Нейропатия является серьезным осложнением сахарного диабета, лечение которой включает гликемический контроль, патогенетические препараты и симптоматические средства (анальгетики) при необходимости. В данном обзоре приведена оценка эффективности и безопасности a-липоевой кислоты (АЛК) в патогенетической терапии диабетической нейропатии. Механизмы действия АЛК включают снижение окислительного стресса наряду с улучшением эндонейронального кровотока, повышением скорости проводимости по нервным волокнам, а также улучшением ряда других функций нерва. Существует достаточно клинических исследований, соответствующих современным требованиям доказательной медицины, свидетельствующих, что АЛК является эффективным и безопасным препаратом. По обезболивающей эффективности АЛК уступает центральным анальгетикам, но она лучше переносится, имеет более быстрое начало действия, а также дополнительно к аналгезии облегчает парестезии, онемение, снижает/устраняет сенсорный и мышечный дефицит. Поэтому АЛК является препаратом выбора для больных с ранними симптомами нейропатического дефицита, с вегетативной нейропатией сердечно-сосудистой системы и для пациентов с сопутствующей патологией для снижения риска полипрагмазии.
Neuropathy is a serious complication of diabetes mellitus, where treatment involves glycemic control, pathogenic agents and symptomatic agents (analgesics), if necessary. This review shows the efficacy and safety of a-lipoic acid (ALA) in pathogenetic therapy of diabetic neuropathy. Mechanisms of action of ALA include the reduction of oxidative stress while improving endoneuronal blood flow, increase in nerve fibers conduction velocity, as well as the improvement of a number of other nerve functions. There is enough clinical trials, corresponding to modern requirements of evidence-based medicine, evidence that ALA is an effective and safe drug. As analgesic effectiveness of ALA is inferior central analgesics, but it is better tolerated, it has a more rapid onset of action, and in addition to analgesia facilitates paresthesia, numbness, reduces / eliminates muscle and sensory deficits. Therefore, ALA is a drug of choice for patients with early symptoms of neuropathic deficits, with the autonomic neuropathy of the cardiovascular system and for patients with co-morbidities to reduce the risk of polypharmacy.
1. Ametov A, Barinov A, O’Brien P et al. The sensory symptoms of diabetic polyneuropathy are improved with alphalipoic acid. The SYDNEY Trial. Diabetes Care 2003; 26: 770–6.
2. Ametov AS, Novosadova MV, Barinov AN et al. Long-term effect of 3-week intravenous alpha-lipoic acid administration in symptomatic diabetic polyneuropathy with clinical manifestations. Ter Arkh 2010; 82 (12): 61–4.
3. Androne L, Gavan NA, Veresiu IA, Orasan R. In vivo effect of lipoic acid onlipid peroxidation in patients withdiabetic neuropathy. In Vivo 2000; 14: 327–30.
4. Arrezo JC. The use of electrophysiology for the assessment ofdiabetic neuropathy. Neuroscience Research Communications 1997; 21: 13–23. doi: 10.1002/(SICI)1520-6769(199707)21:1!13::AID-NRC203O3.0.CO;2-P
5. Barbiroli B, Medori R, Tritschler HJ, Iotti S. Thioctic acid stimulates muscleATP production in patients withtype-2-diabetes and diabeticpolyneuropathy. Diabetes Stoffwechsel 1996; 5 (Suppl. 3): 71–6.
6. Bartkoski S, Day M. Alpha-Lipoic Acid for Treatment of Diabetic Peripheral Neuropathy. Am Fam Physician 2016; 93 (9): 786.
7. Bierhaus A, Chevion S, Chevion M et al. Advanced glycation end productinduced activation of NF-kB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes 1997; 46: 1481–90.
8. Boulton AJ, Kempler P, Ametov A, Ziegler D. Whither pathogenetictreatments for diabetic polyneuropathy? Diabetes Metab Res Rev 2013; 29: 327–33.
9. Çakici N, Fakkel TM, van Neck JW et al. Systematic review of treatments for diabetic peripheral neuropathy. Diabet Med 2016 Jan 29. doi: 10.1111/dme.13083. [Epub ahead of print]
10. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose controlfor preventing and treating diabeticneuropathy. Cochrane Database Syst Rev 2012; 6: CD007543.
11. Cameron NE, Cotter MA, Horrobin DH, Tritschler HJ. Effectsof a-lipoic acid on neurovascular function in diabetic rats:interaction with essential fatty acids. Diabetologia 1998: 41390–399. doi: 10.1007/s001250050921
12. Cameron NE, Jack AM, Cotter MA. Effect of alpha-lipoic acid on vascularresponses and nociception in diabeticrats. Free Radic Biol Med 2001; 31: 125–35.
