Main Article Content
Background. Cardiac autonomic neuropathy is a serious complication of diabetes mellitus that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. Cardiac autonomic neuropathy manifests itself in a spectrum of things, ranging from resting tachycardia and fixed heart rate to the development of silent myocardial infarction. The significance of diabetic cardiac autonomic neuropathy has not been fully appreciated and there is no unified treatment algorithm. The purpose was to investigate the effects of benfotiamine on the heart rate variability, the corrected QT interval, QT dispersion and spatial QRS-T angle in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy. Materials and methods. Thirty-two patients with type 2 diabetes mellitus and definite stage of cardiac autonomic neuropathy were allocated into two treatment groups: control (n = 15) received traditional antihyperglycaemic therapy; group 2 (n = 17) — benfotiamine 300 mg/day for three months in addition to standard treatment. Results. It was found that benfotiamine contributed to an increase in the sum of the squares of differences between adjacent normal-to-normal intervals, pNN50 (Δ% = +45.90 ± 7.91 %, p < 0.05), high-frequency component of heart rate variability during the active (Δ% = +25.80 ± 5.58 %, p < 0.05) and passive periods of the day (Δ% = +21.10 ± 4.17 %, p < 0.05), led to a decrease in the corrected QT interval (Δ% = –7.30 ± 1.36 %, p < 0.01), QT dispersion (Δ% = –27.7 ± 9.0 %, p < 0.01) and spatial QRS-T angle (Δ% = –24.4 ± 10.2 %, p < 0.01). Conclusions. The positive influence of benfotiamine suggests the feasibility of its administration to patients with type 2 diabetes mellitus and definite stage of cardiac autonomic neuropathy.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our edition uses the copyright terms of Creative Commons for open access journals.
Authors, who are published in this journal, agree with the following terms:
- The authors retain rights for authorship of their article and grant to the edition the right of first publication of the article on a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
- Directing the article for the publication to the editorial board (publisher), the author agrees with transmitting of rights for the protection and using the article, including parts of the article, which are protected by the copyrights, such as the author’s photo, pictures, charts, tables, etc., including the reproduction in the media and the Internet; for distributing; for the translation of the manuscript in all languages; for export and import of the publications copies of the writers’ article to spread, bringing to the general information.
- The rights mentioned above authors transfer to the edition (publisher) for the unlimited period of validity and on the territory of all countries of the world.
- The authors guarantee that they have exclusive rights for using of the article, which they have sent to the edition (publisher). The edition (the publisher) is not responsible for the violation of given guarantees by the authors to the third parties.
- The authors have the right to conclude separate supplement agreements that relate to non-exclusive distribution of their article in the form in which it had been published in the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.
- The policy of the journal permits and encourages the publication of the article in the Internet (in institutional repository or on a personal website) by the authors, because it contributes to productive scientific discussion and a positive effect on efficiency and dynamics of the citation of the article.
Spallone V, Ziegler D, Freeman R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27(7):639‐653. doi:10.1002/dmrr.1239.
Spallone V. Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet. Diabetes Metab J. 2019;43(1):3‐30. doi:10.4093/dmj.2018.0259.
Serhiyenko VA, Serhiyenko AA. Diabetic cardiac autonomic neuropathy. In: Saldaña JR, ed. Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues. Basel: Springer, Cham; 2019. 825-850pp. doi: 10.1007/978-3-030-11815-0.
Prince CT, Secrest AM, Mackey RH, Arena VC, Kingsley LA, Orchard TJ. Cardiovascular autonomic neuropathy, HDL cholesterol, and smoking correlate with arterial stiffness markers determined 18 years later in type 1 diabetes. Diabetes Care. 2010;33(3):652‐657. doi:10.2337/dc09-1936.
Voulgari C, Moyssakis I, Perrea D, Kyriaki D, Katsilambros N, Tentolouris N. The association between the spatial QRS-T angle with cardiac autonomic neuropathy in subjects with Type 2 diabetes mellitus. Diabet Med. 2010;27(12):1420‐1429. doi:10.1111/j.1464-5491.2010.03120.x.
Gungor M, Celik M, Yalcinkaya E, et al. The Value of Frontal Planar QRS-T Angle in Patients without Angiographically Apparent Atherosclerosis. Med Princ Pract. 2017;26(2):125‐131. doi:10.1159/000453267.
Walsh JA 3rd, Soliman EZ, Ilkhanoff L, et al. Prognostic value of frontal QRS-T angle in patients without clinical evidence of cardiovascular disease (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol. 2013;112(12):1880‐1884. doi:10.1016/j.amjcard.2013.08.017.
