The main novel feature in the diagnosis of DM is the introduction of glycated hemoglobin A1c (HbA1c) as a valid criterion (HbA1c ≥ 6.5%). Currently, the American Diabetes Association (ADA) and the World Health Organization share the same criteria but differ in their strategy. The ADA recommends fasting glucose (FG) and HbA1c determination, while the World Health Organization recommends FG and, if necessary, an oral glucose tolerance test (OGTT); the recommendation of the ADA is much more feasible, although an important caveat is the lack of diagnostic sensitivity of HbA1c, especially in patients with CVD.5 In contrast, the disadvantages of OGTT are that it involves more complex logistics and lack s reproducibility, while its advantage is its higher diagnostic sensitivity. The guidelines remind us that the definition of DM is based on the glucose level at which diabetic retinopathy occurs, which does not mean that lower levels are innocuous. The document stresses that prediabetic states (IFG plus IGT) increase the risk of CVD and that it is important to identify them. However, the recommended strategy consists of lifestyle changes, which have not generally reduced cardiovascular mortality, although such modifications do delay progression to DM. Because there are no differences in the approach to HbA1c in the prediabetes range (5.7%-6.4%) and IGT, the ADA does not advocate the performance of an OGTT. While this might be true for IGT, it is not true for possible new diagnoses of DM based on the results of OGTT, which would allow initiation of metformin therapy and would modify the thresholds of secondary prevention.

In the general population or the population with one or more risk factors and without CVD, the risk of developing DM is calculated through specific tables. If the risk is high, laboratory determinations are performed. When CVD is already established, the guidelines advocate direct determination of FG and HbA1c and the use of OGTT as a complementary test, if necessary. What the guidelines do not provide is a clearly defined strategy for how and when to screen for DM. The 2007 document recommended systematic performance of OGTT in all patients with CVD; however, it has become clear that this recommendation is not feasible and hs not been widely adopted by cardiologists. Although hospital admission would be an opportune moment to perform OGTT, an important consideration is that the results of OGTT could be somewhat falsified by stress hyperglycemia; the guidelines recommend delaying the test for 4 to 5 days after an acute coronary syndrome (ACS), thus supporting the use of OGTT in this scenario. The guidelines reprint a strategy to optimize the indication for OGTT according to a risk model, which may be a practical way to implement the current recommendations. Another possibility is to determine FG and HbA1c before discharge and, depending on the results and other risk factors, to indicate OGTT.5 Equally, this practice could be incorporated in cardiac rehabilitation and secondary prevention programs, independently of the healthcare level in which they are performed.

Greater importance is attached to diet, but the updated guidelines are much more flexible and no longer recommend strict proportions of total energy provided by the major macronutrients, stressing instead appropriate energy intake adapted to the requirements of each patient and a diet based on fruits, vegetables, cereals, low-fat protein sources, and limited intake of saturated and trans-saturated fatty acids. The remaining recommendations are classical: quantifying and distributing carbohydrate intake, limiting salt consumption, and increasing fiber intake; there is no justification for antioxidant supplements (vitamins E and C).

An important novelty is that–in light of the PREDIMED trial,7 which demonstrated that the Mediterranean diet is associated with a lower incidence of major cardiovascular events and in which 50% of the participants were diabetic-, the percentage of dietary fat can be increased with vegetable fats, especially from extra virgin olive oil, dried fruits, and fish oils. Despite the energy contribution of these foods, a substudy of the PREDIMED trial7 also reported a reduction in the incidence of DM and metabolic syndrome.

The recommendations on physical exercise and smoking are traditional: aerobic exercise and resistance training should be carried out within a structured program for at least 150 minutes per week, regularly, and over time. Smokers should be offered a smoking cessation program that should include pharmacological support.

After stressing that CVD is best prevented in diabetic individuals by tight control of all cardiovascular risk factors (CVRF), the guidelines attempt to provide answers to 2 highly important questions:

