<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">diaendo</journal-id><journal-title-group><journal-title xml:lang="ru">Сахарный диабет</journal-title><trans-title-group xml:lang="en"><trans-title>Diabetes mellitus</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2072-0351</issn><issn pub-type="epub">2072-0378</issn><publisher><publisher-name>Endocrinology research centre</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14341/DM9597</article-id><article-id custom-type="elpub" pub-id-type="custom">diaendo-9597</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Обзоры</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Нарушение распознавания гипогликемии при сахарном диабете: эпидемиология, механизмы развития, терапевтические подходы</article-title><trans-title-group xml:lang="en"><trans-title>Impaired hypoglycemia awareness in diabetes: epidemiology, mechanisms and therapeutic approaches</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5407-8722</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Климонтов</surname><given-names>Вадим Валерьевич</given-names></name><name name-style="western" xml:lang="en"><surname>Klimontov</surname><given-names>Vadim V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор</p></bio><bio xml:lang="en"><p>MD, PhD, Professor</p></bio><email xlink:type="simple">klimontov@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>&lt;p&gt;Научно-исследовательский институт клинической и экспериментальной лимфологии &amp;ndash; филиал &amp;laquo;Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук&amp;raquo;&lt;/p&gt;</institution><country>Россия</country></aff><aff xml:lang="en"><institution>&lt;p&gt;Research Institute of Clinical and Experimental Lymphology &amp;ndash; Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences&lt;/p&gt;</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>18</day><month>02</month><year>2019</year></pub-date><volume>21</volume><issue>6</issue><fpage>513</fpage><lpage>523</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Климонтов В.В., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Климонтов В.В.</copyright-holder><copyright-holder xml:lang="en">Klimontov V.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.dia-endojournals.ru/jour/article/view/9597">https://www.dia-endojournals.ru/jour/article/view/9597</self-uri><abstract><p>Научно-исследовательский институт клинической и экспериментальной лимфологии – филиал «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск</p><p>Нарушенное распознавание гипогликемии (НРГ) – частое осложнение инсулинотерапии. Периодические проблемы с распознаванием гипогликемии испытывают до половины больных сахарным диабетом (СД) 1 и 2 типа, получающих инсулин, а 15–25% больных имеют постоянное нарушение распознавания.</p><p>Краеугольным камнем в развитии НРГ является рекуррентная гипогликемия. Повторные эпизоды гипогликемии нарушают нейрогуморальный ответ на гипогликемию, уменьшают ее симптоматику и индуцируют неадекватную адаптацию головного мозга к низкому содержанию глюкозы. В связи с этим НРГ можно рассматривать как одно из проявлений феномена «метаболической памяти» при СД.</p><p>Наличие НРГ ассоциировано с повышенным риском тяжелой гипогликемии, страхом гипогликемии и когнитивной дисфункцией. Комбинация этих симптомов составляет синдром НРГ. Развитие НРГ становится серьезным барьером в управлении СД.</p><p>Растущий объем данных свидетельствует об обратимости НРГ. Основой тактики ведения больных с НРГ является профилактика новых эпизодов гипогликемии. Структурированное обучение по специальным программам с психологической поддержкой является наиболее доказанным терапевтическим подходом к коррекции НРГ. Технологические подходы: постоянная подкожная инфузия инсулина, непрерывный мониторинг гликемии в режиме реального времени, системы для введения инсулина с замкнутым контуром («искусственная поджелудочная железа»), трансплантация панкреатических островков показали эффективность в коррекции НРГ в ряде клинических исследований.