Increased preoperative glucose levels are associated with perioperative mortality in patients undergoing noncardiac, nonvascular surgery.
ABSTRACT To determine the relationship between preoperative glucose levels and perioperative mortality in noncardiac, nonvascular surgery.
We performed a case-control study in a cohort of 108 593 patients who underwent noncardiac surgery at the Erasmus MC during 1991-2001. Cases were 989 patients who underwent elective noncardiac, nonvascular surgery and died within 30 days during hospital stay. From the remaining patients, 1879 matched controls (age, sex, calendar year, and type of surgery) were selected. Information was obtained regarding the presence of cardiac risk factors, medication, and preoperative laboratory results. Preoperative random glucose levels <5.6 mmol/l (110 mg/dl) were normal. Impaired glucose levels in the range of 5.6-11.1 mmol/l were prediabetes. Glucose levels >or=11.1 mmol/l (200 mg/dl) were diabetes.
Preoperative glucose levels were available in 904 cases and 1247 controls. A cardiovascular complication was the primary cause of death in 207 (23%) cases. Prediabetes glucose levels were associated with a 1.7-fold increased mortality risk compared with normoglycemic levels (adjusted odds ratio (OR) 1.7 and 95% confidence interval (CI) 1.4-2.1; P<0.001). Diabetes glucose levels were associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3-3.5; P<0.001). In cases with cardiovascular death, prediabetes glucose levels had a threefold increased cardiovascular mortality risk (adjusted OR 3.0 and 95% CI 1.7-5.1) and diabetes glucose levels had a fourfold increased cardiovascular mortality risk (OR 4.0 and 95% CI 1.3-12).
Preoperative hyperglycemia is associated with increased (cardiovascular) mortality in patients undergoing noncardiac, nonvascular surgery.
- SourceAvailable from: Antonio Amor[Show abstract] [Hide abstract]
ABSTRACT: Background and objective The management of hyperglycemia in conventional wards is suboptimal. The objective of our study was to evaluate the efficacy of a proactive intervention supported by point-of-care system with remote viewing of capillary blood glucose (CBG) on glycemic control as compared to usual care in non-critical surgical patients. Patients and method Two sequential periods of 2 months were defined. In the first phase (control, CPh), in which the surgical team was in charge of glycemic control, capillary glucose levels were recorded by StatStrip® system, and endocrinological support was provided upon surgeons request. In a second phase (intervention, IPh), the endocrinologist proceeded based on remotely-viewed CBG values. We compared the use of basal-bolus therapy and the degree of glycemic control between the 2 study periods. Results The IPh was associated with greater use of basal-bolus regimens (21.4 vs. 58.3%; P = .003). The average CBG during the CPh was 161 ± 64 vs. 142 ± 48 mg/dL during the IPh (P < .001). The IPh was associated with an increased frequency of CBG determinations between 70-140 mg/dL (CPh: 41.8 vs. IPh: 52.5%; P < .001), lower frequency of ≥ 250 mg/dL CBG determinations (CPh: 9 vs. IPh: 3.5%; P < .001), with no increase in the frequency of hypoglycemia (CPh: 3 vs. IPh: 3.7%; P = .39). Conclusions A proactive endocrine intervention facilitated by a point-of-care system with remote viewing of CBG is associated with improved glycemic control in non-critical patients, without any further increase in the number of hypoglycaemic recordings.Medicina Clínica 05/2014; 142(9):387–392. · 1.25 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Heavy-ion induced upsets are compared in dual-well and triple-well 40 nm CMOS SRAMs. Charge confinement in triple-well structures triggers the single-event upset reversal mechanism for high LET particles. Due to upset reversal, high LET ion-hits incident at off-normal angles show a de 1f0 crease in SER compared to normally-incident ions for triple-well SRAM cells.Reliability Physics Symposium (IRPS), 2012 IEEE International; 01/2012
- [Show abstract] [Hide abstract]
