Definitions for the recommendation classes (I, II, IIa, IIb III) and levels of evidence (A, B, C) are given at the end of the "Major Recommendations."
Definition, Classification, and Screening of Diabetes and Pre-diabetic Glucose Abnormalities
Definition and Classification of Diabetes
The definition and diagnostic classification of diabetes and its pre-states should be based on the level of the subsequent risk of cardiovascular complications. Class I, Level of Evidence B.
Screening for Undiagnosed Diabetes
Early stages of hyperglycaemia and asymptomatic type 2 diabetes are best diagnosed by an oral glucose tolerance test (OGTT) that gives both fasting and two-hours post-load glucose (2-hPG) values. Class I, Level of Evidence B.
Detection for People at High Risk for Diabetes
Primary screening for the potential type 2 diabetes can be done most efficiently using a non-invasive risk score, subsequently combined with a diagnostic oral glucose tolerance testing in people with high score values. Class I, level of Evidence A.
Epidemiology of Diabetes, Impaired Glucose Homeostasis (IGH), and Cardiovascular Risk
Diabetes and Coronary Artery Disease (CAD)
The relationship between hyperglycaemia and cardiovascular disease (CVD) is to be seen as a continuum. For each 1% increase of glycated haemoglobin (HbA1C), there is a defined increased risk for CVD. Class I, Level of Evidence A.
The risk of CVD for people with overt diabetes is increased by two to three times for men and three to five times for women compared to people without diabetes. Class I, Level A.
IGH and CAD
Cardiovascular Risk and Post-Prandial Hyperglycaemia
Information on post-prandial (post-load) glucose provides better information about the future risk for CVD than fasting glucose, and elevated post-prandial glucose also predicts the cardiovascular risk in subjects with normal fasting glucose levels. Class I, Level of Evidence A.
Glycaemic Control and Cardiovascular Risk
Improved control of post-prandial glycaemia may lower cardiovascular risk and mortality.
Class IIb, Level of Evidence C.
Gender Differences in CAD Related to Diabetes
Glucometabolic perturbations carry a particularly high risk for cardiovascular morbidity and mortality in women, who in this respect need special medical attention. Class IIa, Level of Evidence B.
Glucose Homeostasis and Cerebrovascular Disease
People with diabetes and impaired glucose tolerance (IGT) have an increased risk for stroke. Class I, Level of Evidence A.
In stroke patients, unrecognized hyperglycaemia is mostly high post-load glucose seen in the OGTT, whereas the measurement of fasting glucose is insensitive in detecting unrecognized hyperglycaemia. Class I, Level of Evidence B.
Identification of Subjects at High Risk for CVD or Diabetes
The Metabolic Syndrome
The metabolic syndrome identifies people at a higher risk of CVD than that in the general population, although it may not provide a better or even equally good prediction of cardiovascular risk than scores based on the major cardiovascular risk factors (age, blood pressure, smoking, and serum cholesterol). Class II, Level of Evidence B.
Risk Charts
Several cardiovascular risk assessment tools exist and they can be applied to both non-diabetic and diabetic subjects. Class I, level of Evidence A.
An assessment of predicted type 2 diabetes risk should be part of the routine health care using the risk assessment tools available. Class II, Level of Evidence A.
Patients without known diabetes but with established CVD should be investigated with an OGTT. Class I, Level of Evidence B.
Preventing Progression to Diabetes
People at high risk for type 2 diabetes should receive appropriate life style counselling and if needed pharmacological therapy to reduce or delay their risk of developing diabetes. This may also decrease their risk of CVD. Class I, Level of Evidence A.
In people with IGT, the onset of diabetes can be delayed by certain drugs (such as metformin, acarbose and rosiglitazone). Class I, Level of Evidence A.
Prevention of CVD by Physical Activity
Diabetic patients should be advised to be physically active in order to decrease their cardiovascular risk. Class I, Level of Evidence A.
Treatment to Reduce Cardiovascular Risk
Life Style and Comprehensive Management
Structured patient education improves metabolic and blood pressure control. Class I, Level of Evidence A.
Non-pharmacological life style therapy improves metabolic control. Class I, Level of Evidence A.
