patients without diabetes. Table 2 displays the significant
differences of several markers between the groups. Insulin
resistance as assessed by homeostasis model assessment (HOMA)
score was significantly lower in the group without diabetes. The
glycaemic profile (HbA
1c
, fasting blood glucose) showed the
expected significant deterioration in all groups compared with the
‘no diabetes’ cohort. The other parameters are considered to be
cardiovascular risk markers (MMP-9, MCP-1, ICAM, VCAM, lipids)
or markers of chronic inflammation (hsCRP, IL-6). The cardiovascular
risk is increased in both groups of patients with diabetes displayed
by significant augmentation of hsCRP, adhesion molecules and
MMP-9. It is of interest that patients with IGT/IFG have also a higher
risk according to the pattern of the surrogate markers MMP-9,
ICAM, VCAM, sCD40L, MCP-1, E-selectin and IL-6.
Discussion
The prevalence of diabetes is projected to rise substantially
and to a greater extent than estimated previously.
2
It is far from
demonstrated that reducing plasma glucose prospectively translates
into reduced cardiovascular morbidity/mortality. Targeting the
common underlying causes of glycaemic elevation and CHD seems
on the other hand to have a substantial rationale.
3
Together with
the data that complications, in particular concerning macrovascular
events, account for the majority of deaths among the diabetes
population,
4
it is clear that early diagnosis and treatment of
metabolic abnormalities can be a powerful tool for healthcare
systems to save lives and, additionally, to save costs as a favourable
secondary objective.
1
Recently, the European Heart Survey, which included 110 centres
in 25 countries, demonstrated that in patients with manifest CHD,
Table 1.
Prevalence of macrovascular events in the entire study
cohort. Data were obtained anamnestically by a standardised
questionnaire. Significance was assessed by statistical calculation
of the ‘no diabetes’ group versus each single other cohort.
Significance niveau (
p
-value)
Known diabetes
65.40%
0.2438
IFG/IGT
69.60%
0.0257
New diagnosis
72.60%
0.0771
No diabetes
58.20%