ABSTRACT: Intraoperative glycemic control, particularly in cardiac surgical patients, remains challenging. Patients with impaired insulin sensitivity and/or secretion (i.e., type 1 diabetes mellitus) often manifest extremely labile blood glucose measurements during periods of stress and inflammation. Most current insulin infusion protocols are developed based on clinical experiences and consensus among a local group of physicians. Recent advances in human glucose metabolism modeling have established a computer model that invokes algorithms representing many of the pathways involved in glucose dysregulation for patients with diabetes. In this study, we used an FDA approved glucose metabolism model to evaluate an existing institutional intraoperative insulin infusion protocol via closed-loop simulation on the virtual diabetic population that comes with the computer model. A comparison of simulated responses to actual retrospective clinical data from 57 type 1 diabetic patients undergoing cardiac surgery managed by the institutional protocol was performed. We then designed a proportional-derivative controller that overcomes the weaknesses exhibited by our old protocol while preserving its strengths. In-silico evaluation results show that our proportional-derivative controller more effectively manages intraoperative hyperglycemia while simultaneously reducing hypoglycemia and glycemic variability. By performing in-silico simulation on intraoperative glucose and insulin responses, robust and seemingly efficacious algorithms can be generated that warrant prospective evaluation in human subjects.Healthcare Informatics (ICHI), 2013 IEEE International Conference on; 01/2013
Increased preoperative glucose levels are associated with
perioperative mortality in patients undergoing noncardiac,
Peter G Noordzij, Eric Boersma2, Frodo Schreiner, Miklos D Kertai1, Harm H H Feringa, Martin Dunkelgrun1,
Jeroen J Bax3, Jan Klein and Don Poldermans
Departments of Anesthesiology,1Vascular Surgery, and2Cardiology, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam,
The Netherlands and3Department of Cardiology, University Hospital Leiden, Leiden, The Netherlands
(Correspondence should be addressed to D Poldermans; Email: firstname.lastname@example.org)
Objective: To determine the relationship between preoperative glucose levels and perioperative
mortality in noncardiac, nonvascular surgery.
Research design and methods: We performed a case–control study in a cohort of 108 593 patients who
underwent noncardiac surgery at the Erasmus MC during 1991–2001. Cases were 989 patients who
underwent elective noncardiac, nonvascular surgery and died within 30 days during hospital stay.
From the remaining patients, 1879 matched controls (age, sex, calendar year, and type of surgery)
were selected. Information wasobtained regarding the presence of cardiac risk factors, medication, and
preoperative laboratory results. Preoperative random glucose levels !5.6 mmol/l (110 mg/dl) were
normal. Impaired glucose levels in the range of 5.6–11.1 mmol/l were prediabetes. Glucose levels
R11.1 mmol/l (200 mg/dl) were diabetes.
Results: Preoperative glucose levels were available in 904 cases and 1247 controls. A cardiovascular
complication was the primary cause of death in 207 (23%) cases. Prediabetes glucose levels were
associated with a 1.7-fold increased mortality risk compared with normoglycemic levels (adjusted odds
ratio (OR) 1.7 and 95% confidence interval (CI) 1.4–2.1; P!0.001). Diabetes glucose levels were
associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3–3.5; P!0.001). In cases
with cardiovascular death, prediabetes glucose levels had a threefold increased cardiovascular
mortality risk (adjusted OR 3.0 and 95% CI 1.7–5.1) and diabetes glucose levels had a fourfold
increased cardiovascular mortality risk (OR 4.0 and 95% CI 1.3–12).
Conclusions: Preoperative hyperglycemia is associated with increased (cardiovascular) mortality in
patients undergoing noncardiac, nonvascular surgery.
European Journal of Endocrinology 156 137–142
Annually, approximately 26 million patients are
scheduled for noncardiac surgery in the United
States (1). Patients undergoing such surgery are at
risk of perioperative cardiac events. In the study of
Lee and colleagues, the incidence of major cardiac
outcome in patients undergoing elective noncardiac
surgery was 1.4%, of which perioperative myo-
cardial infarction (MI) was the most frequent
contributor (2). The incidence of adverse cardiac
events increases in patients at risk of cardiac disease
prior to surgery (3). In this respect, diabetes mellitus
has been associated with adverse cardiac outcome in
noncardiac surgery (2, 4–6).
