EURO PEAN

SO CIETY O F
Original scientific paper CARDIOLOGY ®

European Journal of Preventive

Cardiology

Diabetes: Prevalence, prognosis 2017, Vol. 24(3S) 52–60

! The European Society of
Cardiology 2017
and management of a potent Reprints and permissions:
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cardiovascular risk factor DOI: 10.1177/2047487317709554
journals.sagepub.com/home/ejpc

Anna Norhammar1,2, Linda Mellbin1 and Francesco Cosentino1

Abstract
This review highlights the increased risk of cardiovascular disease and the dismal prognosis after acute coronary events
when diabetes is present. Although there have been improvements in this area, diabetes still confers an increased risk. In
order to achieve successful outcomes in individuals with diabetes, extensive treatment of risk factors and the use of all
available evidence-based therapies are needed. In this context, glucose-lowering therapies and antithrombotic and
revascularisation strategies are detailed in this review. Emerging data indicate that novel glucose-lowering drugs may
impact cardiovascular outcome with mechanisms that are beyond glucose control. In addition, this review addresses
hidden diabetes and impaired glucose tolerance in patients with acute and stable coronary artery disease and how they
influence future cardiovascular risk.

Keywords
Diabetes, abnormal glucose tolerance, acute coronary syndrome, myocardial infarction, glucose control, secondary
prevention, cardiovascular safety, glucose-lowering drugs
Received 8 February 2017; accepted 22 April 2017

Prevalence of abnormal glucose tolerance tests (OGTTs) in acute myocardial infarction