13. Coppey LJ, Gellett JS, Davidson EP et al. Effect of antioxidant treatment of streptozotocininduceddiabetic rats on endoneurial blood flow, motor nerveconduction velocity, and vascular reactivity of epineurial arteriolesof the sciatic nerve. Diabetes 2001; 50: 1927–37. doi: 10.2337/diabetes.50.8.1927
14. Coppini DV, Bowtell PA, Weng C et al. Showing neuropathy is related toincreased mortality in diabetic patients – a survival analysis using an acceleratedfailure time model. J Clin Epidemiol 2000; 53: 519–23.
15. Evans JL, Goldfine ID. Alpha-lipoic acid:a multifunctional antioxidant thatimproves insulin sensitivity in patientswith type 2 diabetes. Diabetes Technol Ther 2000; 2: 401–13.
16. Garrett NE, Malcangio M, Dewhurst M, Tomlinson DR. Alpha-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support. Neurosci Lett 1997; 222: 191–4.
17. Haak E, Usadel KH, Kusterer K et al. Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy. Exp Clin Endocrinol Diabetes 2000; 108:1 68–74.
18. Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol 2012; 167: 465–71.
19. Heitzer T, Finckh B, Albers S et al. Beneficial effects of alpha-lipoic acid andascorbic acid on endothelium-dependent,nitric oxide-mediated vasodilation indiabetic patients: relation to parametersof oxidative stress. Free Radic Biol Med 2001; 31: 53–61.
20. Hoffman M, Zimmer G. Lipoate prevention of diabetic microangiopathy. In: Fuchs J, Packer L, Zimmer G, editors. Lipoic acid in health and disease. New York: Marcel Decker, 1997; p. 168–74.
21. Hofmann MA, Schiekofer S, Isermann B et al. Peripheral bloodmononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB. Diabetologia 1999; 42: 222–32.
22. Javed S, Petropoulos IN, Alam U, Malik RA. Treatment of painful diabetic neuropathy. Ther Adv Chronic Dis 20154 6 (1): 15–28. DOI: 10.1177/2040622314552071
23. Kunt T, Forst T, Wilhelm A et al. a-Lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clinical Sci 1999; 96: 75–82. doi: 10.1042/CS19980224
24. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev 2014; 1: CD007115.
25. McIlduff CE, Rutkove SB. Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the treatment of symptomatic diabetic polyneuropathy. Ther Clin Risk Manag 2011; 7: 377–85.
26. Mijnhout GS, Kollen BJ, Alkhalaf A et al. Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int J Endocrinol 2012; 2012: 456279.
27. Mitsui Y, Schmelzer JD, Zollman PJ et al. a-Lipoic acid provides neuroprotection from ischemia–reperfusion injury of peripheral nerve. J Neurol Sci 1999; 163: 11–6. doi: 10.1016/S0022-510X(99)00017-9
28. Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic Acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem 2015; 15 (5): 458–83.
29. Nagamatsu M, Nickander KK, Schmelzer JD et al. Lipoic acid improves nerve blood flow,reduces oxidative stress, and improves distal nerve conduction inexperimental diabetic neuropathy. Diabetes Care 1995; 18: 1160–7. doi:10.2337/diacare.18.8.1160
30. Papanas N, Ziegler D. Efficacy of a-lipoic acid in diabetic neuropathy. Exp Opin Pharmacother 2014; 15 (18): 2721–31.
31. Reljanovic M, Reichel C, Rett K et al. Treatment of diabetic peripheralneuropathy with the antioxidant thiocticacid (alpha-lipoic acid). A two-yearmulticenter randomized double blindplacebo controlled trial (ALADIN II).Free Rad Res 1999; 31: 171–9.
32. Ruessmann H-J. Switching from pathogenetic treatment with α-lipoic acid to gabapentin and other analgesics in painful diabetic neuropathy: a real-world study in outpatients. J Diabetes Complications 2009; 23: 174–7.
33. Ruhnau K-J, Meissner HP, Finn JR et al. Effects of 3-week oral treatmentwith the antioxidant thioctic acid (alphalipoicacid) in symptomatic diabeticpolyneuropathy. Diabet Med 1999; 16: 1040–3.
34. Sola S, Mir MQ, Cheema FA et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the irbesartan and lipoic acid in endothelial dysfunction (ISLAND) study. Circulation 2005; 111: 343–8.