The prevalence of diabetes continues to increase
worldwide, and is predicted to increase to 300 million
by 2025 (7). Type 2 diabetes is the most prevalent
form and accounts for approximately 90% of patients.
Before the onset of type 2 diabetes, prediabetes
patients exhibit a long asymptomatic period of
increased glucose dysregulation (8). The relationship
between diabetes and cardiovascular disease is
thought to begin early in the progression from normal
glucose tolerance to impaired glucose tolerance to
diabetes (9, 10).
Impaired glucose metabolism is associated with
adverse clinical outcome in the surgical and nonsurgi-
cal population (11–14). However, the relationship
between preoperative glucose levels and perioperative
mortality in noncardiac surgical patients has not
adequately been defined. We hypothesized that pre-
operative hyperglycemia was associated with increased
perioperative mortality in noncardiac, nonvascular
European Journal of Endocrinology (2007) 156 137–142ISSN 0804-4643
q 2007 Society of the European Journal of EndocrinologyDOI: 10.1530/eje.1.02321
Online version via www.eje-online.org
We undertook a retrospective case–control studyamong
75 581 patients above the age of 15 years who
underwent 108 593 noncardiac surgical procedures
between January 1, 1991 and January 1, 2001 in the
Erasmus MC, Rotterdam, The Netherlands. The compu-
terized hospital information system was used to identify
cases and controls. This system holds demographic and
clinical data of all admitted patients, as well as
information on the perioperative course.
Selection of cases and controls
The 2816 patients undergoing vascular surgeryand the
129 patients with an American Society of Anesthesiol-
ogists (ASA) classification 5 (moribund, not expected to
live 24 h irrespective of operation) were excluded.
Candidate case subjects were the 1040 patients from
the remaining population who died of any cause during
surgery or during the hospital stay after surgery within
We intended to select two controls for each case from
the remaining patients. Cases and controls were
matched according to the age (within an interval of
G5 years), gender, calendar year of surgery, and type
of surgery. Surgical procedures were grouped according
to a modified version of the American Heart Associa-
tion/American College of Cardiology (AHA/ACC) classi-
fication (4). For 890 cases, two matching controls could
be selected. For 99 other cases, only one matching
control could be selected, whereas for 51 cases no
matching controls could be selected. As a result, 989
cases were initially matched to 1879 controls. Our
study population consisted of 904 cases and 1247
controls, in which data on preoperative plasma glucose
levels were available.
The computerized hospital database, patient medical
records, nursing reports, surgical reports, anesthetic
reports, and discharge letters were thoroughly analyzed
by our investigators to obtain the following information
on cases and controls; type of surgery, year of surgery,
age, sex, diabetes, hypertension, family history of
coronary artery disease (CAD), smoking, history of
angina pectoris, MI, heart failure, coronary artery
bypass grafting, percutaneous coronary intervention,
cerebrovascular disease, chronic obstructive pulmonary
disease, and renal insufficiency, as well as the ASA
classification and the perioperative use of aspirin, oral
anticoagulant therapy, b-blockers, nitrates, angioten-
sin-converting enzyme inhibitors, angiotensin 2
antagonists, statins, diuretics, prednisone, insulin, and
oral antidiabetic medication.
Preoperative glucose and diabetes status
Patients were classified as having diabetes if their
medical records showed documentation of a previous
history of diabetes, or the use of oral antidiabetes
medication or insulin at the time of hospital admission
before the planned surgical procedure. Preoperative
random glucose levels !5.6 mmol/l (110 mg/dl) were
classified as normal. Impaired glucose levels in the
range of 5.6–11.1 mmol/l were classified as prediabetes
(15). Glucose levels R11.1 mmol/l (200 mg/dl) were
considered diabetes (16).
The hospital information system contains data regard-
ing each patient’s perioperative course. The vital status
at hospital discharge was verified and documented for
each patient. The occurrence of perioperative MI and
clinically apparent strokes were reported. To obtain the
cause of death, two investigators (MDK and DP)
independently reviewed all available perioperative
data, but were blind to preoperative characteristics.
