The present status of our knowledge of the relationship between the heart and diabetes is characterized by two conflicting situations: the first is the increasing awareness that diabetes is a primary risk factor and that cardiovascular disease is the leading cause of death in diabetic patients; the second is that our strategies to counteract this risk have been less effective in diabetic patients than in nondiabetics.

Increased cardiovascular morbidity and mortality
The presence of diabetes mellitus increases mortality for any cause, in particular cardiovascular mortality two- to fourfold. Furthermore, mortality is dramatically increased in the presence of clinical features such as diabetic nephropathy. Although part of this increase can be explained by interaction with other risk factors and by the clustering of diabetes with other risk elements in the so-called ‘metabolic syndrome’, increased cardiovascular mortality and morbidity are conferred by the presence of diabetes per se.
Atherosclerotic plaques tend to develop earlier and be more advanced and more diffuse in diabetic patients. Unfortunately, our reperfusion strategies have proven less efficacious in diabetic patients. In particular, PTCA (with or without stenting) seems to have a catastrophic outcome in these patients, who are affected by a high incidence of reocclusion. Due to silent ischemia, this diagnosis is often achieved later in this patient population.
Furthermore, a complex of different adverse characteristics of diabetes, including endothelial dysfunction and a prothrombotic state, augments the probability of plaque ‘instability’ and occlusion. Diabetes renders patients peculiarly prone to heart failure, resulting from both diffuse coronary heart disease and direct microvascular and myocardial damage. Heart failure is the main cause of death during acute myocardial infarction, the global risk of failure being almost three times higher in the presence of diabetes. 
The above situation is rendered more dramatic by the growing incidence of both type 1 and type 2 diabetes and its incidence is expected to double in the next decade.
Although therapeutic improvements and public health policies for risk factor control have brought about a dramatic reduction in cardiovascular mortality among the general population, this success has not been extended to diabetic patients. In fact, death for any cause including cardiovascular mortality in diabetic patients has only marginally diminished in recent decades.
Theoretically, prevention of cardiovascular complications of diabetes consists of: (1) counteraction of metabolic derangement and (2) reduction of other risk factors known to interact with diabetes. Of course, for each of these aspects it is crucial to know when, how, and to what extent to act. Unfortunately, there is a lack of clinical trials specifically designed to address most of these issues.

Trial outcomes
The impact of therapeutic strategies to reduce cardiovascular events in patients with coronary artery disease and diabetes has been the focus of increasing interest in recent years. The results of trials have sometimes been either difficult to interpret or have failed to shed any light on the issue.
Among trials testing the effects of strict vs. conventional metabolic control, only the DIGAMI (Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction) trial provided clear evidence of positive results in cardiovascular prevention at 1 year.
Conversely, disappointing results of the UKPDS (United Kingdom Prospective Diabetes Study) may have been due to a wide overlap between different subgroups, with potential dilution of differences between beneficial and harmful interventions.
With regard to type 1 diabetes, again an inadequate design compromised the possibility of demonstrating the efficacy of strict metabolic control in reducing long-term mortality in the DCCT (Diabetes Control and Complications Trial), apart from a weak positive trend.
If DIGAMI and possibly the DCCT seem to cautiously suggest the efficacy of insulin in cardiovascular prevention, the effects of other classical pharmacological therapies are much less clear and have been questioned by many experts, while a number of new promising metabolic remedies still lack adequate clinical testing.

In this issue of Heart and Metabolism a variety of basic and clinical aspects of diabetes are discussed. One of the crucial aspects in diabetic patients is the fact that diabetes not only affects the coronary (macro- and micro-) circulation, but also myocyte function. As outlined by Gary Lopaschuk in his article, energy metabolism is altered. In particular, glucose uptake and oxidation decrease, while fatty acid oxidation increases. As a consequence, myocardial contractility decreases.
The risk of developing significant coronary artery disease is also high in diabetic patients because of their increased frequency of dyslipidemia, which is linked to central obesity and insulin resistance. In her review, Michaela Diamant argues that patients with diabetes can be considered ‘postprandial’ throughout the entire day, long-lastingly exposing the arteries to potentially atherogenic triglyceride-enriched particles. Even if patients with type 2 diabetes do not have particularly elevated LDL cholesterol levels, intensive LDL lowering therapy may be effective in reducing ischemic events. 
Fisman and colleagues in their article deal with the important problem of therapeutic strategy in patients with diabetes and coronary artery disease. Apart from the positive effects, these authors discuss the potential negative effects of insulin, of biguanides, and of some sulfonylureas.
In their article Freeman and Langer describe the potential of imaging modalities aimed to assess cardiac sympathetic autonomic dysfunction. Myocardial 123I-labeled metaiodobenzylguanidine uptake is useful in predicting autonomic function in patients with diabetes mellitus.
A recently presented trial, outlined in this issue by Hanna Szwed, demonstrated the therapeutic value of a metabolic agent in patients with stable angina pectoris. There was a significant improvement in all exercise and clinical parameters. Also in the subgroup of patients with diabetes a consistent improvement in exercise parameters was present but, because of the relatively small number of patients, did not reach statistical significance.
Patients with diabetes submitted to PTCA are at risk of restenosis: a case report of a patient with myocardial infarction submitted to thrombolytic therapy and, thereafter, because of recurrent chest pain, treated with PTCA is presented by Jonathan Hill, emphasizing the importance of glycemic control and the metabolic implication of acute ischemia in this type of patient.