</p><p>Ведение пациентов с СД и синдромом НРГ требует значительных временных и финансовых затрат. Для коррекции НРГ может быть рекомендован пошаговый подход, предусматривающий персонификацию инсулинотерапии, терапевтическое обучение и высокие медицинские технологии.</p></abstract><trans-abstract xml:lang="en"><p>Impaired awareness of hypoglycemia (IAH) is a frequent complication of insulin therapy. Up to half insulin-treated individuals with type 1 and type 2 diabetes report the problems with hypoglycemia awareness, and 15–25% of patients have a permanent IAH.</p><p>A recurrent hypoglycemia is a cornerstone in IAH formation. The repeated episodes of hypoglycemia impair neurohumoral response to hypoglycemia, reduce its symptoms and induce inadequate brain adaptation to low glucose levels. In this regard, the IAH phenomenon can be considered as an example of "metabolic memory" in diabetes.</p><p>The IAH is associated with episodes of severe hypoglycemia, fear of hypoglycemia and cognitive dysfunction. These associates can be combined into IAH syndrome. Development of IAH becomes a serious barrier in diabetes management.</p><p>A growing body of evidence indicates that IAH is a reversible condition. If the syndrome is present, the hypoglycemia avoidance should be primary goal of the treatment. Structured training under specialized programs with psychological support is the most reasonable therapeutic approach to IAH amending. Technological approaches, including continuous subcutaneous insulin infusion, real-time continuous glucose monitoring, closed-loop insulin delivery systems ("artificial pancreas"), and islet transplantation also showed efficacy in hypoglycemia awareness improvement in some clinical studies.</p><p>The diabetes management in patients with IAH is time-consuming and expensive. Therefore, step-by-step approach, from insulin personalization and therapeutic training to advanced medical technologies, should be recommended for these patients.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>сахарный диабет</kwd><kwd>гипогликемия</kwd><kwd>инсулин</kwd><kwd>головной мозг</kwd><kwd>глюкоза</kwd></kwd-group><kwd-group xml:lang="en"><kwd>diabetes</kwd><kwd>hypoglycemia</kwd><kwd>insulin</kwd><kwd>brain</kwd><kwd>glucose</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Martin-Timon I, Del Canizo-Gomez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes. 2015;6(7):912-926. doi: 10.4239/wjd.v6.i7.912</mixed-citation><mixed-citation xml:lang="en">Martin-Timon I, Del Canizo-Gomez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes. 2015;6(7):912-926. doi: 10.4239/wjd.v6.i7.912</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Frier BM. Impaired Awareness of Hypoglycemia. In: Frier BM, Heller SR, McCrimmon RJ, editors. Hypoglycemia. 3rd ed. Hoboken: John Wiley &amp; Sons; 2014. p. 114-144.</mixed-citation><mixed-citation xml:lang="en">Frier BM. Impaired Awareness of Hypoglycemia. In: Frier BM, Heller SR, McCrimmon RJ, editors. Hypoglycemia. 3rd ed. Hoboken: John Wiley &amp; Sons; 2014. p. 114-144.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Veneman T, Mitrakou A, Mokan M, et al. Induction of Hypoglycemia Unawareness by Asymptomatic Nocturnal Hypoglycemia. Diabetes. 1993;42(9):1233-1237. doi: 10.2337/diab.42.9.1233</mixed-citation><mixed-citation xml:lang="en">Veneman T, Mitrakou A, Mokan M, et al. Induction of Hypoglycemia Unawareness by Asymptomatic Nocturnal Hypoglycemia. Diabetes. 