Download Coronary Heart Disease

Coronary Heart Disease
Prevalence and Risks of Undiagnosed Diabetes Mellitus in
Patients Undergoing Coronary Artery Bypass Grafting
Achim H. Lauruschkat, MD; Bert Arnrich, MS; Alexander A. Albert, MD; Jörg A. Walter, PhD;
Berthold Amann, MD; Ulrich P. Rosendahl, MD; Tejas Alexander, MD; Jürgen Ennker, MD
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Background—Numerous studies have shown that diabetes mellitus (DM) is not identified and, consequently, inadequately
treated in a substantial proportion of the patients in the general population. We know very little about the extent and the
consequences of undiagnosed diabetes in the risk group of patients with coronary heart diseases. The objective of this
study was therefore to determine the prevalence and the risks of undiagnosed DM among patients with coronary artery
bypass.
Methods and Results—The data of 7310 patients who have undergone coronary bypass operations between 1996 and 2003
were analyzed. Depending on their diagnosis on admission and their fasting plasma glucose (FPG) level, these patients
were classified as known diabetics, undiagnosed diabetics (FPG ⱖ126 mg/dL), or as nondiabetics (FPG ⬍126 mg/dL)
and were compared in terms of their preoperative, intraoperative, and postoperative characteristics. Among the patients
with coronary bypass that we examined, we found a prevalence of diagnosed diabetics of 29.6%. The prevalence of
patients with undiagnosed DM (FPG ⱖ126 mg/dL) was 5.2%. In comparison with the other groups (non-DM versus
undiagnosed DM versus known DM), the undiagnosed diabetics more frequently required resuscitation (1.7% versus
4.2% versus 1.5%; P⬍0.01) and reintubation (2.1% versus 5.0% versus 3.5%; P⬍0.01) and often showed a longer
period of ventilation ⬎1 day (5.6% versus 10.5% versus 7.4%; P⬍0.01). Perioperative mortality rate was highest in this
group (0.9% versus 2.4% versus 1.4%; P⬍0.01).
Conclusions—This study is the first to publish the prevalence of undiagnosed diabetes mellitus in cardiac surgery. During
the perioperative and postoperative courses, these patients displayed a substantially higher morbidity and mortality rate.
(Circulation. 2005;112:2397-2402.)
Key Words: coronary disease 䡲 diabetes mellitus 䡲 diagnosis 䡲 mortality 䡲 risk factors
A
s early as 1974, the epidemiological data of the Framingham study have shown that diabetes mellitus—
even after accounting for concomitant factors such as age,
gender, body mass index (BMI), hypercholesterolemia, nicotine abuse, and arterial hypertension—is one important
independent risk factor for the genesis of cardiovascular
diseases.1,2 Compared with the standard population, diabetics
have as much as a 2 to 3 times greater frequency of disorders
of the cardiovascular system.2 Cardiovascular mortality rate
among diabetics is 3 times higher than in the standard
population.3 Even in cases of disturbances of the glucose
tolerance without clinical diabetes mellitus, coronary insufficiency has been shown to have a higher incidence, and
asymptomatic hyperglycemia has been shown to entail a
substantially higher risk of cardiovascular death.4 In the
perioperative and postoperative courses of coronary bypass
operations, diabetic patients are often at a disadvantage
compared with nondiabetic patients. Hospital mortality
among diabetics is significantly increased; patients with
diabetes mellitus had postoperative strokes more often and
spent, on average, more days in hospital.5 The data of the
Second National Health and Nutrition Examination Survey
demonstrate a prevalence of diabetes mellitus in the population of the United States of 2% in the group 20 to 34 years of
age, with an increase of almost 20% among the patients
between 65 and 74 years of age. Among approximately 50%
of the diabetics in all age groups, the disease had not been
previously diagnosed at the time the study was conducted.6
Since that time, numerous studies on the prevalence of
undiagnosed diabetes mellitus have been published.4,7–9 Current data from Germany show a prevalence of diabetes
mellitus of 16.6% among the age group 55 to 74 years, again
with the disease having gone unnoticed in half the cases.10
However, we know very little about the extent and the
consequences of undiagnosed diabetes mellitus in high-risk
groups such as patients with coronary heart diseases. No
Received January 7, 2005; revision received July 23, 2005; accepted July 25, 2005.