Self-monitoring improves glycaemic control. Class I, Level of Evidence A.
Glycaemic Control
Near normoglycaemic control reduces microvascular complications. Class I, Level of Evidence A.
Near normoglycaemia reduces macrovascular complications. Class I, Level of Evidence A.
Intensified insulin therapy in type 1 diabetes improves morbidity and mortality. Class I, Level of Evidence A.
Early, stepwise increase of therapy towards pre-defined treatment targets improves a composite of morbidity and mortality in type 2 diabetes. Class IIa, Level of Evidence B.
Early initiation of insulin should be considered in patients with type 2 diabetes failing glucose target, and in patients with excessive post-prandial glucose excursions. Meal-time short-acting insulin is recommended. Class IIb, Level of Evidence C.
Metformin is recommended as first line drug in overweight type 2 diabetes. Class IIb, Level of Evidence C.
Dyslipidaemia
Secondary Prevention
Elevated low-density lipoprotein (LDL)- and low high-density lipoprotein (HDL)-cholesterol are important risk factors in people with diabetes. Class I, Level of Evidence A.
Statins are first-line agents for lowering LDL-cholesterol in diabetic patients. Class I, Level of Evidence A.
In diabetic patients with CVD, statin therapy should be initiated regardless of baseline LDL-cholesterol with a treatment target of <1.8 mmol/L. Class I, Level of Evidence B.
Primary Prevention
Statin therapy should be considered in adult patients with type 2 diabetes, without CVD, if total cholesterol >3.5 mmol/L (>135 mg/dL), with treatment aiming for an LDL-cholesterol reduction of 30 to 40%. Class IIb, Level of Evidence B.
Given the high lifetime risk of CVD, it is suggested that all type 1 patients over the age of 40 years should be considered for statin therapy. In patients 18 to 39 years (either type 1 or type 2), statin therapy should be considered when other risk factors are present, e.g., nephropathy, poor glycaemic control, retinopathy, hypertension, hypercholesterolaemia, features of the metabolic syndrome, or family history of premature vascular disease. Class IIb, Level of Evidence C.
Guidelines for HDL Cholesterol and Triglycerides
In diabetic patients with hypertriglyceridaemia >2 mmol/L (177 mg/dL) remaining after having reached the LDL-cholesterol target, it is recommended that statin therapy should be increased to reduce non-HDL cholesterol with a goal of therapy 0.8 mmol/L (31 mg/dL) higher than that identified for LDL. In patients on maximum dose, or maximum tolerated dose of statin, where LDL-C or non-HDL-C is not to goal, the addition of ezetimibe, a specific inhibitor of cholesterol absorption, should provide effective further cholesterol reduction. In some cases combination therapy with nicotinic acid or fibrates may be considered. Class IIb, level of Evidence B.
Blood Pressure
In patients with diabetes and hypertension, the recommended target for blood pressure control is <130/80 mm Hg. Class I, Level of Evidence B.
The cardiovascular risk in patients with diabetes and hypertension is substantially enhanced. The risk can be effectively reduced by blood pressure-lowering treatment. Class I, Level of Evidence A.
The diabetic patient usually requires a combination of several anti-hypertensive drugs for satisfactory blood pressure control. Class I, Level of Evidence A.
The diabetic patient should be prescribed a renin-angiotensin system (RAS) inhibitor as part of the blood pressure-lowering treatment. Class I, Level of Evidence A.
Screening for microalbuminuria and adequate blood pressure-lowering therapy including the use of angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor-II-blockers, improves micro- and macrovascular morbidity in type 1 and type 2 diabetes. Class I, Level of Evidence A.
Management of CVD
Treatment Principles
Risk Stratification
Early risk stratification should be part of the evaluation of the diabetic patient after acute coronary syndromes (ACS). Class IIa, Level of Evidence C.