regulation
The prevalence of previously known diabetes among
patients with acute coronary syndromes (ACS) has
increased the later decades parallel to the increase in
diabetes prevalence seen in the general population
and due to the improved life-expectancy in diabetes
individuals.1,2 The prevalence varies between 20%
and 30%, with lower proportions in the Scandinavian
countries and higher proportions among Central and
Eastern European countries and in the USA.3–5 By con-
trast, in clinical randomised trials, the prevalence of
patients with diabetes tends to be lower because of
inclusion/exclusion criteria that often exclude the
most severely compromised patients. Hyperglycaemia
is often present in patients with ACS and was already
described in 1929 by Levine, who reported high levels
of glucose in the urine of patients with acute coronary
thrombosis. For a long time, this finding was mainly
attributed to the stressful situation caused by an acute
event.6 However, more recent studies with repeated glu-
cose evaluations by means of standardised oral glucose
(AMI) and in stable coronary artery disease (CAD)
populations demonstrated that undiagnosed diabetes
and impaired glucose tolerance (subsequently named
together as abnormal glucose tolerance [AGT]) are
common, persist over time and likely precede the
event. Approximately 60–65% of CAD patients present
with AGT when screened with an OGTT, while a large
part of them would remain undiagnosed if HbA1c
or fasting plasma glucose (FPG) were used as screening
tools.7–11 The latest joint guidelines from the European
Society of Cardiology (ESC) and the European Study
of Diabetes (EASD) recommend that screening for
potential type 2 diabetes mellitus in people with cardio-
vascular disease (CVD) is initiated with HbA1c and
1
Cardiology Unit, Department of Medicine Solna, Karolinska University
Hospital, Stockholm, Sweden
2
Capio S:t Görans hospital, Sankt Göransplan, Stockholm, Sweden
Corresponding author:
Francesco Cosentino, Cardiology Unit, S1:02 Department of Medicine
Solna, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Email: francesco.cosentino@ki.se
Norhammar et al.
FPG, and that an OGTT should be added if HbA1c and
FPG are inconclusive (Figure 1).11 It is of importance
not to perform an OGTT too early in the course of an
AMI, but to wait 4–5 days after an acute event in order
to minimise the influence of stress.8,11
Prognosis after ACS in the presence
of abnormal glucose regulation
Diabetes has for a long time been a recognised risk
factor for AMI. In the 1970s, the Framingham Study
showed that diabetes conferred a two- to four-times
greater risk for MI and a four- to six-times greater
risk for heart failure.12 The INTERHEART study con-
firmed this two- to four-times greater risk for MI on a
global scale.13 Parallel to the emerging overall decrease
in MI and cardiovascular (CV) mortality in the
Western world, there seems to have also been a reduc-
tion in the MI risk associated with diabetes (of one- to
two-times), although with a greater impact on younger
ages and a lesser impact on older ages.14–16
National reports and registry studies show impres-
sive reductions in mortality after AMI in patients both
with and without diabetes, but there is still a significant
gap between these two populations (Figure 2).3,17 Such
a reduction in mortality rate is due to an increased
implementation of secondary prevention measures, as
Cardiovasular disease (CVD) and Diabetes mellitus (DM)
Main diagnosis
DM ± CVD
CVD unknown CVD unknown
ECG ECG
Echocardiography Echocardiography
Exercise test Exercise test
Holter monitoring Holter monitoring
if positive–cardiology
consultation
Normal Abnormal
Follow-up Cardiology consultation
Ischaemia treatment
Non-invasive or invasive
Figure 1. Algorithm on how to screen for diabetes and abnormal glucose regulation in patients with coronary artery disease.11
Printed with permission from Oxford University Press.
ACS: acute coronary syndrome; ECG: electrocardiography; FPG: fasting plasma glucose; IGT: Impaired glucose tolerance; MI: myo-
cardial infarction; OCTT: oral glucose tolerance test.
53
well as revascularisation of the acute coronary occlu-
sion.3,11,18 However, there are signals that we are far
from an optimal use of state-of-the-art treatment stra-
tegies in patients with diabetes.3,11,19,20 The under-use
of evidence-based therapies in diabetic patients with
ACS could be related to a different clinical presenta-
tion, with silent ischaemia, more diffuse symptoms or
symptoms mixed with hypoglycaemia resulting in late
admission for/diagnosis of AMI. Another factor could
