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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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  • 70 Download
  • 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  
  • Effect of Ramipril on Cardiac Autonomic Neuropathy in Patients With Type II Diabetes Mellitus
    Chaitali A Chindhalore, Ganesh N Dakhale, Prathamesh H Kamble, Bharatsing D Rathod, Sunita Kumbhalkar, Mrunal S Phatak
    Cureus.2023;[Epub]     CrossRef
  • Evaluating treatment options for cardiovascular autonomic neuropathy in patients with diabetes mellitus: a systematic review
    Jasmine KaiLi Goh, Leroy Koh
    Diabetology International.2023; 14(3): 224.     CrossRef
  • The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials
    Mahdi Vajdi, Nooshin Noshadi, Shirin Hassanizadeh, Atefeh Bonyadian, Hooria Seyedhosseini-Ghaheh, Gholamreza Askari
    Frontiers in Cardiovascular Medicine.2023;[Epub]     CrossRef
  • Combination Therapy of Alpha-Lipoic Acid, Gliclazide and Ramipril Protects Against Development of Diabetic Cardiomyopathy via Inhibition of TGF-β/Smad Pathway
    George J. Dugbartey, Quinsker L. Wonje, Karl K. Alornyo, Louis Robertson, Ismaila Adams, Vincent Boima, Samuel D. Mensah
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
    Sondre Meling, Davide Bertoli, Dag A. Sangnes, Christina Brock, Asbjørn Drewes, Niels Ejskjaer, Georg Dimcevski, Eirik Søfteland
    Current Diabetes Reviews.2022;[Epub]     CrossRef
  • Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose–response meta-analysis of randomized trials
    Aliyu Tijani Jibril, Ahmad Jayedi, Sakineh Shab-Bidar
    Endocrine Connections.2022;[Epub]     CrossRef
  • Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management
    Scott Williams, Siddig Abdel Raheim, Muhammad Ilyas Khan, Umme Rubab, Prathap Kanagala, Sizheng Steven Zhao, Anne Marshall, Emily Brown, Uazman Alam
    Clinical Therapeutics.2022; 44(10): 1394.     CrossRef
  • An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults
    Mahsa Mahmoudi-Nezhad, Mahdi Vajdi, Mahdieh Abbasalizad Farhangi
    Nutrition.2021; 82: 111041.     CrossRef
  • Management of diabetic neuropathy
    Simona Cernea, Itamar Raz
    Metabolism.2021; 123: 154867.     CrossRef
  • Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy
    Victoria A. Serhiyenko, Ludmila M. Serhiyenko, Volodymyr B. Sehin, Alexandr A. Serhiyenko
    Endocrine Regulations.2021; 55(4): 224.     CrossRef
  • The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials
    Sarah Jeffrey, Punitha Isaac Samraj, Behin Sundara Raj
    Current Diabetes Reviews.2021;[Epub]     CrossRef
  • Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies
    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
    Diabetes & Metabolism Journal.2019; 43(1): 3.     CrossRef
  • Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis
    Mehran Rahimlou, Maryam Asadi, Nasrin Banaei Jahromi, Anahita Mansoori
    Clinical Nutrition ESPEN.2019; 32: 16.     CrossRef
  • Alpha-lipoic acid and diabetic cardiac autonomic neuropathy
    Victoria Serhiyenko, Ludmila Serhiyenko, Alexandr Serhiyenko
    MOJ Public Health.2019; 8(1): 8.     CrossRef
  • 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
The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.
Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim
Korean Diabetes J. 2009;33(6):485-493.   Published online December 1, 2009
  • 2,488 View
  • 20 Download
  • 2 Crossref
AbstractAbstract PDF
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.


Citations to this article as recorded by  
  • The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
    Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
    Journal of Atherosclerosis and Thrombosis.2024;[Epub]     CrossRef
  • Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
    Ki Won Oh
    Korean Diabetes Journal.2009; 33(6): 464.     CrossRef
Leptin is Negatively Associated with Femoral Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes Mellitus.