Cardiovascular death was defined as any death with a
cardiovascular complication as the primary or second-
ary cause (according to the definitions of the World
Health Organization), and included deaths following
MI, cardiac arrhythmia, resuscitation, heart failure, or
stroke. Noncardiovascular death was defined as any
death with a principal noncardiovascular cause,
including surgery-related bleeding complications, can-
cer, trauma, and infection. Sudden death in a previously
stable patient was considered as cardiovascular. Events
were counted until hospital discharge or 30 days after
surgery, whichever day came first. We choose 30-day
all-cause mortalityand 30-daycardiovascular mortality
as the endpoints of our study.
Continuous baseline data are described as median
values and corresponding interquartile range (IQR),
and dichotomous data are described as numbers and
percentages. Differences between cases and controls
were analyzed by Wilcoxon’s tests for continuous
variables, and c2tests for dichotomous variables.
We aimed to study to what extent preoperative
glucose levels are associated with perioperative
mortality. For this purpose, uni- and multivariable
logistic regression analyses were applied, with pre-
operative glucose level as main exposure, and age, sex,
type of surgery, a history of diabetes, hypertension,
family history of CAD, smoking, angina pectoris, MI,
heart failure, coronary artery bypass grafting, percuta-
neous coronary intervention, cerebrovascular disease,
and renal insufficiency, ASA classification, and the
perioperative use of aspirin, oral anticoagulant therapy,
b-blockers, nitrates, angiotensin-converting enzyme
P G Noordzij and others
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2007) 156
inhibitors, angiotensin 2 antagonists, statins, diuretics,
and corticosteroids as (potential) confounding factors.
We report crude and adjusted odds ratios (ORs) and
corresponding 95% confidence intervals (CIs). All
statistical tests were two-sided. P!0.05 was considered
Preoperative glucose levels in relation to
Clinical baseline characteristics in cases and controls
are presented in Table 1. Overall preoperative glucose
levels were higher in cases than in controls (median
6.7 mmol/l and IQR 5.3–8.8 vs median 5.7 mmol/l and
IQR 4.8–7.2; P!0.001, Fig. 1). In cases, prediabetes
and diabetes glucose levels were more frequently seen
compared with controls (57 and 13% vs 50 and 5%;
P!0.001; Fig. 2, left panel).
After adjustment for a broad range of potential
confounders, prediabetes glucose levels were associated
with a 1.7-fold increased mortality risk compared with
normoglycemic levels (adjusted OR 1.7 and 95% CI 1.4–
2.1; P!0.001; Table 2). Diabetes glucose levels were
associated with a 2.1-fold increased risk (adjusted OR
2.1 and 95% CI 1.3–3.5; P!0.001).
In subjects with prediabetes glucose levels, a
mortality was observed along with increasing glucose
concentration (Fig. 3). Each 1 mmol/l increase was
associated with a 19% risk increase for mortality
PZ0.002). A similar relationship was not observed
Glucose level (mmol/l)
Cumulative % of patients
Figure 1 Cumulative distribution of glucose levels in cases (bold
line) and controls.
P <0.001P <0.001P <0.001
5.6 11.1 5.6 11.1
All patients No history of DMHistory of DM
Figure 2 Incidence of normal, prediabetes, and diabetes
preoperative glucose levels in cases (black) and controls (grey).
Preoperative random glucose levels !5.6 mmol/l (110 mg/dl) were
classified as normal. Impaired glucose levels in the range of
5.6–11.1 mmol/l were classified as prediabetes. Glucose levels
R11.1 mmol/l (200 mg/dl) were considered diabetes.
Table 1 Baseline characteristics of cases and controls.
No. of patients
Type of surgerya
Low risk (%)
Low–intermediate risk (%)
Intermediate–high risk (%)
Male gender (%)
Medical risk factors
Diabetes mellitus (%)
Family history of coronary
Current smoking (%)
Angina pectoris (%)
Myocardial infarction (%)
Heart failure (%)
Coronary artery bypass
Peripheral vessel disease
64 (48, 74)
65 (51, 75)
aAccording to a modified version of the American Heart Association/Amer-
ican College of Cardiology classification: high risk, aortic; intermediate risk,
abdominal, ear, nose, throat, neurologic, orthopedic, pulmonary, renal
transplant, urologic, vascular, excluding aortic, and carotid; low risk, breast,
carotid, dental, endocrine, eye, gynecology, and reconstructive (4). Note that
we excluded any vascular surgery, as a result we do not have patients in the
Preoperative glucose levels and mortality
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2007) 156
in subjects with diabetes glucose levels (adjusted OR
1.02 and 95% CI 0.91–1.15; PZ0.71).