1993;42(9):1233-1237. doi: 10.2337/diab.42.9.1233</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Rooijackers HM, Wiegers EC, van der Graaf M, et al. A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes. Diabetes. 2017;66(7):1990-1998. doi: 10.2337/db16-1535</mixed-citation><mixed-citation xml:lang="en">Rooijackers HM, Wiegers EC, van der Graaf M, et al. A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes. Diabetes. 2017;66(7):1990-1998. doi: 10.2337/db16-1535</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Hendrieckx C, Hagger V, Jenkins A, et al. Severe hypoglycemia, impaired awareness of hypoglycemia, and self-monitoring in adults with type 1 diabetes: Results from Diabetes MILES-Australia. J Diabetes Complications. 2017;31(3):577-582. doi: 10.1016/j.jdiacomp.2016.11.013</mixed-citation><mixed-citation xml:lang="en">Hendrieckx C, Hagger V, Jenkins A, et al. Severe hypoglycemia, impaired awareness of hypoglycemia, and self-monitoring in adults with type 1 diabetes: Results from Diabetes MILES-Australia. J Diabetes Complications. 2017;31(3):577-582. doi: 10.1016/j.jdiacomp.2016.11.013</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Gold AE, Macleod KM, Frier BM. Frequency of Severe Hypoglycemia in Patients With Type I Diabetes With Impaired Awareness of Hypoglycemia. Diabetes Care. 1994;17(7):697-703. doi: 10.2337/diacare.17.7.697</mixed-citation><mixed-citation xml:lang="en">Gold AE, Macleod KM, Frier BM. Frequency of Severe Hypoglycemia in Patients With Type I Diabetes With Impaired Awareness of Hypoglycemia. Diabetes Care. 1994;17(7):697-703. doi: 10.2337/diacare.17.7.697</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Clarke WL, Cox DJ, Gonder-Frederick LA, et al. Reduced Awareness of Hypoglycemia in Adults With IDDM: A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care. 1995;18(4):517-522. doi: 10.2337/diacare.18.4.517</mixed-citation><mixed-citation xml:lang="en">Clarke WL, Cox DJ, Gonder-Frederick LA, et al. Reduced Awareness of Hypoglycemia in Adults With IDDM: A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care. 1995;18(4):517-522. doi: 10.2337/diacare.18.4.517</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Pedersen-Bjergaard U, Agerholm-Larsen B, Pramming S, et al. Activity of angiotensin-converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus. Lancet. 2001;357(9264):1248-1253. doi: 10.1016/s0140-6736(00)04405-6</mixed-citation><mixed-citation xml:lang="en">Pedersen-Bjergaard U, Agerholm-Larsen B, Pramming S, et al. Activity of angiotensin-converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus. Lancet. 2001;357(9264):1248-1253. doi: 10.1016/s0140-6736(00)04405-6</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Geddes J, Wright RJ, Zammitt NN, et al. An Evaluation of Methods of Assessing Impaired Awareness of Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2007;30(7):1868-1870. doi: 10.2337/dc06-2556</mixed-citation><mixed-citation xml:lang="en">Geddes J, Wright RJ, Zammitt NN, et al. An Evaluation of Methods of Assessing Impaired Awareness of Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2007;30(7):1868-1870. doi: 10.2337/dc06-2556</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Zhu L, Ang LC, Tan WB, et al. A study to evaluate the prevalence of impaired awareness of hypoglycaemia in adults with type 2 diabetes in outpatient clinic in a tertiary care centre in Singapore. Ther Adv Endocrinol Metab. 2017;8(5):69-74. doi: 10.1177/2042018817707422</mixed-citation><mixed-citation xml:lang="en">Zhu L, Ang LC, Tan WB, et al. A study to evaluate the prevalence of impaired awareness of hypoglycaemia in adults with type 2 diabetes in outpatient clinic in a tertiary care centre in Singapore. Ther Adv Endocrinol Metab. 2017;8(5):69-74. doi: 10.1177/2042018817707422</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Hatle H, Bjorgaas MR, Ro TB, et al. Fear of hypoglycaemia and its relation to hypoglycaemia awareness and symptom intensity in Type 1 diabetes. Diabetes Res Clin Pract. 