Letter: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)

Corresponding author: Jae Hyoung Cho https://orcid.org/0000-0003-2235-8874 Department of Endocrinology and Metabolism, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea E-mail: [email protected] Type 2 diabetes mellitus causes many kinds of chronic complications, such as microvascular complications including diabetic retinopathy, nephropathy, neuropathy, and macrovascular complications. Diabetic autonomic neuropathy (DAN) is also one of the most serious complications, and its prevalence varies depending on the cohort to 20% abnormality [1]. DAN may affect many organ systems, especially a wide spectrum of adverse cardiovascular outcomes [2]. Cardiac autonomic neuropathy (CAN) is associated with autonomic cardiomyopathy and is the pre-dispose factor of sudden cardiac death [3]. CAN is considered as a result of damages in the autonomic nerve fibers of heart that innervate the heart and blood vessels, which leads to abnormalities in heart rate control [4]. Therefore, diabetic cardiac autonomic dysfunction is inevitably associated with reduced heart rate variability (HRV) [5]. HRV has been proposed as an indicator of cardiovascular risk because the first manifestation of CAN is a decrement in HRV in a normal heart rate [6]. Glycemic control is considered as an essential treatment for CAN. According to Pop-Busui et al. [7], the early initiation of intensive glucose control in type 1 diabetes mellitus can help minimize the development of CAN. However, the benefit of glycemic control in type 2 diabetes mellitus is not confirmed [1]. Although blood sugar optimization is the most important treatment, it would be difficult to revive already advanced autonomic nervous system complications. Therefore, alternative treatments are needed based on the pathophysiologic aspect of diabetic CAN. One of the possible solutions to treat diabetic CAN originate from that hyperglycemia can increase oxidative stress and cause direct neuronal damage and dysfunction [8]. Therefore, α-lipoic acid (ALA), which is known as a free-radical scavenger and used for treatment of diabetic peripheral polyneuropathy, could be regarded as one of treatment modalities for diabetic CAN by reducing the oxidative stress [9]. Fortunately, in the Deutsche Kardiale Autonome-Neurophathie (DEKAN) study, ALA showed a beneficial effect on HRV index of patients with diabetic CAN [10]. Another study, the Alpha Lipoic Acid in Diabetic Neuropathy (ALADIN) study, showed that ALA could improve neuropathic symptoms such as pain, burning, paresthesia, and numbness [11]. With such background, Lee et al. [12] investigated the effects of high-dose ALA on HRV of type 2 diabetes mellitus patients with CAN in Korea. In this study, the therapeutic effect of high-dose ALA to diabetic CAN presented a positive trend despite the lack of significant results. The standard deviation of normal-to-normal RR intervals, low frequency band and high frequency/low freLetter