From the Departments of Cardiac, Thoracic, and Vascular Surgery (A.A.L., A.A.A., U.P.R., J.E.), and Anaesthesiology (T.A.), Heart Institute
Lahr/Baden, Lahr; Neoinformatics Group, Faculty of Technology, Bielefeld University, Bielefeld (B. Arnrich, J.A.W.); and Fraziskus Hospital Berlin,
Berlin (B. Amann), Germany.
Correspondence to Dr med Achim H. Lauruschkat, Department of Cardiac, Thoracic, and Vascular Surgery, Heart Institute Lahr/Baden, Hohbergweg
2, 77933 Lahr, Germany. E-mail [email protected]
© 2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/CIRCULATIONAHA.105.534545
2397
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October 18, 2005
studies have to date been published on the prevalence of
undiagnosed diabetes mellitus in coronary bypass patients
and its impact on the perioperative and postoperative results.
Methods
The study included 7310 patients who had undergone coronary
bypass operations at the Heart Institute Lahr/Baden in the period
between January 1996 and June 2003. Emergency interventions,
combined procedures and “re-do” operations were excluded from the
study. Patient care, both at the operative and the postoperative stages,
followed the standardized guidelines of our hospital. For each patient
included in the present study, 32 preoperative characteristics and 8
postoperative progress values were used from the consolidated
database of our Data Mart system.11 The data were based on the
anesthesiological and cardiosurgical quality assurance and the laboratory data of the clinical chemistry.
Definitions
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The following definitions, essentially applied in analogy with the
EuroSCORE,12 were used for the risk factors investigated: peripheral vascular disease: claudication, previous or planned intervention
involving the arteries of the limbs; carotid disease: carotid occlusion
or ⬎50% stenosis, previous or planned intervention on the carotids;
neurological dysfunction: severely affecting ambulation or day-today functioning; chronic obstructive pulmonary disease (COPD):
long-term use of bronchodilators or steroids for lung disease;
pulmonary hypertension: systolic pulmonary artery pressure
⬎60 mm Hg; recent myocardial infarction: myocardial infarction
occurring within 90 days; unstable angina: rest angina requiring
intravenous nitrates until arrival in the anesthetic room (patients who
were not fully without symptoms under intravenous nitrate medication were declared as “emergency cases” and excluded from the
study); stroke: a new focal neurological deficit or coma lasting more
than 24 hours, associated with computed tomographic demonstration
or recent ischemic cerebral lesion; and cerebral dysfunction: in
comparison with the preoperative status, abnormality in behavior and
temporal and spatial disorientation that are also clinically conspicuous without specific psychiatric examinations. Diabetes was diagnosed by using the current recommendations by the American
Diabetes Association: The determination of the diabetes status in
epidemiological studies is based on the measurement of the fasting
plasma glucose level (FPG ⱖ126 mg/dL [7.0 mmol/L]).13 Patients
admitted and diagnosed with diabetes mellitus or treated with oral
antidiabetic agents or with insulin before their admission were
assessed as having known diabetes. Depending on their FPG level,
the remaining patients were classified either as having undiagnosed
diabetes (FPG ⱖ126 mg/dL) or as having no diabetes (FPG ⬍126
mg/dL). These groups of patients were compared in terms of their
preoperative characteristics and risk factors and the data of their
postoperative progress.
Statistical Analysis
Univariate comparisons between the 3 patient groups investigated
(known diabetics, undiagnosed diabetics, and nondiabetics) were
performed by using the ␹2 test for categorical variables and the
Mann-Whitney test for continuous variables (SPSS, 12.0). Stepwise
logistic regression was used to determine the predictors of the
hospital outcomes of interest by minimizing the so-called Akaike
Information Criterion. All baseline attributes and 2 additional dichotomous indicator variables encoding the diabetes status were initially
used in the regression tasks. To obtain a nondiabetic reference group,
the 2 indicator variables were defined as follows: known diabetes
mellitus⫽1 for diagnosed diabetes, 0 otherwise, and undiagnosed
diabetes mellitus⫽1 for undiagnosed diabetes, 0 otherwise. In cases
where only 1 indicator variable remained significant in the final
model, the counterpart was forced into the model respectively.