Preoperative glucose levels and cardiovascular
A cardiovascular complication was the primarycause of
death in 207 (23%) cases. The median glucose level of
these cases was 7.1 mmol/l (IQR 5.3–9.0), significantly
higher than the value in their matching controls (NZ
320; median 5.8 mmol/l and IQR 4.8–7.4; P!0.001).
Prediabetes glucose levels were associated with a
threefold increased cardiovascular mortality risk
compared with normoglycemic levels (adjusted OR 3.0
and 95% CI 1.7–5.1). Diabetes glucose levels were
associated with a fourfold increased cardiovascular
mortality risk (OR 4.0 and 95% CI 1.3–12). Again, in
subjects with prediabetes glucose levels, a continuously
increasing risk of perioperative cardiovascular mortality
was observed along with increasing glucose levels,
however, this relationship did not reach statistical
significance (adjusted OR 1.24 per mmol/l and 95%
CI 0.94–1.64; PZ0.12).
History of diabetes mellitus and diabetes
medication in cases and controls
A history of diabetes mellitus was present in 402
patients (247 cases and 155 controls). Patients with a
history of diabetes had significantly higher glucose
levels than those without such history (median
5.7 mmol/l and IQR 4.8–7.0 vs median 10.5 mmol/l
and IQR 7.8–12.6; P!0.001). In patients without a
history of diabetes, cases were more often classified with
prediabetes glucose levels than controls (60 vs 50%; P!
0.001; Fig. 2, middle panel). In those with a history of
diabetes, the percentage of cases and controls with
prediabetes glucose levels was similar, but cases more
often showed diabetes glucose levels compared with
controls (47 vs 35%; P!0.001; Fig. 2, right panel).
In patients with a history of diabetes, 20% used
insulin, 12% used oral antidiabetes medication, and 2%
used both therapies. The use of any antidiabetes
medication was associated with reduced glucose levels
compared with patients without antidiabetes medi-
cation (median 9.3 mmol/l and IQR 6.3–12.7 vs
median 10.8 mmol/l and IQR 8.3–12.6; PZ0.003).
Insulin was used by 15% of cases vs 33% of controls
(P!0.001), oral antidiabetes medication was used by
6% of cases vs 27% of controls (P!0.001). After
adjustment for a broad range of potential confounders
(Table 2), insulin and oral antidiabetes treatment were
associated with reduced risk of perioperative mortality.
When limited to the 207 cases with cardiovascular
death and their matching controls, insulin therapy
Glucose level (mmol/l)
50 10 15
Figure 3 Relation between glucose level and risk (odds ratio) for
perioperative mortality. Odds ratios are adjusted for history of
diabetes, type of surgery, age, sex, hypertension, family history of
CAD, smoking, angina pectoris, myocardial infarction, heart failure,
coronary artery bypass grafting, percutaneous coronary interven-
tion, cerebrovascular disease, and renal insufficiency, as well as the
ASA classification and the perioperative use of aspirin, oral
anticoagulant therapy, b-blockers, nitrates, angiotensin-converting
enzyme inhibitors, angiotensin 2 antagonists, statins, diuretics, and
corticosteroids. *Odds ratio for perioperative mortality is 1.19 (95%
CI 1.1–1.3) per mmol/l increase of glucose level.
Table 2 Relation between perioperative mortality, preoperative glucose levels, and the use of antidiabetic medication.