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  Glycemic targets to prevent cardiovascular complications. The continuous relationship between blood glycemic levels and microvascular complications, with no discernible threshold, despite the clear benefit of an HbA1c level < 7.5%, is less clear for macrovascular complications. Despite the strong association between glycemia and macrovascular complications, the studies that have evaluated the effect of tight glycemic control have reported discrepant results in the prevention of cardiovascular events. Thus, some studies concluded that that lowering HbA1c by 1% in the medium-term reduced the relative risk of fatal infarctions by 15%, with no effect on the risk of stroke or all-cause mortality. The benefit was greater in patients with more recent onset of DM, those with the best glycemic control, and those without CVD. In contrast, some data show that glycemic control in the long term is important to reduce macrovascular complications: prolonged follow-ups are required to demonstrate a benefit and early glycemic control is important to prevent irreversible lesions. It is clear that, to prevent microvascular complications, the target should be HbA1c < 7%. It is more difficult to define the target to prevent macrovascular complications, especially in the presence of established CVD. Glycemic targets should be individually tailored: for patients with a recent diagnosis, young persons and those without comorbidities, HbA1c should be between 6% and 6.5%; for the remainder, HbA1c should be < 7%, although this target may be less stringent (7.5%-8%) in elderly patients and those with multiple comorbidities. In all groups, a priority is to prevent hypoglycemic episodes and any other secondary effects.

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  Choice of glucose-lowering agents. This section discusses very basic concepts, such as the use of a basal-bolus insulin regimen in type 1 DM (T1DM) or metformin as the treatment of choice in T2DM, in the absence of contraindications (glomerular filtration rate < 50 mL/min), without resolving our doubts in clinical practice. The HbA1c obtained with any of these therapeutic options is between 0.5% and 1%, depending mainly on DM duration and the initial HbA1c value. Currently, numerous studies are being conducted to determine the cardiovascular safety profile of the new glucose-lowering agents. The results of SAVOR8 and EXAMINE,9 which evaluated the DPP-4 inhibitors, saxagliptin and alogliptin, respectively, have been presented at a recent ESC congress: although these trials included patients with distinct profiles, there were no differences in mortality or ischemic cardiovascular complications; however, the percentage of admissions for heart failure (HF) was higher in the SAVOR trial.

The specific blood pressure (BP) target for patients with DM has alw a y s ar ouse d contr o v ersy, gi v en that some pr e vious recommendations proposed more stringent control for this group (< 130/80 mmHg) in the absence of conclusive clinical evidence. The current guidelines review the available evidence and recommend BP < 140/85 mmHg, like the 2013 ESC guidelines for arterial hypertension (AHT)10 for diabetic patients.

There are no novelties in pharmacological therapy, except the recommendation not to jointly administer angiotensin-II receptor blockers (ARB-II) and direct renin inhibitors (aliskiren), because this combination has no benefit and has even been shown to increase severe complications. Angiotensin-II receptor blockers and angiotensin-conve rting enzyme inhibitors (ACE-I) are the pharmacological strategy of choice and the guidelines recommend their combination with dihydropyridine calcium channel blockers when more drugs are needed to achieve targets. Neither beta-blockers nor thiazides are mentioned in first-line therapy, due to their potential diabetogenic effect in patients with metabolic syndrome, although there is no evidence of a negative effect in patients with established DM.

Insulin resistance in T2DM leads to lower serum levels of highdensity lipoprotein cholesterol (HDLc) and higher triglyceride levels; even though low-density lipoprotein cholesterol (LDLc) values may not be high, it is the small, dense LDL particles that are particularly atherogenic. The therapeutic targets are LDLc < 70 mg/dL in very high risk DM patients (the majority) and < 100 mg/dL for those at high risk.

Statin use is a major therapeutic strategy, despite the risk of de novo DM with high doses, since this risk is balanced against the reduction in cardiovascular complications and mortality. The addition of ezetimibe is recommended only after enhancing treatment with statins, although there is still no evidence of its benefit on morbidity and mortality. The latest studies on fibrates have demonstrated that they reduce the incidence of cardiovascular complications in diabetic patients (with high triglyceride levels and low HCLc values) but do not reduce cardiovascular mortality. The drugs specifically designed to raise HDLc, torcetrapib and dalcetrapib, have shown no cardiovascular benefit, despite 30% increases in HCLc, and the 2 trials with nicotinic acid have failed. Therefore, to increase HCLc, interventions on lifestyle modification (smoking cessation, a healthy heart diet, weight control and exercise) continue to be essential.

The guidelines review acetylsalicylic acid (AAS), its mechanism of action, and the results of studies on cardiovascular prevention. There is no doubt about its indication in secondary prevention. In contrast, there are no data supporting its use in primary prevention, in which it is only recommended in diabetic patients at high risk (when the 10-year risk of cardiovascular events is > 10%); this recommendation in supported by weak evidence based on expert opinion.

Clopidogrel monotherapy is indicated in patients intolerant to AAS and in those with symptomatic peripheral vascular disease (a recommendation based on a single clinical trial): combined with AAS (low-dose), clopidogrel is indicated in coronary intervention and in ACS for 1 year if the bleeding risk is low. The most novel aspect concerns the new antiplatelet agents (prasugrel and ticagrelor), which are considered superior to clopidogrel in the ACS contexts studied.