be a form of physician-related hesitancy to utilise inten-
sive treatment because of the increased vulnerability of
patients when diabetes is present. However, it is estab-
lished that therapeutic strategies including b-blockers,
statins, antithrombotic therapies and early revascular-
isation in the setting of an AMI are effective in patients
both with and without diabetes, and the prognosis is
much more severe if evidence-based therapies are with-
held.3,11,21,22 The most recent recommendations on how
to prevent CV complications in diabetic individuals are
summarised in Figure 3.21 In diabetes, the choice and
impact of glucose-lowering and antithrombotic thera-
pies as well as revascularisation strategies after ACS are
of importance, and these are extensively discussed
below. Since patients with diabetes today survive
AMIs to a much greater extent, there will be a higher
number of diabetic individuals with chronic ischaemic
heart disease. In unselected registry populations,
Main diagnosis
CVD ± DM
DM unknown DM unknown
HbAIc, FPG, Screen for
if needed OGTT microangiopathy
Blood lipids if poor glycaemic
if MI or ACS aim for control
reasonable glycaemic Diabetology consultation
control
Normal Newly detected.
Follow-up DM or IGT
Diabetology consultation
54
Proportion (%)
35
30
25
20
15
10
0
1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014
DM
Figure 2. Improved 1-year survival after myocardial infarction in Sweden, 1994–2014 (annual report Swedeheart 2015 available at
www.swedeheart.se). Published with permission from Swedeheart.
DM: diabetes mellitus.
diabetes confers a successively increasing risk for CV
complications beyond the first year after the acute
event. Common complications, apart from increased
long-term mortality, are hospitalisation for heart fail-
ure and re-infarction.23 This risk is more pronounced in
the presence of insulin therapy and long-standing dia-
betes.14,21,22,23 Long-term follow-up studies of CV com-
plications in CAD patients with glucose abnormalities
are now being reported.24,25 A small cohort study
found that newly discovered AGT in the presence of
established CAD predicts CV mortality and morbidity
(Figure 4).24 This indicates that an OGTT after an AMI
may be useful for identifying individuals at increased
CV risk rather than for diagnosing diabetes. According
to the most recent guidelines, when these individuals
are identified, secondary prevention and lifestyle
changes should be implemented.21
Glucose control in acute and stable CAD
In the setting of ACS, elevated plasma glucose or
HbA1c are associated with worse prognosis.11,26 The
hypothesis that glucose lowering in this setting would
improve prognosis was tested in the randomised
Diabetes and Insulin–Glucose Infusion in Acute
Myocardial Infarction (DIGAMI) trial.26 A total of
620 patients were randomised to intensified insulin-
based glycaemic control including 24-hour insulin–glu-
cose infusion (with the aim of stabilising blood glucose
European Journal of Preventive Cardiology 24(3S)
Non-DM
at between 7 and 10.9 mmol/L) followed by multi-dose
insulin or standard glucose lowering. After 3.4 years, an
11% absolute risk reduction in mortality was
obtained.26 These positive results were not confirmed
in the DIGAMI 2 trial.27 One reason for the discrepant
results between DIGAMI 1 and DIGAMI 2 is the lack
of difference in glucose levels between the intensified
insulin-based group and the control group achieved in
the latter trial. Another explanation is that blood glu-
cose and HbA1c at admission were substantially higher
in DIGAMI 1 as compared to DIGAMI 2 (mean blood
glucose 15.4 vs. 12.8 mmol/L and HbA1c 8.2% vs.
7.2%, respectively). Moreover, the overall mortality
rate was lower in DIGAMI 2 due to more extensive
treatment with evidence-based therapies, such as statins
and revascularisation. In the acute setting, insulin has
been studied not only for improving glucose levels, but
also for stopping the myocardial metabolic vicious
circle that is triggered during an ischaemic event.28
However, randomised trials using a glucose–insulin–
potassium (GIK) infusion, glucose–insulin or only insu-
lin have not shown consistent mortality or morbidity
reductions, as thoroughly reviewed by Kloner and
Nesto.29 Possible explanations for these negative results
are volume overload caused by the GIK infusion,
increases in glucose levels or late administration of
the insulin infusion when negative metabolic effects
were already established.28,29 Current ESC guidelines
recommend (class IIa, level of evidence C) that
Norhammar et al. 55