Model discrimination was evaluated by the area under the receiver
operating characteristic curve.
TABLE 1.
Patient Distribution
FPG
n (%)
No diabetes
⬍126mg/dL
4.769 (65.2)
Undiagnosed diabetes
ⱖ126mg/dL
380 (5.2)
Known diabetes
2.161 (29.6)
⌺
7.310 (100)
FPG indicates fasting plasma glucose.
Results
Table 1 shows the distribution of the patients we investigated
according to the diagnostic criteria applied. The demographic
and clinical characteristics of the nondiabetic coronary patients versus the undiagnosed diabetics and the known diabetics are shown in Table 2.
Baseline Characteristics
On average, diabetic coronary patients in cardiac surgery
were significantly older then nondiabetic patients. Women,
patients with a higher BMI, and patients with arterial hypertension were significantly overrepresented among the diabetic patients. In this respect, the undiagnosed diabetics did
not differ significantly in all aspects from nondiabetic patients, but their data tended to lie between the nondiabetic
patients and diagnosed diabetics. Known and undiagnosed
diabetics had a significantly higher prevalence of peripheral
vascular disease than did nondiabetics. A history of strokes
was most frequently found among the group with known
diabetes. These patients also had COPD significantly more
often than did patients with undiagnosed diabetes and nondiabetic patients with coronary disease.
Clinical Cardiac Parameters and
Angiographic Findings
Diabetic patients were more frequently admitted to cardiac
surgery with New York Heart Association functional class IV
symptoms than were nondiabetic patients, but the highest
proportion of patients in NYHA functional class IV was
found among the undiagnosed diabetics (8.4% undiagnosed
diabetes mellitus versus 6.0% no diabetes mellitus; P⫽0.06).
Patients with restricted left ventricular ejection fraction were
found significantly more often among the known diabetics,
whereas the known diabetics and the undiagnosed diabetics
showed a significantly higher prevalence of coronary 3-vessel
diseases than did nondiabetic patients with coronary disease.
The frequency of main stem stenoses showed a declining,
downward tendency from nondiabetics to undiagnosed diabetics and known diabetics.
Laboratory Parameters
On average, the diabetic group of patients showed higher
leukocyte values than those of the nondiabetic patients. Also,
we found the highest total cholesterol values among the group
of undiagnosed diabetics. The renal function tests (creatinine,
urea) showed a rising tendency from nondiabetics over
undiagnosed diabetics to known diabetics.
Medication
The medication history also showed a certain heterogeneity.
Known diabetics have been treated before surgery more often
Lauruschkat et al
Undiagnosed Diabetes Mellitus in Cardiac Surgery
TABLE 2. Baseline Characteristics for the 3 Patient Groups in
Percent or as Group Average (With Units)
No Diabetes
(n⫽4769)
Undiagnosed
Diabetes
(n⫽380)
Known
Diabetes
(n⫽2161)
Age, y
65.09
66.34*
66.58†
Female sex, %
21.2
25.5
32.4†§
Body mass index, kg/m2
27.46
27.92†
28.61†§
73.4
75.0
83.6†§
Peripheral vascular disease, %
8.1
12.6†
14.4†
Carotid disease, %
9.1
11.1†
12.7†
Past stroke, %
6.2
5.3
9.1†‡
Neurological dysfunction, %
6.2
6.1
10.2†‡
19.4
19.5
26.0†§
2.6
2.1
3.4
Recent myocardial infarction, %
23.7
28.9*
26.9†
Unstable angina, %
10.4
14.5*
9.8§
6.0
8.4
7.7†
28.0
30.8
36.9†‡
3.6
2.4
5.8†
Demographic profile
Medical history
Hypertension, %
COPD, %
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Pulmonary hypertension, %
NYHA class 4, %
Ejection fraction, 30%–50%, %
Ejection fraction ⬍30%, %
Angiographic characteristics
1-Vessel disease, %
10.5
2-Vessel disease, %
32.7
6.1†
29.5
6.8†
28.9†
3-Vessel disease, %
49.0
59.5†
57.3†
Main stem disease, %
19.5
17.9
16.5†
13.95
13.94
13.59†§
Laboratory parameters
Hemoglobin, g/dL
Erythrocytes, 10 /␮L
6
Thrombocytes, 103/␮L
Leukocytes, 103/␮L
Total cholesterol, mg/dL
Creatinine, mg/dL
4.53
234.5
7.61
203.7
4.54
234.4
8.03†
212.0†
4.46†§
234.6
7.90†
197.5†§
1.13
1.19†
1.21†
Urea, mg/dL
38.77
43.41†
45.49†§
Creatine kinase, U/L
44.14
43.85
44.35†
ACE inhibitors, %
47.0
43.9
59.9†§
Aspirin, %
25.6
25.0
24.1
␤-Blockers, %
69.1
63.4*
64.5†
Diuretics, %
17.6
21.6
31.9†§
Nitrates, %
62.0
62.1
61.5
Medications
Tests on group equivalence are performed by using the ␹2 test (for categorical
data) and Mann-Whitney test (for continuous variables). Significant difference of
undiagnosed or known diabetes to no-diabetes group: *P⬍0.05, †P⬍0.01.