35. Stevens MJ, Obrosova I, Cao X et al. Effects of DL-alpha-lipoic acid onperipheral nerve conduction, blood flow,energy metabolism, and oxidative stressin experimental diabetic neuropathy. Diabetes 2000; 49: 1006–15.
36. Tingting Han, Jiefei Bai, Wei Liu, Yaomin Hu. A systematic review and meta-analysis of a-lipoic acid in the treatment of diabetic peripheral neuropathy Eur J Endocrinol 2012; 167: 465–71.
37. Várkonyi T, Putz Z, Keresztes K et al.Current options and perspectives in the treatment of diabetic neuropathy.Curr Pharm Des 2013; 19: 4981–5007.
38. Vinik AI, Maser RE, Ziegler D. Neuropathy: the crystal ball forcardiovascular disease? Diabetes Care 2010; 33: 1688–90.
39. Wada H, Shintani D, Ohlrogge J. Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production. Proc Natl Acad Sci U.S.A. 1997; 94: 1591–6.
40. Weiskirchen R. Hepatoprotective and Anti-fibrotic Agents: It’s Time to Take the Next Step. Front. Pharmacol 2016; 6: 303. doi: 10.3389/fphar.2015.00303
41. Zhang W-J, Frei B. Alpha-Lipoic acid inhibits TNF-a-induced NF-kB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001; 15: 2423–32.
42. Zhong-Wei Zhang, Xiao-Chao Xu, Ting Liu, Shu Yuan. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases Oxidative. Medicine and Cellular Longevity 2016. Article ID 6859523, 10 pages doi.org/10.1155/2016/6859523
43. Ziegler D, Ametov A, Barinov A et al. Oral treatment with alpha-lipoic acidimproves symptomatic diabeticpolyneuropathy: The SYDNEY 2 trial. Diabetes Care 2006; 29: 2365–70.
44. Ziegler D, Hanefeld M, Ruhnau KJ et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicentre randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care 1999; 22: 1296–301.
45. Ziegler D, Hanefeld M, Ruhnau KJ et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995; 38: 1425–33.
46. Ziegler D, Low PA, Litchy WJ et al. Efficacy and safety of antioxidant treatment with αa-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 2011; 34 (9): 2054–60.
47. Ziegler D, Nowak H, Kempler P et al. Treatment of symptomatic diabeticpolyneuropathy with the antioxidantalpha-lipoic acid: a meta-analysis. Diabet Med 2004; 21: 114–21.
48. Ziegler D, Schatz H, Conrad F et al. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomicneuropathy in NIDDM patients. A 4-month randomized controlledmulticenter trial (DEKAN Study). Diabetes Care 1997; 20: 369–73.
49. Ziegler D, Low PA, Freeman R et al. Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial. J Diabetes Complications 2016; 30 (2): 350–6. doi: 10.1016/j.jdiacomp.2015.10.018. Epub 2015 Nov 10
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________________________________________________
1. Ametov A, Barinov A, O’Brien P et al. The sensory symptoms of diabetic polyneuropathy are improved with alphalipoic acid. The SYDNEY Trial. Diabetes Care 2003; 26: 770–6.
2. Ametov AS, Novosadova MV, Barinov AN et al. Long-term effect of 3-week intravenous alpha-lipoic acid administration in symptomatic diabetic polyneuropathy with clinical manifestations. Ter Arkh 2010; 82 (12): 61–4.
3. Androne L, Gavan NA, Veresiu IA, Orasan R. In vivo effect of lipoic acid onlipid peroxidation in patients withdiabetic neuropathy. In Vivo 2000; 14: 327–30.
4. Arrezo JC. The use of electrophysiology for the assessment ofdiabetic neuropathy. Neuroscience Research Communications 1997; 21: 13–23. doi: 10.1002/(SICI)1520-6769(199707)21:1!13::AID-NRC203O3.0.CO;2-P
5. Barbiroli B, Medori R, Tritschler HJ, Iotti S. Thioctic acid stimulates muscleATP production in patients withtype-2-diabetes and diabeticpolyneuropathy. Diabetes Stoffwechsel 1996; 5 (Suppl. 3): 71–6.
6. Bartkoski S, Day M. Alpha-Lipoic Acid for Treatment of Diabetic Peripheral Neuropathy. Am Fam Physician 2016; 93 (9): 786.
7. Bierhaus A, Chevion S, Chevion M et al. Advanced glycation end productinduced activation of NF-kB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes 1997; 46: 1481–90.