2018;137:213-220. doi: 10.1016/j.diabres.2018.01.014</mixed-citation><mixed-citation xml:lang="en">Hatle H, Bjorgaas MR, Ro TB, et al. Fear of hypoglycaemia and its relation to hypoglycaemia awareness and symptom intensity in Type 1 diabetes. Diabetes Res Clin Pract. 2018;137:213-220. doi: 10.1016/j.diabres.2018.01.014</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Conget I, Avila D, Gimenez M, et al. Impaired awareness of hypoglycaemia in subjects with type 1 diabetes. Results of an online survey in a diabetes web site. Endocrinol Nutr. 2016;63(3):121-125. doi: 10.1016/j.endonu.2015.11.003</mixed-citation><mixed-citation xml:lang="en">Conget I, Avila D, Gimenez M, et al. Impaired awareness of hypoglycaemia in subjects with type 1 diabetes. Results of an online survey in a diabetes web site. Endocrinol Nutr. 2016;63(3):121-125. doi: 10.1016/j.endonu.2015.11.003</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Abraham MB, Gallego PH, Brownlee WM, et al. Reduced prevalence of impaired awareness of hypoglycemia in a population-based clinic sample of youth with type 1 diabetes. Pediatr Diabetes. 2017;18(8):729-733. doi: 10.1111/pedi.12460</mixed-citation><mixed-citation xml:lang="en">Abraham MB, Gallego PH, Brownlee WM, et al. Reduced prevalence of impaired awareness of hypoglycemia in a population-based clinic sample of youth with type 1 diabetes. Pediatr Diabetes. 2017;18(8):729-733. doi: 10.1111/pedi.12460</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Graveling AJ, Noyes KJ, Allerhand MH, et al. Prevalence of impaired awareness of hypoglycemia and identification of predictive symptoms in children and adolescents with type 1 diabetes. Pediatr Diabetes. 2014;15(3):206-213. doi: 10.1111/pedi.12077</mixed-citation><mixed-citation xml:lang="en">Graveling AJ, Noyes KJ, Allerhand MH, et al. Prevalence of impaired awareness of hypoglycemia and identification of predictive symptoms in children and adolescents with type 1 diabetes. Pediatr Diabetes. 2014;15(3):206-213. doi: 10.1111/pedi.12077</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Pedersen-Bjergaard U, Aronson R, Gydesen H, et al. Hypoglycaemia awareness and risk of severe hypoglycaemia in the Global HAT study of type 1 and type 2 diabetes. In: Proceedings of the IDF Congress; Abu Dhabi, 4-8 Dec 2017.</mixed-citation><mixed-citation xml:lang="en">Pedersen-Bjergaard U, Aronson R, Gydesen H, et al. Hypoglycaemia awareness and risk of severe hypoglycaemia in the Global HAT study of type 1 and type 2 diabetes. In: Proceedings of the IDF Congress; Abu Dhabi, 4-8 Dec 2017.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Olsen SE, Asvold BO, Frier BM, et al. Hypoglycaemia symptoms and impaired awareness of hypoglycaemia in adults with Type 1 diabetes: the association with diabetes duration. Diabet Med. 2014;31(10):1210-1217. doi: 10.1111/dme.12496</mixed-citation><mixed-citation xml:lang="en">Olsen SE, Asvold BO, Frier BM, et al. Hypoglycaemia symptoms and impaired awareness of hypoglycaemia in adults with Type 1 diabetes: the association with diabetes duration. Diabet Med. 2014;31(10):1210-1217. doi: 10.1111/dme.12496</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Schouwenberg BJ, Coenen MJ, Paterson AD, et al. Genetic determinants of impaired awareness of hypoglycemia in type 1 diabetes. Pharmacogenet Genomics. 2017;27(9):323-328. doi: 10.1097/FPC.0000000000000295</mixed-citation><mixed-citation xml:lang="en">Schouwenberg BJ, Coenen MJ, Paterson AD, et al. Genetic determinants of impaired awareness of hypoglycemia in type 1 diabetes. Pharmacogenet Genomics. 