Recommendations for management of diabetes

Recommendations Class a Level b Ref c

Lifestyle changes including smoking cessation, low fat diet, high fibre diet, aerobic physical activity, and
strength training are recommended. I A 387

Reduction in energy intake is recommended to patients to help achieve lower weight or prevent weight gain. I B 387

A target HbAIc for the reduction in risk of CVD and microvascular complications in DM of <7.0% (<53 mmol/mol) is
recommended for the majority of non-pregnant adults with either type I or type 2 DM. I A 388,389

For patients with a long duration of DM, the elderly, frail, or those with existing CVD, a relaxing of the HbAIc targets
(i.e. less stringent) should be considered. IIa B 389

A target HbAIc of ≤6.5% (≤48 mmol/mol) should be considered at diagnosis or early in the course of type 2 DM in patients,
IIa B 389
who are not frail and do not have CVD.

When screening for DM in individuals with or without CVD, assessment of HbAIc (which can be done non-fasting) or fasting
blood glucose should be considered. An oral glucose tolernce test can be offered when there is still doubt. IIa A 390

Metformin is recommended as first-line therapy, if tolerated and not contra-indicated, following evaluation of renal function. I B 391

Avoidance of hypoglycaemia and excessive weight gain should be considered and individual approaches (with respect to 389,392,
IIa B
both treatment targets and drug choices) should be considered in patients with advanced disease. 393

In patients with type 2 DM and CVD, the use of an SGLT2 inhibitor should be considered early in the course of the disease
IIa B 394
to reduce CV and total mortality.

Lipid lowering agents (prinicipally statins) are recommended to reduce CV risk in all patients with type 2 or type I DM above
the age of 40 years. I A 371, 372

Lipid lowering agents (prinicipally statins) may be considered also in individuals below 40 years of age if at significantly
elevated risk, based on the presence of micro-vascular complications or of multiple CV risk factors. IIb A 371, 372

In DM patients at very high-risk (see table 5), a LDL-C target <1.8 mmol/L (<70 mg/dL), or a reduction of at least 50% if the
baseline LDL-C is between 1.8 and 3.5 mmol/L(70 and 135 mg/dL), is recommended.d
In DM patients with high-risk (see table 5), LDL-C target <2.6 mmol/L (<100 mg/dL), or a reduction of at least 50% if the I B 395
baseline LDL-C is between 2.6 and 5.1 mmol/L(100 and 200 mg/dL) is recommended.d

BP targets in type 2 DM are generally recommended to be < 140/85 mmHg, but a lower target of < 130/80 mmHg is
recommended in selected patients (e.g. younger patients at elevated risk for specific complications) for additional gains on
stroke, retinopathy and albuminuria risk. Renin-angiotensin-aldosterone system blocker is recommended in the treatment of I B 396,397
hypertension in DM, particularly in the presence of proteinuria or micro-albuminuria. Recommended BP target in patients
with type 1 DM is < 130/1/80 mmHg.