Significant difference of known diabetes to undiagnosed diabetes group:
‡P⬍0.05, §P⬍0.01.
n indicates No. of cases remaining after listwise deletion of cases with any
missing values (initial frequencies: age, 0.1%; body mass index, 0.2%; carotid
disease, 3.4%; past stroke, 4.8%; chronic obstructive pulmonary disease,
3.4%; pulmonary hypertension, 1.8%; recent myocardial infarction, 3.1%; New
York Heart Association class IV, 1.8%; hemoglobin, 2.2%; erythrocytes, 2.5%;
thrombocytes, 2.4%; leukocytes, 2.7%; total cholesterol, 3.8%; creatinine,
2.2%; urea, 2.7%; creatine kinase, 2.2%; ACE inhibitors, 2.6%; aspirin, 2.6%;
␤-blockers, 2.6%; diuretics, 2.6%; nitrates, 2.6%; others, 0%).
TABLE 3.
2399
Hospital Outcome
Outcome
No
Diabetes
Undiagnosed
Diabetes
Known
Diabetes
Cardiopulmonary resuscitation, %
1.7
4.2†
1.5§
Renal failure–dialysis, %
1.7
2.9
4.8†
Stroke, %
1.4
2.1
2.3†
Cerebral dysfunction, %
4.7
6.3
8.2†
Reintubation, %
2.1
5.0†
3.5†
Ventilation time ⬎1 day, %
5.6
10.5†
7.4†‡
27.0
28.7
35.1†‡
Intensive care unit stay ⬎3 days, %
30-Day mortality rate, %
0.9
2.4†
1.4*
Significant difference of undiagnosed or known diabetes to no-diabetes
group: *P⬍0.05, †P⬍0.01.
Significant difference of known diabetes to undiagnosed diabetes group:
‡P⬍0.05, §P⬍0.01.
with ACE inhibitors and diuretics, whereas the nondiabetic
patients with coronary disease had been given ␤-blockers
more often than the diabetic patient groups.
Hospital Outcome
At the postoperative stage, undiagnosed diabetics needed
resuscitation significantly more often than the other patients
groups examined (no diabetes mellitus, 1.7% versus undiagnosed diabetes mellitus, 4.2% versus known diabetes mellitus, 1.5%), see Table 3. Among the known diabetic patients
with coronary disease, postoperative renal failure requiring
dialysis occurred significantly more often (4.8%) than in
nondiabetics (1.7%) or the undiagnosed diabetics (2.9%).
Perioperative strokes occurred more often among diabetic
patients with coronary disease (2.3%) than among nondiabetics (1.4%). Also, cerebral dysfunction occurred significantly
more often among these patients (8.2%) than in nondiabetic
patients with coronary disease (4.7%).
Diabetics required postoperative reintubation more often
(3.5%) than nondiabetics (2.1%), with the rate of reintubation
being highest among the undiagnosed diabetics (5.0%). The
number of patients requiring respiration for periods longer
than 1 day was also highest among these patients (no diabetes
mellitus, 5.6%, versus undiagnosed diabetes mellitus, 10.5%,
versus known diabetes mellitus, 7.4%). The number of
patients staying in the intensive care unit for postoperative
periods longer than 3 days was highest among the known
diabetics (no diabetes mellitus, 27.0%, versus undiagnosed
diabetes mellitus, 28.7%, versus known diabetes mellitus,
35.1%). Known and undiagnosed diabetics showed a significantly higher 30-day mortality rate, with the highest mortality rate found in the group of undiagnosed diabetics (no
diabetes mellitus, 0.9%, versus undiagnosed diabetes mellitus, 2.4%, versus known diabetes mellitus, 1.4%).