2017;27(9):323-328. doi: 10.1097/FPC.0000000000000295</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Fanelli CG, Epifano L, Rambotti AM, et al. Meticulous Prevention of Hypoglycemia Normalizes the Glycemic Thresholds and Magnitude of Most of Neuroendocrine Responses to, Symptoms of, and Cognitive Function During Hypoglycemia in Intensively Treated Patients With Short-Term IDDM. Diabetes. 1993;42(11):1683-1689. doi: 10.2337/diab.42.11.1683</mixed-citation><mixed-citation xml:lang="en">Fanelli CG, Epifano L, Rambotti AM, et al. Meticulous Prevention of Hypoglycemia Normalizes the Glycemic Thresholds and Magnitude of Most of Neuroendocrine Responses to, Symptoms of, and Cognitive Function During Hypoglycemia in Intensively Treated Patients With Short-Term IDDM. Diabetes. 1993;42(11):1683-1689. doi: 10.2337/diab.42.11.1683</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Cranston I, Lomas J, Amiel SA, et al. Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes. Lancet. 1994;344(8918):283-287. doi: 10.1016/s0140-6736(94)91336-6</mixed-citation><mixed-citation xml:lang="en">Cranston I, Lomas J, Amiel SA, et al. Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes. Lancet. 1994;344(8918):283-287. doi: 10.1016/s0140-6736(94)91336-6</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Olsen SE, Bjorgaas MR, Asvold BO, et al. Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes Is Not Associated With Autonomic Dysfunction or Peripheral Neuropathy. Diabetes Care. 2016;39(3):426-433. doi: 10.2337/dc15-1469</mixed-citation><mixed-citation xml:lang="en">Olsen SE, Bjorgaas MR, Asvold BO, et al. Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes Is Not Associated With Autonomic Dysfunction or Peripheral Neuropathy. Diabetes Care. 2016;39(3):426-433. doi: 10.2337/dc15-1469</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Mitrakou A, Fanelli C, Veneman T, et al. Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med. 1993;329(12):834-839. doi: 10.1056/NEJM199309163291203</mixed-citation><mixed-citation xml:lang="en">Mitrakou A, Fanelli C, Veneman T, et al. Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med. 1993;329(12):834-839. doi: 10.1056/NEJM199309163291203</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Yong TY, Phillips L, Horowitz M, Giles N. Severe hypoglycaemic unawareness in a patient with insulinoma. Intern Med J. 2007;37(2):141-142. doi: 10.1111/j.1445-5994.2007.01255.x</mixed-citation><mixed-citation xml:lang="en">Yong TY, Phillips L, Horowitz M, Giles N. Severe hypoglycaemic unawareness in a patient with insulinoma. Intern Med J. 2007;37(2):141-142. doi: 10.1111/j.1445-5994.2007.01255.x</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Klimontov VV, Myakina NE. Glucose variability indices predict the episodes of nocturnal hypoglycemia in elderly type 2 diabetic patients treated with insulin. Diabetes Metab Syndr. 2017;11(2):119-124. doi: 10.1016/j.dsx.2016.08.023</mixed-citation><mixed-citation xml:lang="en">Klimontov VV, Myakina NE. Glucose variability indices predict the episodes of nocturnal hypoglycemia in elderly type 2 diabetic patients treated with insulin. Diabetes Metab Syndr. 2017;11(2):119-124. doi: 10.1016/j.dsx.2016.08.023</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Pacaud D, Hermann JM, Karges B, et al. Risk of recurrent severe hypoglycemia remains associated with a past history of severe hypoglycemia up to 4 years: Results from a large prospective contemporary pediatric cohort of the DPV initiative. Pediatr Diabetes. 2018;19(3):493-500. doi: 10.1111/pedi.12610</mixed-citation><mixed-citation xml:lang="en">Pacaud D, Hermann JM, Karges B, et al. Risk of recurrent severe hypoglycemia remains associated with a past history of severe hypoglycemia up to 4 years: Results from a large prospective contemporary pediatric cohort of the DPV initiative. Pediatr Diabetes. 