Adjusted odds ratio
Normal (!5.6 mmol/l)
Prediabetic (5.6–11.1 mmol/l)
Diabetic (R11.1 mmol/l)
aOdds ratios were adjusted for a history of diabetes, type of surgery, age, sex, hypertension, family history of CAD, smoking, angina pectoris, myocardial
infarction, heart failure, coronary artery bypass grafting, percutaneous coronary intervention, cerebrovascular disease, and renal insufficiency, as well as the
ASA classification and the perioperative use of aspirin, oral anticoagulant therapy, b-blockers, nitrates, angiotensin-converting enzyme inhibitors, angiotensin
2 antagonists, statins, diuretics, and corticosteroids.
bThis analysis is based on 402 patients (247 cases and 155 controls) with a history of diabetes mellitus.
P G Noordzij and others
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2007) 156
(adjusted OR 0.04 and 95% CI 0.01–0.22) as well as
oral antidiabetes medication (adjusted OR 0.04 and
95% CI 0.01–0.26) remained associated with lower
In this case–control study of patients undergoing
noncardiac, nonvascular surgery, elevated preoperative
glucose levels were associated with increased periopera-
tive mortality. Glucose levels in the diabetes range were
associated with a more than twofold all-cause mortality
increase, and a fourfold cardiovascular mortality
increase, compared with normoglycemic levels. Impor-
tantly, glucose levels in the prediabetes range were also
associated with increased risk for both endpoints.
Antidiabetes medication was associated with a
reduction in all-cause mortality as well as cardiovas-
Prediabetes glucose levels in patients without a
history of diabetes were associated with increased
perioperative (cardiovascular) death. This can be
explained by a number of possible mechanisms. First,
the relationship between diabetes and cardiovascular
disease is thought to start early in the progression from
normal glucose tolerance to impaired glucose metab-
olism, and from impaired glucose tolerance to diabetes
(9, 10). As a result of reduced insulin tolerance, and
subsequent hyperglycemia, prediabetes patients may be
at risk for cardiovascular disease. Secondly, patients
with impaired glucose regulation are more frequently
diagnosed with hypertension, obesity, and dyslipidemia,
compared with normoglycemic patients. This cluster of
risk factors, also known as the metabolic syndrome, is
associated with adverse cardiovascular outcome (17).
Perioperative MI is the most frequent fatal cardiovas-
cular complication during noncardiac surgery (2, 3),
however, the pathophysiology underlying perioperative
MI is not completely clear. During surgery, the patient is
exposed to a stress response, which includes a
catecholamine surge with associated hemodynamic
stress, vasospasm, reduced fibrinolytic activity, platelet
activation, and consequent hypercoagulability (18).
This stress state contributes to coronary plaque
instability and rupture in patients with (asymptomatic)
atherosclerotic coronary disease, which leads to
thrombus formation and subsequent vessel occlusion
(18). Impaired glucose metabolism seems to be
associated with increased inflammation of preexistent
atheromatous coronary plaques, resulting in intrapla-
que hemorrhage, and possible plaque rupture leading to
MI (19, 20). In addition, in patients with fixed stenotic
coronary lesions, increased heart rate, and contractility
may induce an oxygen supply and demand mismatch
leading to myocardial ischemia and eventually MI (18).
In patients with a known history of diabetes,
preoperative hyperglycemia was associated with worse
perioperative outcome. Previous studies in patients
undergoing noncardiac surgery have identified a history
of diabetes as a risk factor for perioperative cardiac
events, without taking glucose levels into account (2,
4–6). Stratton and colleagues (21) showed that in
patients with known diabetes, the risk of atherosclerotic
cardiovascular disease increased with increasing
plasma glucose concentration, each 1% increase in
HbA1c level was associated with a 14% increase in the
incidence of fatal and nonfatal MI. In patients with
diabetes undergoing coronary artery bypass graft
surgery, perioperative control of glucose levels was
associated with a reduction in episodes of recurrent
ischemia and an improved survival in the first 2 years
after surgery (23). Oral antidiabetes medication as well
as insulin therapy resulted in a significant reduction of
perioperative mortality. In previous studies, glycemic
control by insulin therapy has been shown to result in
marked improvement in cardiac survival in hypergly-
cemic nondiabetes patients and diabetes patients with
acute coronary syndromes, MI, and those who have
undergone recent cardiac surgery (11, 22, 23). The
switch from free fatty acid myocyte metabolism to
glucose metabolism in ischemic myocardium may be an
important therapeutic intervention during ischemia
(24). However, the protective effect is not entirely clear;
is benefit derived from glycemic control or infused
insulin or both? In our study population, the effect of
oral antidiabetes medication was similar to that of
insulin treatment, and both therapies were associated
with significantly lower preoperative glucose levels in
controls compared with cases.
