Grant: Travel Awards - Institute Community Support

Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by erratic electrical activity in the upper chambers of the heart (the atria), resulting in irregular contractions and an increased risk for stroke. Diabetes mellitus (DM) is an independent risk factor for AF, which substantially worsens outcomes for diabetic patients. Type 1 DM (T1DM) is defined by the insufficient production of insulin, a hormone that controls how the body uses sugar in the bloodstream. This lack of insulin can stress the heart and affects its behavior. The objective of this study was to determine how insulin alters the electrical properties of the atria and plays a role in the development of AF in the setting of T1DM. We found that T1DM mice were more susceptible to AF and displayed notable alterations in ECG parameters commonly associated with AF. Right atrial conduction velocity, which indicates the speed at which electric signals travel in the heart, was also reduced in mice with T1DM. This is known to be a contributing factor in AF progression. In isolated heart cells, electrical properties were also impaired in a similar manner. Acute insulin treatment (30 min) in mice with T1DM partially reversed these effects while chronic insulin treatment (4 weeks) resulted in even greater improvements. Our studies show that at the cellular level, insulin acts upon sodium channels, which are small proteins that play a critical role in determining electrical conduction in the heart. Chronic insulin treatment also reduced AF susceptibility in T1DM mice. From this study, we were able to conclude that AF in T1DM is associated with slowed atrial conduction and impaired electrical properties at the cellular level, and that insulin can reverse some of these effects. This suggests there is potential for the identification of a therapeutic target that may aid in the prevention of this dangerous arrhythmia in patients with T1DM.