8. Boulton AJ, Kempler P, Ametov A, Ziegler D. Whither pathogenetictreatments for diabetic polyneuropathy? Diabetes Metab Res Rev 2013; 29: 327–33.
9. Çakici N, Fakkel TM, van Neck JW et al. Systematic review of treatments for diabetic peripheral neuropathy. Diabet Med 2016 Jan 29. doi: 10.1111/dme.13083. [Epub ahead of print]
10. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose controlfor preventing and treating diabeticneuropathy. Cochrane Database Syst Rev 2012; 6: CD007543.
11. Cameron NE, Cotter MA, Horrobin DH, Tritschler HJ. Effectsof a-lipoic acid on neurovascular function in diabetic rats:interaction with essential fatty acids. Diabetologia 1998: 41390–399. doi: 10.1007/s001250050921
12. Cameron NE, Jack AM, Cotter MA. Effect of alpha-lipoic acid on vascularresponses and nociception in diabeticrats. Free Radic Biol Med 2001; 31: 125–35.
13. Coppey LJ, Gellett JS, Davidson EP et al. Effect of antioxidant treatment of streptozotocininduceddiabetic rats on endoneurial blood flow, motor nerveconduction velocity, and vascular reactivity of epineurial arteriolesof the sciatic nerve. Diabetes 2001; 50: 1927–37. doi: 10.2337/diabetes.50.8.1927
14. Coppini DV, Bowtell PA, Weng C et al. Showing neuropathy is related toincreased mortality in diabetic patients – a survival analysis using an acceleratedfailure time model. J Clin Epidemiol 2000; 53: 519–23.
15. Evans JL, Goldfine ID. Alpha-lipoic acid:a multifunctional antioxidant thatimproves insulin sensitivity in patientswith type 2 diabetes. Diabetes Technol Ther 2000; 2: 401–13.
16. Garrett NE, Malcangio M, Dewhurst M, Tomlinson DR. Alpha-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support. Neurosci Lett 1997; 222: 191–4.
17. Haak E, Usadel KH, Kusterer K et al. Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy. Exp Clin Endocrinol Diabetes 2000; 108:1 68–74.
18. Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol 2012; 167: 465–71.
19. Heitzer T, Finckh B, Albers S et al. Beneficial effects of alpha-lipoic acid andascorbic acid on endothelium-dependent,nitric oxide-mediated vasodilation indiabetic patients: relation to parametersof oxidative stress. Free Radic Biol Med 2001; 31: 53–61.
20. Hoffman M, Zimmer G. Lipoate prevention of diabetic microangiopathy. In: Fuchs J, Packer L, Zimmer G, editors. Lipoic acid in health and disease. New York: Marcel Decker, 1997; p. 168–74.
21. Hofmann MA, Schiekofer S, Isermann B et al. Peripheral bloodmononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB. Diabetologia 1999; 42: 222–32.
22. Javed S, Petropoulos IN, Alam U, Malik RA. Treatment of painful diabetic neuropathy. Ther Adv Chronic Dis 20154 6 (1): 15–28. DOI: 10.1177/2040622314552071
23. Kunt T, Forst T, Wilhelm A et al. a-Lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clinical Sci 1999; 96: 75–82. doi: 10.1042/CS19980224
24. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev 2014; 1: CD007115.
25. McIlduff CE, Rutkove SB. Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the treatment of symptomatic diabetic polyneuropathy. Ther Clin Risk Manag 2011; 7: 377–85.
26. Mijnhout GS, Kollen BJ, Alkhalaf A et al. Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int J Endocrinol 2012; 2012: 456279.
27. Mitsui Y, Schmelzer JD, Zollman PJ et al. a-Lipoic acid provides neuroprotection from ischemia–reperfusion injury of peripheral nerve. J Neurol Sci 1999; 163: 11–6. doi: 10.1016/S0022-510X(99)00017-9
28. Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic Acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem 2015; 15 (5): 458–83.
29. Nagamatsu M, Nickander KK, Schmelzer JD et al. Lipoic acid improves nerve blood flow,reduces oxidative stress, and improves distal nerve conduction inexperimental diabetic neuropathy. Diabetes Care 1995; 18: 1160–7. doi:10.2337/diacare.18.8.1160
30. Papanas N, Ziegler D. Efficacy of a-lipoic acid in diabetic neuropathy. Exp Opin Pharmacother 2014; 15 (18): 2721–31.
31. Reljanovic M, Reichel C, Rett K et al. Treatment of diabetic peripheralneuropathy with the antioxidant thiocticacid (alpha-lipoic acid). A two-yearmulticenter randomized double blindplacebo controlled trial (ALADIN II).Free Rad Res 1999; 31: 171–9.