The results of our study suggest that screening for
glucose dysregulation in surgical patients should be
part of standard preoperative testing. The preoperative
metabolic state, as measured by random blood glucose
measurements, identifies patients at risk for periopera-
tive cardiovascular events. Randomly determined glu-
cose levels have been shown to be an efficient test to
identify patients with prediabetes and undiagnosed
diabetes (15). As it seems to become increasingly clear
that impaired glucose metabolism and the prediabetes
state are associated with adverse clinical outcomes, we
suggest that patients with preoperative glucose levels
above 5.6 mmol/l are further screened for associated
cardiovascular risk factors. In this respect, the type of
surgical procedure, patient clinical characteristics,
further noninvasive test results, and additional medical
therapy may improve perioperative patient manage-
ment (4, 25, 26).
Our study has several limitations that are common
with any case–control study relying on retrospective
data collection. First, information on patient charac-
teristics might have been missed because of observer
bias prejudice. Secondly, multivariable adjustment for
potential confounders is obviously limited to the
available data elements. Unknown, unmeasured con-
founders might still be present. Thirdly, the number of
Preoperative glucose levels and mortality
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2007) 156
patients on oral antidiabetes medication and insulin
therapy was limited and data on perioperative glucose
levels were not available. Therefore, we would like to
emphasize that this early evidence needs confirmation
by adequately powered randomized clinical trials.
This case–control study provides evidence that
preoperative hyperglycemia is associated with increased
1 DeFrances CJ & Hall MJ. 2002 National Hospital Discharge Survey.
Advance Data 2004 342 1–29.
2 Lee TH, MarcantonioER,
Polanczyk CA, Cook EF, Sugarbaker DJ, Donaldson MC, Poss R,
Ho KK, Ludwig LE, Pedan A & Goldman L. Derivation and
prospective validation of a simple index for prediction of cardiac
risk of major noncardiac surgery. Circulation 1999 100 1043–
3 Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K &
Guyatt GH. Perioperative cardiac events in patients undergoing
noncardiac surgery: a reviewof the magnitude of the problem, the
pathophysiology of the events and methods to estimate and
communicate risk. Canadian Medical Association Journal 2005 173
4 Boersma E, Kertai MD, Schouten O, Bax JJ, Noordzij P,
Steyerberg EW, Schinkel AF, van Santen M, Simoons ML,
Thomson IR, Klein J, van Urk H & Poldermans D. Perioperative
cardiovascular mortality in noncardiac surgery: validation of the
Lee cardiac risk index. American Journal of Medicine 2005 118
5 Mangano DT, Browner WS, Hollenberg M, London MJ, Tubau JF &
Tateo IM. Association of perioperative myocardial ischemia with
cardiac morbidity and mortality in men undergoing noncardiac
surgery. The Studyof Perioperative Ischemia Research Group. New
England Journal of Medicine 1990 323 1781–1788.
6 Eagle KA, Berger PB, Calkins H, Chaitman BR, Ewy GA,
Leppo JA, Ryan T, Schlant RC, Winters WL Jr, Gibbons RJ,
Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G,
Jacobs AK, Hiratzka LF, Russell RO & Smith SC Jr. ACC/AHA
guideline update for perioperative cardiovascular evaluation for
noncardiac surgery – executive summarya report of the American
College of Cardiology/American Heart Association Task Force on
Practice Guidelines (Committee to Update the 1996 Guidelines on
Perioperative Cardiovascular Evaluation for Noncardiac Surgery).
Circulation 2002 105 1257–1267.
7 King H, Aubert RE & Herman WH. Global burden of diabetes,
1995–2025. Prevalence, numerical estimates, and projections.
Diabetes Care 1998 21 1414–1431.
8 Deedwania PC & Fonseca VA. Diabetes, prediabetes, and
cardiovascular risk: shifting the paradigm. American Journal of
Medicine 2005 118 939–947.