Treatment Targets
Treatment targets, as listed in the table below, should be outlined and applied in each diabetic patient following an ACS. Class IIa, Level of Evidence C.
| Table. Recommended Treatment Targets for Patients with Diabetes and CAD (adapted after the European Guidelines for Cardiovascular Disease Prevention) |
|
Blood pressure (systolic/diastolic; mm Hg)
In case of renal impairment, proteinuria > 1g/24h |
<130/80
<125/75
|
| Glycaemic control |
|
HbA1C (%)a
|
≤6.5 |
| Glucose expressed as venous plasma mmol/L (mg/dL) |
|
Fasting |
<6.0 (108) |
Post-prandial (peak) |
<7.5 (135) diabetes type 2
7.5-9.0 (135-160) diabetes type 1
|
| Lipid profile expressed in mmol/L (mg/dL) |
|
Total cholesterol |
<4.5 (175) |
LDL-cholesterol |
<1.8 (70) |
HDL-cholesterol |
|
Men |
>1.0 (40) |
Women |
>1.2 (>46) |
Triglyceridesb |
<1.7 (<150) |
TC/HDLb |
<3 |
| Smoking cessation |
Obligatory |
| Regular physical activity (min/day) |
>30-45 |
| Weight control |
|
Body mass index (BMI) (kg/m2)
| <25 |
In case of overweight weight reduction (%)
| 10 |
| Waist (optimum; ethnic specific; cm) |
|
Men
| <94 |
Women |
<80 |
| Dietary habits |
|
Salt intake (g/day) |
<6 |
Fat intake (% of dietary energy) |
|
Saturated |
<10 |
Trans fat |
<2 |
Polyunsaturated n-6 |
4-8 |
Polyunsaturated n-3 |
2 g/day of linolenic acid and 200 mg/day of very long chain fatty acids |
a Diabetes Control and Complication Trial-standardized, for recalculation formula for some national standards in Europe.
b Not recommended for guiding treatment, but recommended for metabolic/risk assessment
|
Specific Treatment
Thrombolysis
Patients with acute myocardial infarction (AMI) and diabetes should be considered for thrombolytic therapy on the same grounds as their non-diabetic counterparts. Class IIa, Level of Evidence A.
Early Revascularization
Whenever possible, patients with diabetes and ACS should be offered early angiography and mechanical revascularization. Class IIa, Level of Evidence B.
Anti-ischaemic Medication
Beta-blockers reduce morbidity and mortality in patients with diabetes and ACS. Class IIa, Level of Evidence B.
Aspirin should be given for the same indications and in similar dosages to diabetic and non-diabetic patients. Class II, Level of Evidence B.
Adenosine diphosphate (ADP) receptor-dependent platelet activation (clopidogrel) should be considered in diabetic patients with ACS in addition to aspirin. Class IIa, Level of Evidence C.
ACE-Inhibitors
The addition of an ACE-inhibitor to other effective therapies reduces the risk for cardiovascular events in patients with diabetes and established cardiovascular disease. Class I, Level of Evidence A.
Metabolic Support and Control
Diabetic patients with AMI benefit from tight glucometabolic control. This may be accomplished by different treatment strategies. Class IIa, Level of Evidence B.
Revascularization (Intervention by Surgery or Percutaneous Coronary Intervention [PCI] Angioplasty)
Treatment decisions regarding revascularization in patients with diabetes should favour coronary artery bypass graft (CABG) surgery over percutaneous intervention. Class IIa, Level of Evidence A.
Whenever possible, patients with diabetes undergoing coronary bypass surgery should be offered at least one and often multiple arterial grafts. Class I, Level of Evidence C.
Adjunctive Therapy
Glycoprotein IIb/IIIa inhibitors are indicated in elective PCI in patients with diabetes. Class I, Level of Evidence B.
When PCI with stent implantation is performed in patients with diabetes, drug-eluting stents (DES) should be used. Class IIa, Level of Evidence B.
Revascularization and Reperfusion in MI
Mechanical reperfusion by means of primary PCI is the revascularization mode of choice in diabetic patients with AMI. Class I, Level of Evidence A.
Heart Failure and Diabetes
Treatment
ACE-inhibitors are recommended as first-line therapy in diabetic patients with reduced left ventricular (LV) dysfunction with or without symptoms of heart failure. Class I, Level of Evidence C.
Angiotensin-II-receptor blockers have similar effects in heart failure as ACE-inhibitors and can be used as an alternative or even as added treatment to ACE-inhibitors. Class I, Level of Evidence C.