Table 4 shows the 4 resulting stepwise logistic regression
models for hospital outcomes in which undiagnosed diabetes
remained significant in the final model. The results show that
undiagnosed diabetes mellitus can be considered as an independent risk factor for (1) longer respiration times, (2) more
frequent reintubations, (3) resuscitation at the postoperative
stage, and (4) an increased 30-day mortality rate.
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Circulation
October 18, 2005
TABLE 4. Logistic Regression Analysis for the 4 Outcomes in
Which Undiagnosed Diabetes Remained Significant in the
Final Model
No. of
Events
Crude
OR
Adjusted
OR
95% CI
P
Undiagnosed DM
16
2.51
2.38
1.37–4.15
⬍0.01
Known DM
33
0.89
0.78
0.52–1.19
0.25
Undiagnosed DM
19
2.41
1.89
1.12–3.19
0.02
Known DM
76
1.67
1.25
0.92–1.72
0.16
40
1.98
1.75
1.21–2.53
⬍0.01
159
1.33
1.01
0.82–1.26
0.90
9
2.80
2.23
1.04–4.79
0.04
31
1.68
1.17
0.72–1.91
0.54
Diabetes Status
Cardiopulmonary
resuscitation*
Reintubation†
Ventilation time ⬎1 day‡
Undiagnosed DM
Known DM
Mortality§
Undiagnosed DM
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Known DM
For each outcome, the crude OR (resulting from simple logistic models
where only the 2 indicator variables undiagnosed diabetes mellitus 关DM兴 and
Known DM were included) and the adjusted OR with additional covariates and
the area under the receiver operating curve (ROC) given in the footnote are
presented. Confidence intervals and P values correspond to the adjusted
models, respectively.
*Further covariates (full model): Age, carotid disease, leucocytes, creatine
kinase, unstable angina, main stem disease, left ventricular ejection fraction
(LVEF) ⬍30%; area under ROC, 0.68.
†Further covariates (full model): Age, chronic obstructive pulmonary disease
(COPD), leucocytes, creatine kinase, urea, unstable angina, LVEF 30% to 50%,
LVEF ⬍30%, ␤-blockers; area under ROC, 0.69.
‡Further covariates (full model): Age, COPD, neurological dysfunction,
leucocytes, creatine kinase, urea, unstable angina, recent myocardial infarction, total cholesterol, 2-vessel disease, LVEF 30% to 50%, LVEF ⬍30%,
␤-blockers; area under ROC, 0.70
§Further covariates (full model): Age, past stroke, COPD, leukocytes, urea,
main stem disease, LVEF 30% to 50%, LVEF ⬍30%; area under ROC, 0.77.
the group of undiagnosed diabetics.8,9,16 The observation that
diabetic patients with coronary disease have peripheral vascular disease significantly more often is also described by
other authors.17,18 Stroke in the patient history was found
significantly more often among the group of known diabetics.
The more advanced age of diabetic patients must be taken
into account in this context, considering that it is accompanied by advancing atherosclerosis, the higher risk of embolic
events, and by changes in the cerebral vessels and in the
blood flow autoregulation.19
Clinical Cardiac Parameters and
Angiographic Findings
The data obtained in the present study demonstrated that
diabetics are more frequently admitted with NYHA functional class IV symptoms and often have a lower ejection
fraction than nondiabetic patients with coronary disease.
These results are consistent with the observations made by
many other authors.1,5,17,20 Patients with a longer duration of
the diabetic disorder more often showed signs of diabetic
neuropathy, which, in turn, may result in myocardial infarctions progressing painlessly or atypically or manifest themselves as cardiac insufficiency, cardiac shock, or arrhythmia.21 This means that the diagnosis is more difficult and that
the adequate therapy is often initiated with a delay. Zarich et
al22 reported that more than 90% of the ischemic episodes
progressed asymptomatically among the diabetic patients
they observed. This high number of asymptomatic ischemic
episodes could result in these patients later being diagnosed
as nondiabetic and consequently admitted to cardiac surgery
at an advanced stage of coronary heart disease. Consequently,
we found a significantly higher number of patients with
coronary 3-vessel disease among the diabetic coronary patients (see Table 2).