9 Is the current definition for diabetes relevant to mortality risk from
all causes and cardiovascular and noncardiovascular diseases?
Diabetes Care 2003 26 688–696.
10 Levitan EB, Song Y, Ford ES & Liu S. Is nondiabetic hyperglycemia
a risk factor for cardiovascular disease? A meta-analysis of
prospective studies Archives of Internal Medicine 2004 164
Mangione CM,Thomas EJ,
11 Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H & Apstein CS.
Tight glycemic control in diabetic coronary artery bypass graft
patients improves perioperative outcomes and decreases recurrent
ischemic events. Circulation 2004 109 1497–1502.
12 van den Berghe G, Wouters P, Weekers F, Verwaest C,
Lauwers P & Bouillon R. Intensive insulin therapy in the
critically ill patients. New England Journal of Medicine 2001
13 Van den Berghe G, Wilmer A, Hermans G, Meersseman W,
Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H &
Bouillon R. Intensive insulin therapy in the medical ICU. New
England Journal of Medicine 2006 354 449–461.
14 Kosiborod M, Rathore SS, Inzucchi SE, Masoudi FA, Wang Y,
HavranekEP& KrumholzHM. Admission glucose and mortalityin
elderly patients hospitalized with acute myocardial infarction:
implications for patients with and without recognized diabetes.
Circulation 2005 111 3078–3086.
15 Zhang P, Engelgau MM, Valdez R, Cadwell B, Benjamin SM &
Narayan KM. Efficient cutoff points for three screening tests for
detecting undiagnosed diabetes and pre-diabetes: an economic
analysis. Diabetes Care 2005 28 1321–1325.
16 Report of the expert committee on the diagnosis and classification
of diabetes mellitus. Diabetes Care 2003 26 S5–S20.
17 Nigam A, Bourassa MG, Fortier A, Guertin MC & Tardif JC. The
metabolic syndrome and its components and the long-term risk of
death in patients with coronary heart disease. American Heart
Journal 2006 151 514–521.
18 Libby P, Ridker PM & Maseri A. Inflammation and atherosclerosis.
Circulation 2002 105 1135–1143.
19 Bell DS. Inflammation, insulin resistance, infection, diabetes, and
atherosclerosis. Endocrine Practice 2000 6 272–276.
20 Moreno PR & Fuster V. New aspects in the pathogenesis of diabetic
atherothrombosis. Journal of the American College of Cardiology
2004 44 2293–2300.
21 Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA,
Hadden D, Turner RC & Holman RR. Association of glycaemia
with macrovascular and microvascular complications of type 2
diabetes (UKPDS 35): prospective observational study. British
Medical Journal 2000 321 405–412.
22 Capes SE, Hunt D, Malmberg K & Gerstein HC. Stress
hyperglycaemia and increased risk of death after myocardial
infarction in patients with and without diabetes: a systematic
overview. Lancet 2000 355 773–778.
23 Gerstein HC, Pais P, Pogue J & Yusuf S. Relationship of
glucose and insulin levels to the risk of myocardial infarction:
a case–control study. Journal of the American College of
Cardiology 1999 33 612–619.
24 McNultyPH.Comparisonof local andsystemic effects of insulinon
myocardial glucose extraction in ischemic heart disease. American
Journal of Physiology. Heart and Circulatory Physiology 2000 278
25 Noordzij PG, Boersma E, Bax JJ, Feringa HH, Schreiner F,
Schouten O, Kertai MD, Klein J, van Urk H, Elhendy A &
electrocardiography in patients undergoing noncardiac surgery.
American Journal of Cardiology 2006 97 1103–1106.
26 Boersma E, Poldermans D, Bax JJ, Steyerberg EW, Thomson IR,
Banga JD, van De Ven LL, van Urk H & Roelandt JR. Predictors of
cardiac events after major vascular surgery: role of clinical
characteristics, dobutamine echocardiography, and beta-blocker
therapy. Journal of the American Medical Association 2001 285
Received 6 June 2006
Accepted 31 October 2006
P G Noordzij and others
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2007) 156