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Diabetes Metab J : Diabetes & Metabolism Journal



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Clinical Diabetes & Therapeutics
Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea
Sol Jae Lee, Su Jin Jeong, Yu Chang Lee, Yong Hoon Lee, Jung Eun Lee, Chong Hwa Kim, Kyung Wan Min, Bong Yun Cha
Diabetes Metab J. 2017;41(4):275-283.   Published online July 6, 2017
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  • 18 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   

Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV).


In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.


Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms2 in the ALA group, whereas it declined by −15.04 ms2 in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events.


Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.


Citations to this article as recorded by  
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    Chaitali A Chindhalore, Ganesh N Dakhale, Prathamesh H Kamble, Bharatsing D Rathod, Sunita Kumbhalkar, Mrunal S Phatak
    Cureus.2023;[Epub]     CrossRef
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    Jasmine KaiLi Goh, Leroy Koh
    Diabetology International.2023; 14(3): 224.     CrossRef
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    George J. Dugbartey, Quinsker L. Wonje, Karl K. Alornyo, Louis Robertson, Ismaila Adams, Vincent Boima, Samuel D. Mensah
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
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    Scott Williams, Siddig Abdel Raheim, Muhammad Ilyas Khan, Umme Rubab, Prathap Kanagala, Sizheng Steven Zhao, Anne Marshall, Emily Brown, Uazman Alam
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    Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M.G. Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F.E. Wenstedt, Agnė Šatrauskienė, Michal Vrablík, Arrigo F.G. Cicero
    Antioxidants.2020; 9(10): 1011.     CrossRef
  • Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet
    Vincenza Spallone
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    Mehran Rahimlou, Maryam Asadi, Nasrin Banaei Jahromi, Anahita Mansoori
    Clinical Nutrition ESPEN.2019; 32: 16.     CrossRef
  • Alpha-lipoic acid and diabetic cardiac autonomic neuropathy
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  • Response: 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)
    Chong Hwa Kim, Sol Jae Lee, Bong Yun Cha
    Diabetes & Metabolism Journal.2017; 41(5): 420.     CrossRef
  • 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 J2017;41:275-83)
    Jeongmin Lee, Jae Hyoung Cho
    Diabetes & Metabolism Journal.2017; 41(5): 417.     CrossRef
Detection of Diabetic Autonomic Neuropathy by 24-Hour Heart Rate Variability Analysis in Type 2 Diabetes Mellitus Patients.
Young Hee Rho, Nan Hee Kim, Dong Lim Kim, Dong Hyun Shin, Sin Gon Kim, Kyung Mook Choi, Woo Hyuk Song, Sei Hyun Baik, Woo Keun Seo, Min Kyu Park, Dong Seop Choi
Korean Diabetes J. 2002;26(3):208-219.   Published online June 1, 2002
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  • 19 Download
AbstractAbstract PDF
Diabetic autonomic neuropathy is a relatively common diabetic complication, associated with high long-term mortality. Ewing's test is known as the 'gold standard' for evaluating and diagnosing this disease, yet is not widely used due to the inconvenient procedures of the test. 24-hour Holter EKG monitoring, and the analytical product, heart rate variability, is being introduced as a relatively simple and reliable procedure for the evaluation of diabetic autonomic neuropathy. We explored whether such heart rate variability products derived from Holter monitoring, correlated with the presence, absence, or severity of diabetes mellitus, and whether it correlated well with conventional autonomic tests. METHODS: We compared 59 type 2 diabetic patients with 71 normal subjects. All underwent 24-hr Holter EKG monitoring and basic autonomic evaluations, such as the head-up tilting, hand grip, and deep breathing-heart rate variability tests. Those who had diabetes also underwent evaluation for basic blood chemistry, and complication studies, for things such as: 24-hour urine albumin excretion, fundoscopy and nerve conduction. RESULTS: Variables for heart rate variability were expressed as SDDN, rMSSD, LF, HF, and LF/HF, where SDDN is the Standard Deviation of all RR intervals, rMSSD the square root of the mean of the sum of the squares of differences between adjacent RR intervals, LF the power in the Low Frequency range and HF the power in the High Frequency range, with LF/HF being the ratio between LF and HF. Heart rate variability was significantly lower in terms of rMSSD, LF, HF, but not in terms of the LF/HF ratio, for the diabetic patients compared to the normal subjects. These three variables also correlated with the conventional autonomic tests of systolic blood pressure changes during standing up (negatively), and heart rate variability during deep breathing (positively). SDDN, rMSSD, LF, and HF also correlated negatively with the duration of diabetes. SDDN, LF and HF were significantly lower among patients who had complications such as: retinopathy, nephropathy or peripheral neuropathy, than in those who did not. CONCLUSION: Heart rate variability was lower in type 2 diabetic patients than the control subjects, which correlated well with the duration of diabetes mellitus, diabetic chronic complications and the conventional autonomic nervous function tests, so could be an useful adjunct or even a replacement, for conventional autonomic nervous system testing procedures. More research is needed in this field.

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