32. Ruessmann H-J. Switching from pathogenetic treatment with α-lipoic acid to gabapentin and other analgesics in painful diabetic neuropathy: a real-world study in outpatients. J Diabetes Complications 2009; 23: 174–7.
33. Ruhnau K-J, Meissner HP, Finn JR et al. Effects of 3-week oral treatmentwith the antioxidant thioctic acid (alphalipoicacid) in symptomatic diabeticpolyneuropathy. Diabet Med 1999; 16: 1040–3.
34. Sola S, Mir MQ, Cheema FA et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the irbesartan and lipoic acid in endothelial dysfunction (ISLAND) study. Circulation 2005; 111: 343–8.
35. Stevens MJ, Obrosova I, Cao X et al. Effects of DL-alpha-lipoic acid onperipheral nerve conduction, blood flow,energy metabolism, and oxidative stressin experimental diabetic neuropathy. Diabetes 2000; 49: 1006–15.
36. Tingting Han, Jiefei Bai, Wei Liu, Yaomin Hu. A systematic review and meta-analysis of a-lipoic acid in the treatment of diabetic peripheral neuropathy Eur J Endocrinol 2012; 167: 465–71.
37. Várkonyi T, Putz Z, Keresztes K et al.Current options and perspectives in the treatment of diabetic neuropathy.Curr Pharm Des 2013; 19: 4981–5007.
38. Vinik AI, Maser RE, Ziegler D. Neuropathy: the crystal ball forcardiovascular disease? Diabetes Care 2010; 33: 1688–90.
39. Wada H, Shintani D, Ohlrogge J. Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production. Proc Natl Acad Sci U.S.A. 1997; 94: 1591–6.
40. Weiskirchen R. Hepatoprotective and Anti-fibrotic Agents: It’s Time to Take the Next Step. Front. Pharmacol 2016; 6: 303. doi: 10.3389/fphar.2015.00303
41. Zhang W-J, Frei B. Alpha-Lipoic acid inhibits TNF-a-induced NF-kB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001; 15: 2423–32.
42. Zhong-Wei Zhang, Xiao-Chao Xu, Ting Liu, Shu Yuan. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases Oxidative. Medicine and Cellular Longevity 2016. Article ID 6859523, 10 pages doi.org/10.1155/2016/6859523
43. Ziegler D, Ametov A, Barinov A et al. Oral treatment with alpha-lipoic acidimproves symptomatic diabeticpolyneuropathy: The SYDNEY 2 trial. Diabetes Care 2006; 29: 2365–70.
44. Ziegler D, Hanefeld M, Ruhnau KJ et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicentre randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care 1999; 22: 1296–301.
45. Ziegler D, Hanefeld M, Ruhnau KJ et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995; 38: 1425–33.
46. Ziegler D, Low PA, Litchy WJ et al. Efficacy and safety of antioxidant treatment with αa-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 2011; 34 (9): 2054–60.
47. Ziegler D, Nowak H, Kempler P et al. Treatment of symptomatic diabeticpolyneuropathy with the antioxidantalpha-lipoic acid: a meta-analysis. Diabet Med 2004; 21: 114–21.
48. Ziegler D, Schatz H, Conrad F et al. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomicneuropathy in NIDDM patients. A 4-month randomized controlledmulticenter trial (DEKAN Study). Diabetes Care 1997; 20: 369–73.
49. Ziegler D, Low PA, Freeman R et al. Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial. J Diabetes Complications 2016; 30 (2): 350–6. doi: 10.1016/j.jdiacomp.2015.10.018. Epub 2015 Nov 10
50. Bondar' I.A. Primenenie berlitiona v diabetologii. Effektivnaia farmakoterapiia. Endokrinologiia. 2014; 20: 2–8. [in Russian]
51. Men'shchikova E.B., Lankin V.Z., Zenkov N.K. i dr. Okislitel'nyi stress. Prooksidanty i antioksidanty. M., 2006. [in Russian]
52. Nedosugova L.V. Al'fa-lipoevaia kislota (Espa-lipon) v kompleksnom lechenii diabeticheskoi neiropatii. Mezhdunarodnyi endokrinologicheskii zhurn. 2007; 8 (2): 49–51. [in Russian]
Авторы
Е.Н.Карева
ФГБОУ ВО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2;
ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1 elenakareva@mail.ru
________________________________________________
E.N.Kareva
I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2;
N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1 elenakareva@mail.ru