The use of drugs that increase HDL-C to prevent CVD in type 2 DM is not recommended. III A 386

Antiplatelet therapy (e.g. with aspirin) is not recommended for people with DM who do not have CVD. III A 398

Figure 3. Summary of recommendations for cardiovascular disease prevention in diabetic individuals from the European Society of
Cardiology guidelines on cardiovascular disease prevention 2016.21 Printed with permission from Oxford University Press.
BP: blood pressure; CV: cardiovascular; CVD: cardiovascular disease; DM: diabetes mellitus; HDL-C: high-density lipoprotein chol-
esterol; LDL-C: low-density lipoprotein cholesterol; SGLT2: sodium glucose cotransporter 2.

insulin-based glycaemic control should be considered
only in ACS patients with significant hyperglycaemia
(>10 mmol/L or >180 mg/dL), with awareness of the
increased risk of hypoglycaemia in patients with comor-
bidities such as malnutrition and renal insufficiency.11
In stable CAD, the recommended glycaemic target is
HbA1c 7% (53 mmol/mol), but an individualised
treatment is emphasised by most recent guide-
lines.11,21,22 Accordingly, in elderly patients, in those
with long-standing diabetes or in those with established
CVD, intensive glucose lowering may even be harm-
ful.30 The target is therefore less strict (<7.5–8.0%
[<58–64 mmol/mol]). Several glucose-lowering drugs
are available. First-line treatment consists of lifestyle
interventions and metformin.11 Sulfonylureas and
insulin have traditionally been used as second-line
treatments. Both of these drugs have the disadvantage
of being associated with an increased risk of severe
hypoglycaemia, which may contribute to cardiac com-
plications and arrhythmia.11,30,31 Novel classes of glu-
cose-lowering agents such as dipeptidyl peptidase-4
(DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1)
agonists and sodium glucose cotransporter 2 (SGLT2)
inhibitors are emerging as second-line options.21,22
Recent trials with DPP-4 inhibitors in patients with
diabetes and established CVD have demonstrated
56
1.0
0.9
0.8
Event free proportion
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 1
No. at risk
patients
Normal 54
AGT 113
Figure 4. 10-year follow-up of the GAMI cohort. Time to combined event (cardiovascular mortality/new acute myocardial infarc-
tion/stroke/hospitalisation for heart failure) after myocardial infarction in those with (red) and without (blue) newly detected AGT by
oral glucose tolerance test at discharge.24
AGT: abnormal glucose tolerance; GAMI: Glucose Tolerance in Patients with Acute Myocardial Infarction.
non-inferiority but not superiority with respect to CV
risk; there was, however, an increased rate of hospital-
isation with saxagliptin.21,22 There has been a very
recent paradigm shift, with last-generation glucose-
lowering agents showing significant reductions in CV
events in outcome trials/ In the Empagliflozin
Cardiovascular Outcome Event Trial in Type 2
Diabetes Mellitus Patients (EMPA-REG) outcome
trial, the SGLT2 inhibitor empagliflozin reduced
CVD death, all-cause mortality and hospitalisation
for heart failure; in the LEADER trial, the GLP-1
receptor agonist liraglutide reduced CV death and all-
cause mortality; and finally, in the trial to evalutate
cardiovascular and other long-term outcomes with
semaglutide in subjects with Type 2 Diabetes (the
SUSTAIN-6 trial), the long-acting GLP-1 inhibitor
semaglutide reduced CV events. These positive results
seem to be related to mechanisms beyond the glucose-
lowering effect, and more research is needed in order to
understand these trial results.
Antithrombotic therapy
Although platelet reactivity is a major feature in
patients with diabetes, the benefits of aspirin in diabetes
subjects without established CVD remain inconclu-
sive.32 In order to better determine whether aspirin
plays any beneficial role in the primary prevention of
European Journal of Preventive Cardiology 24(3S)
Log-rank p = 0.0018
2 3 4 5 6 7 8 9 10 11 12 13
Years
52 50 48 45 43 40
84 80 76 68 60 55
CVD in diabetes, the ongoing A Study of
Cardiovascular Events in Diabetes (ASCEND) trial
has enrolled over 15,000 patients with plans to com-
plete the study within the next couple of years.
Additionally, the Aspirin and Simvastatin
Combination for Cardiovascular Events Prevention
Trial in Diabetes (ACCEPT-D) trial has a planned
enrolment of 5170 patients, evaluating the benefit of
aspirin plus statin versus statin alone. These trials
should help to define the risk–benefit ratio of low-
dose aspirin in this setting. In secondary prevention,
aspirin treatment is similarly effective in patients with
and without diabetes mellitus. Data from the
Antiplatelet Trialists’ Collaboration on more than
45,000 diabetes patients showed that antiplatelet ther-
apy reduces major CV events by 25%.33 Hence, the use
of aspirin is highly recommended in diabetes patients
with a history of CVD.11 The P2Y12 receptor plays a
central role in platelet aggregation. Blockade of this
receptor represents a valid strategy for preventing
atherothrombotic complications in diabetes.11,34 In
the diabetes subgroup of the clopidogrel versus aspirin
in patients at risk of ischaemic events (CAPRIE) trial,
in which patients with CAD, cerebrovascular disease or
peripheral artery disease were randomised to aspirin or
clopidogrel, an absolute risk reduction was observed
that was significantly larger than in subjects without
diabetes.11,34 However, in the Clopidogrel for High
Norhammar et al.
Atherothrombotic Risk and Ischemic Stabilization,
Management, and Avoidance (CHARISMA) trial, the
addition of clopidogrel to aspirin did not demonstrate
any further benefit than aspirin alone in the prevention
of CV outcomes.11,34 On the other hand, the CURE
