Assessment of Diabetic Cardiac Autonomic Neuropathy in Type I Diabetic Mice

Diabetic cardiac autonomic neuropathy (DCAN) is one of the most common complications of diabetes. One reason why the pathogenesis of DCAN is unclear is that non-invasive assessment of DCAN in humans and animals has been problematic. To overcome this limitation, we utilized a sensitive and non-invasive method to assess cardiac autonomic dysregulation from ECG records. The method, which could be easily applied to humans, is based on principal dynamic mode (PDM) analysis of heart rate variability (HRV). The method is unique, in that is able to separately identify the activities of the parasympathetic and sympathetic systems without pharmacological intervention. In our study, ECG was measured via telemetry in ten sex-and age-matched (4 month old male) C57 (n=5) and Akita (n=5) mice, a model of insulin-dependent type 1 diabetes. The results indicate significant reduced cardiac autonomic function in the diabetic mice in comparison to the controls. Further, both immunohistochemical and Western blot analyses show a reduction in nerve density in Akita mice as compared to the control mice, thus, corroborating our PDM data analysis of HRV records.