Jae Han Jeon, Yeun Kyung Choi, Hyun Ae Seo, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, Ju Young Lee, Jung Guk Kim, Bo Wan Kim, In Kyu Lee
Korean Diabetes J. 2009;33(5):421-431.   Published online October 1, 2009
  • 2,233 View
  • 19 Download
  • 1 Crossref
AbstractAbstract PDF
Serum leptin level and bone mineral density (BMD) are widely assumed to be positively associated with body fat mass. Numerous attempts have been made to document the relationship between leptin and BMD, but the results are inconsistent, especially in diabetic patients. METHODS: A total of 60 Korean postmenopausal women with type 2 diabetes mellitus were included in the present study. The BMDs of lumbar spines (L1 to L4) and proximal femurs (trochanter, neck, and total) were measured by dual-energy X-ray absorptiometry (DXA), and biochemical markers including leptin, HbA1c, C-peptide and urine albumin-creatinine ratio (ACR) were measured for each patient. RESULTS: Negative associations between leptin and BMD of femoral neck, trochanter, and total femur in postmenopausal women with type 2 diabetes mellitus were documented in a model adjusted for age, body fat mass, and fasting insulin level (r = -0.308, P = 0.020 and r = - 0.303, P = 0.025 and r = - 0.290, P = 0.032 respectively). Multiple linear regression analysis was performed revealing negative associations between leptin and BMD of the femoral neck (beta = -0.369), trochanter (beta = -0.324), and total femur (beta = -0.317). CONCLUSION: The results of the present study suggest a negative relationship between leptin and femoral BMD. In addition, leptin may have a negative effect on BMD in postmenopausal women with type 2 diabetes mellitus.


Citations to this article as recorded by  
  • Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment
    MK Dutta, R Pakhetra, MK Garg
    Medical Journal Armed Forces India.2012; 68(1): 48.     CrossRef
The Association Between Urinary Albumin to Creatinine Ratio and Coronary Artery Calcification in Type 2 Diabetic Patients.
Ju Young Lee, Yeon Kyung Choi, Hyun Ae Seo, Jae Han Jeon, Jung Eun Lee, Seong Su Moon, Jung Guk Kim, Bo Wan Kim, In Kyu Lee
Korean Diabetes J. 2009;33(4):289-298.   Published online August 1, 2009
  • 2,221 View
  • 20 Download
AbstractAbstract PDF
Atherosclerosis, the most common cause of death in type 2 diabetic patients, is closely associated with coronary artery calcium deposition. The coronary calcifications can be easily measured using coronary calcium scoring computed tomography (CT). And microalbuminuria is known as an independent risk factor of cardiovascular disease. So, we examined the association of urinary albumin to creatinine ratio (UACR) and coronary calcification score (CCS) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who underwent the multidetector CT scanning for the evaluation of CCS at Kyungpook National University Hospital between December 2007 and May 2008, 155 subjects were included. CCS, demographic and laboratory data were assessed. RESULTS: Coronary artery calcifications were identified in 90 patients (51%) and mean, median CCS was 205.8 +/- 476.9, 8.74 (0, 132.0). 60 subjects revealed UACR greater than 30 ug/mg. With the UACR increment, CCS revealed a significant increase (P < 0.001). Age, duration of diabetes, serum Apo A1 level, serum high sensitivity C-reactive protein (hs-CRP) level were also associated with CCS. However, after adjusting for age, UACR and CCS exhibited a significant positive relationship (P = 0.002). CONCLUSION: Increased UACR is associated with coronary artery calcification in type 2 diabetic patients and these results will be useful in early evaluating the presence of macrovascular complications in these patients.
Association of Kir6.2 and Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphisms with Type 2 Diabetes in Koreans.