Laboratory Parameters and Medication
The prevalence of diagnosed diabetes mellitus in the patient
population investigated by us was 29.6%. The prevalence of
undiagnosed diabetes was 5.2%. Taking these patients into
consideration, the total share of diabetic patients with coronary disease rose to 34.8%. Abramov et al14 reported a
consistent rise in the prevalence of diabetes among patients
with coronary bypass in recent years from 18.6% (1990) to
26.7% (1998). The reasons for this phenomenon are found in
demographic changes and changes in the assignment modalities but may also suggest more comprehensive preoperative
diagnoses in younger years.
The highest mean total cholesterol values (see Table 2) were
found among the group of undiagnosed diabetics, a result that
is also reported by other authors9,16 and could suggest that
these patients have hitherto not been treated commensurately
with their risk profile. ACE inhibitors and diuretic medication
is found significantly more often among the known diabetic
patients with coronary disease (unfortunately, proper data on
statin medication were not available).
The progressive abnormalities in renal function tests as
seen in diabetics compared with undiagnosed diabetics is not
surprising, as a higher incidence of diabetic nephropathy
would be expected among those having diabetes for a longer
time.
Baseline Characteristics
Hospital Outcome
Diabetic patients showed a significantly higher prevalence of
the known cardiovascular risk factors such as raised BMI,
age, and arterial hypertension. The results obtained by Taubert et al15 show a progression of cardiovascular risk factors
over the various categories ranging from “nondiabetics” over
“undiagnosed diabetics” through to “known diabetics.” The
data from other authors showed a higher prevalence of
overweight and other cardiovascular risk factors, mainly in
The results of the present study showed that neurological
damage and states of disorientation in the postoperative
course of coronary bypass operations occurred significantly
more often among known diabetics. Studies have demonstrated that diabetics show subclinical but objectively measurable impairments of the cognitive cerebral functions23 that
correlate directly with the duration of the disorder.24 These
patients are particularly at risk during cardiac surgery inter-
Discussion
Lauruschkat et al
Undiagnosed Diabetes Mellitus in Cardiac Surgery
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ventions. Other authors report that diabetics, in the perioperative course of a bypass operation, are significantly more at
risk of having strokes and transient ischemic attacks to fall
into permanent coma or to die from stroke or hypoxic
encephalopathy.19,25,26 Potential causes include cerebrovascular autoregulation impaired in diabetics under the extracorporeal circulation and a generalized atherosclerosis affecting
the aorta, the carotids, and the cerebral arteries. The significantly longer average ventilation time and the high number of
reintubations of diabetic patients at the postoperative stage,
even after accounting for risk factors such as age, BMI,
preexisting COPD, and so forth, was also remarkable. These
results are explicable if the lung as a target organ of diabetic
microangiopathy is also taken into account.27 Pathological
studies involving diabetics found basal lamina thickening
both of the alveolar epithelium and of the capillary endothelium.28 Pulmonary dysfunctions— clinically inconspicuous
under normal conditions— could, as it were, be “unmasked”
by the “capillary leak” and other pathophysiological conditions developing after the use of extracorporeal circulation.