The guidelines underline the importance not only of glycemic control in diabetic patients but also of a multifactorial approach, with tight control of all associated risk factors. Targets for BP, exercise, smoking, diet, and weight control generally concur with the ESC guidelines on prevention11 and specific guidelines, while LDLc targets differ from those of guidelines on dyslipidemia,12 which consider all diabetic individuals to be at high risk and that the target should be LDLc < 70 mg/dL.

Although most of the information has been obtained from analyses of subgroups of patients with DM in large trials, the results show similar efficacy in diabetics and nondiabetics. The updated guidelines repeat well-established pharmacological indications and strategies, such as treatment with an ACE-I/ARB-II + statins + antiplatelet agent; the recommendation for beta-blockers carries less weight, but the document justifies and defends their use, despite their “poor metabolic behavior”; there is no doubt about their benefit after a myocardial infarction. Ivabradine is indicated in some situations.

For glycemic control in ACS, 2 strategies are discussed to improve prognosis; metabolic modulation, though glucose-insulin-potassium (GIP), which has not been shown to reduce morbidity and mortality in randomized studies, and glycemic control, although the target is still not well-defined, since some registries indicate a J-or U-shaped relationship between glycemic control and prognosis, implying that both hypoglycemia and hyperglycemia may be prognostically unfavorable. A reasonable conclusion that can be drawn from studies with intensive insulin therapy is that controlling glycemia in patients with acute myocardial infarction will produce a b enef it if hyperglycemia is significant (> 180 mg/dL). Attempts should be made to achieve normal glucose levels but with less stringent targets adapted to distinct comorbidities.

Revascularization procedures continue to be challenged by the higher atherosclerotic burden of coronary artery disease in diabetic patients, with involvement of a greater number of vessels and more diffuse atherosclerosis. There is a higher rate of restenosis after percutaneous coronary interventions (PCI) and saphenous graft occlusion after coronary artery bypass graft surgery.

The updated guidelines repeat most of the recommendations published in 2010 on myocardial revascularization in diabetic patients. Some more recent evidence has been introduced, mainly concerning the longstanding controversy about surgery and PCI, but the literature is considered to be confusing due to bias in the registries, the development of drug-eluting stents and, apart from the FREEDOM trial, 13 the lack of prospective randomized studies. In general, the document concludes that, although PCI is a potential treatment for patients with less complex lesions, surgery is indicated in most diabetic patients with multivessel disease. Data from recent registries also indicate that outcome is better in DM with surgery than with drug-eluting stents. Based on the FREEDOM trial,13 surgery is considered to be superior to PCI in patients with DM and advanced coronary artery disease. Although the guidelines affirm that this trial represents the real world due to its inclusion of a wide variety of patients, this affirmation is questionable, since the trial only included 10% of the patients initially evaluated and its favorable results, especially in surgical mortality, cannot be extrapolated to all centers. It is concluded that the type of intervention should be decided after discussion with the patient, explaining the risks and benefits of the treatment, and after assessment of individual risk and the results of each particular center.

Importantly, signs of disease and physical examination continue to be of great importance in diagnosis and prognosis, with emphasis on the ankle-brachial index. Both primary and secondary prevention underline lifestyle modification, physical exercise, and risk factor control. Initial medical treatment should include antiplatelet agents and statins. Beta-blockers are not contraindicated in diabetic patients with lower extremity artery disease.

Treatment of microvascular disease, both in primary and in secondary prevention, should start with lifestyle modifications and tight glycemic control. The HbA1c target in T1DM and T2DM is < 7%. In BP control, emphasis is placed on renin-angiotensin-aldosterone blockade in the primary and secondary prevention of kidney disease: the recommende d target for patients with retinopathy or nephropathy is < 140/85 mmHg, as in all diabetic patients, except in the presence of proteinuria, in which case the target is lower (systolic BP < 130 mmHg), if tolerated by the patient. Adequate lipid control (plasma cholesterol and triglyceride control) is included in the prevention of kidney disease; no information is provided on retinopathy. Antiplatelet therapy is not contraindicated in patients with retinopathy because there have been no observations of an increase in bleeding. Erythropoietin therapy in patients with diabetic nephropathy involves monitoring the progression of retinopathy and car dio vascular risk . F inall y, the guidelines describ e the ophthalmological treatments required in severe retinopathy.