Jung Eun Lee, Su Won Kim, Hyun Ae Seo, Jae Han Jeon, Seong Su Moon, Hee Kyung Kim, Yun Jeong Doh, Bo Wan Kim, Jung Guk Kim, Min Yoo, In Kyu Lee
Korean Diabetes J. 2007;31(6):455-464.   Published online November 1, 2007
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  • 18 Download
AbstractAbstract PDF
The type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Several variants may contribute significantly to the risk of type 2 diabetes conferring insulin resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory deficiency (Glu23Lys). In this study, we evaluated the association of Pro12Ala variant of the peroxisome proliferator- activated receptor-gamma and the Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11) with the type 2 diabetes in Korean population. METHOD: This study included 331 subjects consisting of 172 patients with type 2 diabetes and 159 non- diabetic control subjects enrolled from the Kyungpook, Keimyung and Catholic university hospital in Daegu, Korea. We genotyped Kir6.2 (Glu23Lys) and PPARgamma (Pro12Ala) polymorphism and examined their association with the type 2 diabetes. RESULT: In the separate analyses, the Kir6.2 Glu23Lys (P = 0.385) and the PPARgamma Pro12Ala (P = 0.191) polymorphism showed no significant association with type 2 diabetes. In addition, the results of our study showed no evidence of a synergistic interaction between Kir6.2 and PPARgamma gene in each group (P = 0.110, P = 0.276). CONCLUSION: In this study, no association was seen between the genetic polymorphisms of Kir6.2, PPARgamma and type 2 diabetes. However, to clarify whether genetic polymorphisms of these genes contribute to the development of type 2 diabetes, further studies involving larger Korean populations may be needed.
Blood Leptin, Anthropometric and Biochemical Parameters in Type 2 Diabetics.
Seong su Moon, Jae han Jeon, Jung eun Lee, Soon hong Park, Hee kyung Kim, Jeong yun Doh, Ye dal Jung, In kyu Lee, Bo wan Kim, Jung guk Kim
Korean Diabetes J. 2007;31(1):75-82.   Published online January 1, 2007
  • 2,209 View
  • 29 Download
  • 1 Crossref
AbstractAbstract PDF
Leptin is a hormone which is produced in adipose tissue and regulates food intake and body weight. Leptin is known to correlate with body adiposity such as body mass index. Blood leptin concentration is not different between non-diabetics and diabetics. And It affect not only food intake but may be one of the key factors in the developement of insulin resistance. Recent studies suggest a complex relationship between leptin and insulin resistance or insulin. Therefore we examined the relationship between leptin and anthropometric, biochemical parameters, and insulin resistance in type 2 diabetics. METHOD: The study subjects were 144 patients with type 2 diabetes who visited Kyungpook national university hospital. Anthropometric parameters such as body fat mass, soft lean mass, BMI, arm circumference, skin fold thickness of several sites were measured. Percent body fat were calculated from Brozek fomula, body density were calculated from Jackson and Pollock fomula. Fasting blood leptin and metabolic varables such as C-peptide, HbA1C, insulin, HDL, LDL, TG, total cholesterol, FFA, HOMA-IR were measured. The relationships of blood leptin concentration with clinical data were analyzed with SPSS program. RESULT: Blood leptin concentrations were 8.2 +/- 5.39 ng/mL in women with type 2 diabetes and 5.1 +/- 5.55 ng/mL in men with type 2 diabetes (P-value: 0.01). Percent body fat, FFA were higher in women than men but arm circumference, soft lean mass, waist circumference were higher in men than women (P-value < 0.05). Leptin concentration correlated with BMI, percent body fat, insulin, TG, body fat mass, waist circumference, HOMA-IR. And insulin, C-peptide, total cholesterol, TG were also correlated with leptin only in women with type 2 diabetes. Waist circumference and percent body fat were independent variables which influence blood leptin concentration in multiple regression analysis. CONCLUSION: Blood leptin concentrations are related to parameters such as percent body fat, waist circumference, BMI, body fat mass, insulin, TG, HOMA-IR in type 2 diabetics. The relationship between leptin and obesity or HOMA-IR suggests that leptin may be a one of factors in developement of insulin resistance.


Citations to this article as recorded by  
  • Prognostic Value of Leptin in Terminally Ill Cancer Patients
    Ji Hyun Hong, So Jin Lee, Sang Mi Kwak, Youn Seon Choi, June Yeong Lee
    The Korean Journal of Hospice and Palliative Care.2012; 15(2): 99.     CrossRef

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