The rise in hospital mortality rates of diabetic patients that
we observed is also reported by other authors.5 Remarkably,
the highest mortality rate was found among the group of
undiagnosed diabetics. It should be noted, however, that these
patients—as shown in Table 2— have a characteristic risk
profile without, however, having been appropriately treated
as known diabetics. With regard to their vascular status
(peripheral vascular disease, carotid disease, past stroke),
undiagnosed diabetics appear to be less predisposed than
diagnosed diabetics. With regard to the cardiovascular risk
factors (age, BMI, arterial hypertension, and so forth) these
patients stand between the known diabetics and the nondiabetics. These findings suggest a briefer duration of the
disease, which may also explain the omitted diagnosis,
particularly because type 2 diabetes is, on average, often
diagnosed with a delay of as much as 7 years after the actual
onset of the disease.29 The results of the present study show,
however, that these patients are exposed to a particularly high
risk in the perioperative and postoperative course of coronary
bypass operations. It should be noted that the patients we
examined do not constitute just any random sample from the
total population but, by virtue of their coronary heart disease,
have passed through a selection process that also involved
extensive preoperative diagnostics before their admission to
cardiac surgery. The fact that the proportion of undiagnosed
diabetics was so large among these patients may be surprising
but is explicable: Levetan et al30 examined 1034 internistic
and surgical hospitalized patients in an inner-city tertiary-care
teaching hospital in Washington, DC, and found a rate of
33% of diabetics undiagnosed at the time of admission among
the hyperglycemic patients. What surprised the investigators,
however, was the discovery that only 7.3% of the previously
undiagnosed diabetics were actually diagnosed in the continued course of their hospital stay. The treating physicians
presumably believed the cause of the increased blood sugar
values to be more a “stress hyperglycemia” as an expression
of the acute disease rather than considering the diagnosis of a
previously undetected diabetes mellitus. The problem may
have been that there are as yet no uniform diagnostic criteria
2401
or recommendations for a definite diabetes diagnosis in
situations of clinical stress. Husband et al31 examined patients
admitted with suspected acute myocardial infarction and
showing increased level of plasma glucose. Among these
patients, whose glucose values would certainly have been
interpreted often as “stress hyperglycemia” on inpatient
admission, a normal glucose tolerance was found in one third
of the patients during the follow-up check 1 month later. The
study by Norhammar et al32 in the year 2002 confirmed these
findings.
In view of the high risk that this disease entails, especially
for patients with coronary disease, clinicians are urgently
advised to rate hyperglycemia as diabetes mellitus until proof
to the contrary is shown.
Because the patient population is not very different from
other national heart institutes, the hypothesis arises that our
finding can be generalized to a wider field of patients with
cardiac disease in the Western industrialized world.
The high proportion of undiagnosed diabetics among
patients with coronary disease that we observed could also
have some relevance in the analysis of earlier studies. In the
past, numerous major studies have tried to establish which
revascularization method— bypass surgery or the methods of
interventional cardiology (PTCA/stenting)— delivers better
results. The investigators of the Bypass Angioplasty Revascularization Investigation (BARI) reported that in the 5-year
survival, there were no significant differences between these
therapy strategies.33 However, the infarction mortality rate in
the subgroup of patients with diabetes mellitus assigned to the
coronary surgery group was significantly lower than that in
the PTCA group.34 The results of the Northern New England
Cardiovascular Disease Study Group,35 published later, and
of the Arterial Revascularization Therapy Study (ARTS)36,37
confirmed that coronary surgery leads to significantly better
results in diabetic patients. The issue common to all these
studies is that the “diabetes mellitus” status was acquired only
under categorical terms. The decisive factor in the assignment
to this group was the diagnosis made by the admitter, the
information given by the patient during anamnesis, and the
documented therapy using oral antidiabetic agents or insulin
therapy. No objective data such as the FPG values were
obtained. The possibility that there might be a relevant group
of undiagnosed diabetics was obviously ignored in these
studies. One may therefore assume that the unidentified
diabetics in the group of the “nondiabetics” will show a
pronounced drop in the observable differences between diabetic and nondiabetic patients with coronary disease. Considering the observed high prevalence of undiagnosed diabetics
among patients with coronary disease, the conclusion seems
evident that diabetics could benefit to a greater extent than
previously assumed from bypass operations versus the measures of interventional cardiology.
Furthermore, it is highly recommended that clinical practice and future studies focus on the possibly concealed factor
of diabetes mellitus, which can be easily detected by measuring the FPG concentration. Our study emphasizes the importance of this general advice of the American Diabetes
Association for the field of coronary surgery.
2402
Circulation
October 18, 2005
Acknowledgment
The authors thank Sarah Ganter, Renate Böhmer, Peter Mühlecker,
and Ulrike Ritzau (Heart Institute Lahr/Baden) for expert help with
data collection.
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Circulation. 2005;112:2397-2402
doi: 10.1161/CIRCULATIONAHA.105.534545
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