trial demonstrated the benefit of a reduction in athero-
thrombotic events with the addition of clopidogrel to
aspirin after ACS in those both with and without dia-
betes.11,34 The P2Y12 inhibitors prasugrel (irreversible)
and ticagrelor (reversible) have been shown to be highly
effective in diabetes patients with ACS, and may be
preferred to clopidogrel in patients with ACS undergo-
ing percutaneous coronary intervention (PCI). Indeed,
in the Trial to Assess Improvement in Therapeutic
Outcomes by Optimizing Platelet Inhibition with
Prasugrel-Thrombolysis In Myocardial Infarction 38
(TRITON-TIMI 38) study, diabetes subjects tended
to have a greater reduction in ischaemic events without
an observed increase in major bleeding.34 These data
demonstrate that the more intensive oral antiplatelet
therapy provided with prasugrel is of particular benefit
to patients with diabetes. In the Platelet Inhibition and
Patient Outcomes (PLATO) trial, ticagrelor equally
reduced the rate of ischaemic events in ACS patients
both with and without diabetes.35 Most recent guide-
lines suggest that the Dual antiplatelet treatment
(DAPT) should be continued for up to at least 12
months, but a longer duration is under investigation.34
The use of glycoprotein (GP) IIb/IIIa inhibitors is not
supported by current evidence, except for in high-risk
patients.35 In diabetic patients, trials performed with-
out concomitant use of thienopyridines have been
shown to have a favourable impact on outcomes.34
Since a high clopidogrel loading dose was not present
in the design of these studies, the data obtained remain
questionable. The early eptifibatide therapy in non-ST-
segment elevation acute coronary syndrome (EARLY-
ACS) trial showed that administration of eptifibatide
before angiography in non-ST-elevation myocardial
infarction (NSTEMI) was not superior to its use after
PCI.34 Furthermore, the early use of eptifibatide was
associated with an increased risk of non-life-threatening
bleeding. However, the efficacy of GP IIb/IIIa inhibi-
tors correlates with the severity of the ACS, and the
risk–benefit ratio should always be assessed in an indi-
vidualised manner.34 Accordingly, the iNtracoronary
Stenting and Antithrombotic Regimen: Rapid Early
Action for Coronary Treatment (ISAR-REACT) 5
trial demonstrated that abciximab compared to placebo
after pre-treatment with clopidogrel reduces adverse
events in patients with high-risk ACS undergoing
PCI.11,34 Therefore, diabetes patients with NSTEMI
and high troponin release should be treated with GP
IIb/IIIa inhibitors, if the bleeding risk is acceptable. In
STEMI patients, the benefits of GP IIb/IIIa inhibitors
57
are controversial, and there are conflicting results in
diabetes. A meta-analysis of 16 randomised trials
showed that GP IIb/IIIa inhibitors did not reduce 30-
day mortality or re-infarction, but were associated with
a higher risk of major bleeding complications.11
Mortality was reduced in high-risk ACS, but not re-
infarction. In contrast, the Controlled Abciximab and
Device Investigation to Lower Late Angioplasty
Complications (CADILLAC) trial conducted in low-
risk ACS patients with diabetes did not show any bene-
fit with the use of abciximab after balloon angioplasty
or stenting.11
Anticoagulants
The available evidence indicates that anticoagulation is
effective in addition to platelet inhibition and that the
combination of the two is more effective than either
treatment alone.34 Fondaparinux, an indirect factor
Xa inhibitor, has been shown to be non-inferior to
low-weight molecular heparin (LWMH) at reducing
the risk of ischaemic events. The he Pentasaccharide in
Unstable Angina (PENTUA) and the Organization for
the Assessment of Strategies for Ischemic Syndromes 6
(OASIS-6) trials have demonstrated that the major
advantage of fondaparinux is the low risk of major
bleeding with a consistent reduction of short- and
long-term morbidity and mortality.34 An analysis
exploring the uptake of fondaparinux compared with
LMWH among 40616 NSTEMI patients from a large-
scale Scandinavian registry reported fewer in-hospital
mortality and bleeding events associated with the use
of fondaparinux, while the reductions of CV mortality
at 30 and 180 days were comparable in the two groups.35
Overall, fondaparinux is considered to be the parenteral
anticoagulant with the most favourable
efficacy–safety profile and is now recommended as a
first-line anticoagulant in ACS patients.34 In a diabetes
subgroup analysis of the Acute Catheterization and
Urgent Intervention Triage strategy (ACUITY) trial,
monotherapy with the direct thrombin inhibitor bivalir-
udin was associated with similar rates of death, MI or
unplanned ischaemic revascularisation compared with
GP IIb/IIIa plus heparin, but with a lower rate of
major bleeding. These findings are of importance since
diabetes per se is a predictor of bleeding complications in
patients with ACS undergoing PCI.34 In conclusion,
fondaparinux and bivalirudin might be preferred in dia-
betic patients due to the lower risk of bleeding
complications.
Revascularisation
An important part of the secondary preventive pro-
gramme in patients with diabetes includes the
58
revascularisation of affected coronary arteries if there
are signs of myocardial ischaemia.36 An early revascu-
larisation strategy improved survival after hospitalisa-
tion for unstable angina and reduced re-infarctions in
diabetic individuals in the Fragmin and Fast
Revascularization During Instability in Coronary
Artery Disease (FRISC) 2 trial, which was conducted
before the stents era. Registries indicate a tendency
towards underuse of revascularisation among patients
with diabetes and established ischaemic heart disease,