Beta-blockers in the form of metoprolol, bisoprolol, and carvedilol are recommended as first-line therapy in diabetic patients with heart failure. Class I, Level of Evidence C.
Diuretics, in particular loop diuretics, are important for symptomatic treatment of patients with fluid overload due to heart failure. Class IIa, Level of Evidence C.
Aldosterone antagonists may be added to ACE-inhibitors, beta-blockers, and diuretics in diabetic patients with severe heart failure. Class IIb, Level of Evidence C.
Arrhythmias: Atrial Fibrillation (AF) and Sudden Death
Diabetes, AF, and Risk of Stroke
Aspirin and anticoagulant use as recommended for patients with AF should be rigorously applied in diabetic patients with AF to prevent stroke. Class I, Level of Evidence C.
Chronic oral anticoagulant therapy in a dose adjusted to achieve a target international normalized ration (INR) of 2 to 3 should be considered in diabetic patients with AF and one other moderate risk factor for thromboembolism, unless contraindicated. Class IIa, Level of Evidence C.
Sudden Cardiac Death
Control of glycaemia even in the pre-diabetic stage is important to prevent the development of the alterations that pre-dispose to sudden cardiac death. Class I, Level of Evidence C.
Microvascular disease and nephropathy are indicators of increased risk of sudden cardiac death in diabetic patients. Class IIa, Level of Evidence B.
Peripheral and Cerebrovascular Disease
Peripheral Vascular Disease
All patients with type 2 diabetes and CVD are recommended treatment with low-dose aspirin. Class IIa, Level of Evidence B.
In diabetic patients with peripheral vascular disease, treatment with clopidogrel or low molecular weight heparin may be considered in certain cases. Class IIb, Level of Evidence B.
Patients with critical limb ischaemia should if possible, undergo revascularization procedures. Class I, Level of Evidence B.
An alternative treatment for patients with critical limb ischaemia not suited for revascularization is prostacyclin infusion. Class IIa, Level of Evidence A.
Stroke
Prevention of Stroke
Normalization of blood pressure is recommended in all patients with diabetes for the prevention of stroke. Class I, Level of Evidence A.
For stroke prevention, blood pressure lowering is more important than the choice of drug. Inhibition of the renin-angiotensin-aldosterone system may have additional benefits beyond blood pressure lowering per se. Class IIa, Level of Evidence B.
Inhibition of the renin-angiotensin-aldosterone system may be considered also in diabetic patients with normal blood pressure levels. Class IIa, Level of Evidence B.
Patients with stroke should be treated with statins according to the same principles as non-diabetic subjects with stroke. Class I, Level of Evidence B.
Antiplatelet therapy with aspirin is recommended for primary and secondary prevention at stroke. Class I, Level of Evidence B.
Treatment of Acute Stroke
Patients with acute stroke and diabetes should be treated according to the same principles as stroke patients without diabetes. Class IIa, Level of Evidence C.
Optimization of metabolic conditions including glycaemic control should be considered as in any other acute disease condition. Class IIa, Level of Evidence C.
Intensive Care
Strict blood glucose control with intensive insulin therapy improves mortality and morbidity of adult cardiac surgery patients. Class I, Level of Evidence B.
Strict blood glucose control with intensive insulin therapy improves mortality and morbidity of adult critically ill patients. Class I, Level of Evidence A.
Health Economics and Diabetes
Lipid-lowering treatment provides a cost-effective way of preventing complications. Class I, Level of Evidence A.
Tight control of hypertension is cost-effective. Class I, Level of Evidence A.
Definitions:
Classes of Recommendations
Class I: Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective
Class II: Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment or procedure
Class IIa: Weight of evidence/opinion is in favour of usefulness/efficacy
Class IIb: Usefulness/efficacy is less well established by evidence/opinion
Class III: Evidence or general agreement that the treatment or procedure is not useful/effective and in some cases may be harmful
Levels of Evidence
Level of Evidence A: Data derived from multiple randomized clinical trials or meta-analyses
Level of Evidence B: Data derived from a single randomized clinical trial or large non-randomized studies
Level of Evidence C: Consensus of opinion of the experts and/or small studies, retrospective studies, registries