2018;19(3):493-500. doi: 10.1111/pedi.12610</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Orban BO, Routh VH, Levin BE, Berlin JR. Direct effects of recurrent hypoglycaemia on adrenal catecholamine release. Diab Vasc Dis Res. 2015;12(1):2-12. doi: 10.1177/1479164114549755</mixed-citation><mixed-citation xml:lang="en">Orban BO, Routh VH, Levin BE, Berlin JR. Direct effects of recurrent hypoglycaemia on adrenal catecholamine release. Diab Vasc Dis Res. 2015;12(1):2-12. doi: 10.1177/1479164114549755</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">George E, Harris N, Bedford C, et al. Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects. Diabetologia. 1995;38(10):1183-1190. doi: 10.1007/bf00422367</mixed-citation><mixed-citation xml:lang="en">George E, Harris N, Bedford C, et al. Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects. Diabetologia. 1995;38(10):1183-1190. doi: 10.1007/bf00422367</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Moheet A, Kumar A, Eberly LE, et al. Hypoglycemia-associated autonomic failure in healthy humans: comparison of two vs three periods of hypoglycemia on hypoglycemia-induced counterregulatory and symptom response 5 days later. J Clin Endocrinol Metab. 2014;99(2):664-670. doi: 10.1210/jc.2013-3493</mixed-citation><mixed-citation xml:lang="en">Moheet A, Kumar A, Eberly LE, et al. Hypoglycemia-associated autonomic failure in healthy humans: comparison of two vs three periods of hypoglycemia on hypoglycemia-induced counterregulatory and symptom response 5 days later. J Clin Endocrinol Metab. 2014;99(2):664-670. doi: 10.1210/jc.2013-3493</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Adler GK, Bonyhay I, Failing H, et al. Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control. Diabetes. 2009;58(2):360-366. doi: 10.2337/db08-1153</mixed-citation><mixed-citation xml:lang="en">Adler GK, Bonyhay I, Failing H, et al. Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control. Diabetes. 2009;58(2):360-366. doi: 10.2337/db08-1153</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Cryer PE. Mechanisms of Hypoglycemia-Associated Autonomic Failure and Its Component Syndromes in Diabetes. Diabetes. 2005;54(12):3592-3601. doi: 10.2337/diabetes.54.12.3592</mixed-citation><mixed-citation xml:lang="en">Cryer PE. Mechanisms of Hypoglycemia-Associated Autonomic Failure and Its Component Syndromes in Diabetes. Diabetes. 2005;54(12):3592-3601. doi: 10.2337/diabetes.54.12.3592</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Dagogo-Jack S. Philip E. Cryer, MD: Seminal Contributions to the Understanding of Hypoglycemia and Glucose Counterregulation and the Discovery of HAAF (Cryer Syndrome). Diabetes Care. 2015;38(12):2193-2199. doi: 10.2337/dc15-0533</mixed-citation><mixed-citation xml:lang="en">Dagogo-Jack S. Philip E. Cryer, MD: Seminal Contributions to the Understanding of Hypoglycemia and Glucose Counterregulation and the Discovery of HAAF (Cryer Syndrome). Diabetes Care. 2015;38(12):2193-2199. doi: 10.2337/dc15-0533</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Klimontov VV, Myakina NE, Tyan NV. Heart rate variability is associated with interstitial glucose fluctuations in type 2 diabetic women treated with insulin. Springerplus. 2016;5:337. doi: 10.1186/s40064-016-1932-z</mixed-citation><mixed-citation xml:lang="en">Klimontov VV, Myakina NE, Tyan NV. Heart rate variability is associated with interstitial glucose fluctuations in type 2 diabetic women treated with insulin. Springerplus. 2016;5:337. doi: 10.1186/s40064-016-1932-z</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Bednarik P, Moheet AA, Grohn H, et al. Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes. Front Neurosci. 