Resumen
[EN] Diabetes is a chronic metabolic disease characterized by hyperglycemia in the absence
of treatment. Among the diabetes-associated complications, cardiovascular disease is
the major cause of mortality and morbidity in diabetic patients. Diabetes causes a
complex myocardial dysfunction, referred as diabetic cardiomyopathy, which even in the
absence of other cardiac risk factors results in abnormal diastolic and systolic function.
Besides mechanical abnormalities, altered electrical function is another major feature of
the diabetic myocardium. Both type 1 and type 2 diabetic patients often show cardiac
electrical remodeling, mainly a prolonged ventricular repolarization visible in the
electrocardiogram as a lengthening of the QT interval duration. The underlying
mechanisms at the cellular level involve alterations on the expression and activity of
several cardiac ion channels and their associated regulatory proteins. Consequent
changes in sodium, calcium and potassium currents collectively lead to a delay in
repolarization that can increase the risk of developing life-threatening ventricular
arrhythmias and sudden death. QT duration correlates strongly with the risk of
developing torsade de pointes, a form of ventricular tachycardia that can degenerate
into ventricular fibrillation. Therefore, QT prolongation is a qualitative marker of
proarrhythmic risk, and analysis of ventricular repolarization is therefore required for
the approval of new drugs. To that end, the Thorough QT/QTc analysis evaluates QT
interval prolongation to assess potential proarrhythmic effects. In addition, since diabetic
patients have a higher risk to die from cardiovascular causes than individuals without
diabetes, cardiovascular safety of the new antidiabetic drugs must be carefully evaluated
in type 2 diabetic patients. These cardiovascular outcome trials reveal that some
glucose-lowering drugs actually reduce cardiovascular risk. The mechanism of
cardioprotection might involve a reduction of the risk of developing arrhythmia.