Abstract
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.
Highlights
Diabetes affected 422 million adults in 2014 (WHO, 2021), but the incidence and the associated socio-sanitary cost are steadily rising
In 1983, Fein et al described for the first time a lengthening of the cardiac action potential duration (APD) in a rat model of Type 1 diabetes (T1D) (Fein et al, 1983), an effect consistently confirmed in rodent and non-rodent models (Magyar et al, 1992; Casis et al, 2000; Lengyel et al, 2007; Torres-Jacome et al, 2013)
Both T1D and Type 2 diabetes (T2D) induce a cardiac remodeling that leads to mechanical dysfunction and/or cardiac arrhythmias
Summary
Diabetes affected 422 million adults in 2014 (WHO, 2021), but the incidence and the associated socio-sanitary cost are steadily rising. Since TdP occurs in the setting of prolonged QT intervals, QT duration and heart rate-corrected QT duration (QTc) have become qualitative markers of proarrhythmic risk The electrocardiogram of both type 1 and type 2 diabetic patients. This review focuses on the electrical characteristics of the diabetic myocardium, such as reduced conduction velocity and prolonged ventricular repolarization Since these alterations may increase the risk of arrhythmia, evaluating the proarrhythmic risk of new drugs is very relevant for the case of glucose-lowering drugs. We will examine the proarrhythmic safety of antidiabetic drugs and the recommended treatments for type 2 diabetic patients at cardiovascular risk
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