Raposeiras-Roubín S, Virgós-Lamela A, Bouzas-Cruz N, et al. Usefulness of the QRS-T angle to improve long-term risk stratification of patients with acute myocardial infarction and depressed left ventricular ejection fraction. Am J Cardiol. 2014;113(8):1312‐1319. doi:10.1016/j.amjcard.2014.01.406.
Serhiyenko VA, Serhiyenko AA. Omega-3 polyunsaturated fatty acids in the treatment of diabetic cardiovascular autonomic neuropathy: A review. In: Moore SJ, ed. Omega-3: Dietary sources, biochemistry and impact on human health. New York: Nova Science Publishers; 2017. pp. 79-154.
Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):1043‐1065.
Borleffs CJ, Scherptong RW, Man SC, et al. Predicting ventricular arrhythmias in patients with ischemic heart disease: clinical application of the ECG-derived QRS-T angle. Circ Arrhythm Electrophysiol. 2009;2(5):548‐554. doi:10.1161/CIRCEP.109.859108.
Berrone E, Beltramo E, Solimine C, Ape AU, Porta M. Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose. J Biol Chem. 2006;281(14):9307‐9313. doi:10.1074/jbc.M600418200.
Rašić-Milutinović Z, Gluvić Z, Peruničić-Peković Z, Miličević D, Lačković M, Penčić B. Improvement of heart rate variability with benfothiamine and alpha-lipoic acid in type 2 diabetic patients – Pilot study. J Cardiol Ther. 2014;2(1):49-55. doi: 10.12970/2311-052X.2014.02.01.9.
Oh SH, Witek RP, Bae SH, et al. Detection of transketolase in bone marrow-derived insulin-producing cells: benfotiamine enhances insulin synthesis and glucose metabolism. Stem Cells Dev. 2009;18(1):37‐46. doi:10.1089/scd.2007.0255.
Stirban A, Pop A, Tschoepe D. A randomized, double-blind, crossover, placebo-controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes. Diabet Med. 2013;30(10):1204‐1208. doi:10.1111/dme.12240.
Pácal L, Kuricová K, Kaňková K. Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?. World J Diabetes. 2014;5(3):288‐295. doi:10.4239/wjd.v5.i3.288.
González-Ortiz M, Martínez-Abundis E, Robles-Cervantes JA, Ramírez-Ramírez V, Ramos-Zavala MG. Effect of thiamine administration on metabolic profile, cytokines and inflammatory markers in drug-naïve patients with type 2 diabetes. Eur J Nutr. 2011;50(2):145‐149. doi:10.1007/s00394-010-0123-x.
Katare R, Caporali A, Emanueli C, Madeddu P. Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response. J Mol Cell Cardiol. 2010;49(4):625‐638. doi:10.1016/j.yjmcc.2010.05.014.
Boghdadi MA, Afify HE, Sabri N, Makbout K, Elmazar M. Comparative study of vitamin B complex combined with alpha lipoic acid versus vitamin B complex in the treatment of diabetic polyneuropathy in type 2 diabetic patients. J Clin Exp Pharmacol. 2017;7(4):241.
Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008;116(10):600‐605. doi:10.1055/s-2008-1065351.
Pácal L, Tomandl J, Svojanovsky J, et al. Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy. Nephrol Dial Transplant. 2011;26(4):1229‐1236. doi:10.1093/ndt/gfq550.
Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC. The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group. Diabetologia. 1999;42(1):68‐75. doi:10.1007/s001250051115.
Valensi PE, Johnson NB, Maison-Blanche P, Extramania F, Motte G, Coumel P. Influence of cardiac autonomic neuropathy on heart rate dependence of ventricular repolarization in diabetic patients. Diabetes Care. 2002;25(5):918‐923. doi:10.2337/diacare.25.5.918.
Kardys I, Kors JA, van der Meer IM, Hofman A, van der Kuip DA, Witteman JC. Spatial QRS-T angle predicts cardiac death in a general population. Eur Heart J. 2003;24(14):1357‐1364. doi:10.1016/s0195-668x(03)00203-3.
Shoeb M, Ramana KV. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. Free Radic Biol Med. 2012;52(1):182‐190. doi:10.1016/j.freeradbiomed.2011.10.444.
Koufopoulos G, Pafili K, Papanas N. Correlation between type 2 diabetes mellitus and ankle-brachial index in a geographically specific Greek population without peripheral arterial disease. Mìžnarodnij endokrinologìčnij žurnal. 2019;15(7):517-522. doi: 10.22141/2224-0722.214.171.1249.186053.
Ziegler D, Schleicher E, Strom A, et al. Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes. Diabetes Metab Res Rev. 2017;33(4):10.1002/dmrr.2811. doi:10.1002/dmrr.2811.