who more often have no recorded revascularisation
procedure than those without diabetes.20,23 The prefer-
ence of the patient, a complex CAD configuration and
no remaining signs of myocardial ischaemia could also
interfere with this. Whatever the reasons, an increased
awareness of the problem is needed, since prognosis
might be influenced.20,36 The guidelines state that
choice of revascularisation strategy (PCI or coronary
artery bypass grafting [CABG]) should be implemented
after a risk–benefit evaluation of a multidisciplinary
heart team.11,36
CAD is often more extensive and diffuse if diabetes
is present,4,11,35,36 with an increased tendency to resten-
osis, stent thrombosis and graft occlusion, especially in
those treated with insulin.11,23,34,36 The introduction of
mammary artery grafts, bare-metal stents (BMSs) and
drug-eluting stents (DESs) has, however, improved
patency after revascularisation in those with diabetes.
The use of DESs instead of BMSs further lowers the
restenosis rate in diabetes.37 The SYNergy between per-
cutaneous coronary intervention with TAXus and car-
diac surgery (SYNTAX) trial and the Future
Revascularization Evaluation in Patients with
Diabetes Mellitus: Optimal Management of
Multivessel Disease (FREEDOM) trial suggest a pref-
erence for CABG over PCI in patients with diabetes
and multivessel disease due to the lower rate of major
CV events and improved long-term mortality with
CABG in this setting.38,39 The choice of PCI with a
DES can, however, be considered in less extensive
CAD and when the SYNTAX score is low.11,39 In
everyday practise, the configuration of the coronary
artery stenosis may be difficult to target with revascu-
larisation. In this setting, intense secondary prevention
is strongly recommended. In patients with depressed
left systolic ventricular function due to two- or three-
vessel CAD, there are indications based on the recent
long-term follow-up of the Surgical Treatment for
Ischemic Heart Failure (STICH) trial that prognosis
might be improved by revascularisation with CABG.
Since the evidence is sparse, the most recent guidelines
on revascularisation state that the assessment of viabil-
ity should not be the sole factor when deciding on the
best strategy for patients with severe left ventricular
function and evident CAD.39
European Journal of Preventive Cardiology 24(3S)
Lifestyle intervention
In recent years, several guidelines on diabetes and on
CVD have stressed the importance of addressing life-
style habits in high-risk individuals.21,22 The most
important changes to be implemented are smoking ces-
sation, increased physical activity and healthy diet pat-
terns, and avoid alcohol over consumption.
Furthermore, psychosocial risk factors should be
explored, as they might interfere with the possibility
of succeeding with lifestyle changes. Small changes in
body weight can indeed improve glucose control. Short
intervals from long-term sitting (‘brakers’), with two
minutes of standing/walking every 20 minutes, have
been shown to improve glucose and insulin levels.
Figure 3 reviews important lifestyle interventions in
diabetes. Mainly, a Mediterranean diet pattern includ-
ing fruits, vegetables, legumes, olive oil and fish is advo-
cated. Patients with type 2 diabetes obtain a great
benefit by limiting saturated and trans fats and alcohol
intake, monitoring carbohydrate consumption and
increasing dietary fibre. In the the PREvención con
DIeta MEDiterránea (PREDIMED) study, which
investigated individuals at high CV risk, including
40% with diabetes, a Mediterranean diet pattern and
extra portions of olive oil or nuts reduced CV events,
mortality and the development of diabetes.21 In the
Steno 2 trial, CV complications and mortality were
reduced in type 2 diabetes patients with multifactorial
treatment, including lifestyle changes.18
Conclusion
In recent decades, type 2 diabetes patients have
achieved longer life expectancy, better outcomes after
myocardial infarction and a reduction in CV mortality.
This depends on CV prevention, multifactorial treat-
ment and improved management of acute and stable
CAD. However, CVD remains the most common
cause of mortality, and complications such as heart
failure are increasingly common in this
setting. Further research and intensive management are
mandatory in order to prevent diabetes develop-
ment and the risk of CV complications in patients
with established type 2 diabetes.
Author contribution
AN, LM and FC drafted and critically revised the manu-
script. All gave final approval and agree to be accountable
for all aspects of work, ensuing integrity and accuracy.
Declaration of conflicting interests
The author(s) declared the following potential conflicts of
interest with respect to the research, authorship, and/or pub-
lication of this article: FC declares speaker and advisory
Norhammar et al.
boards honorarium from Astra Zeneca, Bristol Myers
Squibb, Merck Sharp & Dohme, Roche, Abbott, Bayer,
Novo Nordisk; AN declare speaker’s fee and advisory
boards honorarium from MSD Sweden, Ely Lilly, Novo
Nordisk, Boehringer Ingelheim and Astra Zeneca; LM
declares from speaker’s fee and advisory boards honorarium
from MSD, Sanofi, Boehringer Ingelheim and Novo Nordisk.
Funding
The author(s) disclosed receipt of the following financial sup-
port for the research, authorship, and/or publication of this
article: This paper was supported by grants from
VetenskaprÍdet (No. 2016-02706), Swedish Heart-Lung
Foundation (201440360) and Konung Gustav:Vs och
Drottning Victorias Frimurarestiftelse (to FC); from
Swedish Heart-Lung Foundation (to AN) and Swedish
Heart-Lung Foundation and Research grants from Bayer
AG (to LM).
References
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