2017;11:529. doi: 10.3389/fnins.2017.00529</mixed-citation><mixed-citation xml:lang="en">Bednarik P, Moheet AA, Grohn H, et al. Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes. Front Neurosci. 2017;11:529. doi: 10.3389/fnins.2017.00529</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Hwang JJ, Parikh L, Lacadie C, et al. Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. J Clin Invest. 2018;128(4):1485-1495. doi: 10.1172/JCI97696</mixed-citation><mixed-citation xml:lang="en">Hwang JJ, Parikh L, Lacadie C, et al. Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. J Clin Invest. 2018;128(4):1485-1495. doi: 10.1172/JCI97696</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Mangia S, Tesfaye N, De Martino F, et al. Hypoglycemia-induced increases in thalamic cerebral blood flow are blunted in subjects with type 1 diabetes and hypoglycemia unawareness. J Cereb Blood Flow Metab. 2012;32(11):2084-2090. doi: 10.1038/jcbfm.2012.117</mixed-citation><mixed-citation xml:lang="en">Mangia S, Tesfaye N, De Martino F, et al. Hypoglycemia-induced increases in thalamic cerebral blood flow are blunted in subjects with type 1 diabetes and hypoglycemia unawareness. J Cereb Blood Flow Metab. 2012;32(11):2084-2090. doi: 10.1038/jcbfm.2012.117</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Wiegers EC, Becker KM, Rooijackers HM, et al. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. J Cereb Blood Flow Metab. 2017;37(6):1994-2001. doi: 10.1177/0271678X16658914</mixed-citation><mixed-citation xml:lang="en">Wiegers EC, Becker KM, Rooijackers HM, et al. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. J Cereb Blood Flow Metab. 2017;37(6):1994-2001. doi: 10.1177/0271678X16658914</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Dunn JT, Cranston I, Marsden PK, et al. Attenuation of amydgala and frontal cortical responses to low blood glucose concentration in asymptomatic hypoglycemia in type 1 diabetes: a new player in hypoglycemia unawareness? Diabetes. 2007;56(11):2766-2773. doi: 10.2337/db07-0666</mixed-citation><mixed-citation xml:lang="en">Dunn JT, Cranston I, Marsden PK, et al. Attenuation of amydgala and frontal cortical responses to low blood glucose concentration in asymptomatic hypoglycemia in type 1 diabetes: a new player in hypoglycemia unawareness? Diabetes. 2007;56(11):2766-2773. doi: 10.2337/db07-0666</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Bingham EM, Dunn JT, Smith D, et al. Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-D-glucose PET study. Diabetologia. 2005;48(10):2080-2089. doi: 10.1007/s00125-005-1900-6</mixed-citation><mixed-citation xml:lang="en">Bingham EM, Dunn JT, Smith D, et al. Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-D-glucose PET study. Diabetologia. 2005;48(10):2080-2089. doi: 10.1007/s00125-005-1900-6</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Wiegers EC, Rooijackers HM, Tack CJ, et al. Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia. Diabetes. 2017;66(12):3105-3110. doi: 10.2337/db17-0794</mixed-citation><mixed-citation xml:lang="en">Wiegers EC, Rooijackers HM, Tack CJ, et al. Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia. Diabetes. 2017;66(12):3105-3110. doi: 10.2337/db17-0794</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Henriksen MM, Faerch L, Thorsteinsson B, Pedersen-Bjergaard U. Long-Term Prediction of Severe Hypoglycemia in Type 1 Diabetes: Is It Really Possible? J Diabetes Sci Technol. 2016;10(6):1230-1235. doi: 10.1177/1932296816664745</mixed-citation><mixed-citation xml:lang="en">Henriksen MM, Faerch L, Thorsteinsson B, Pedersen-Bjergaard U. Long-Term Prediction of Severe Hypoglycemia in Type 1 Diabetes: Is It Really Possible? J Diabetes Sci Technol. 2016;10(6):1230-1235. doi: 10.1177/1932296816664745</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Lawton J, Rankin D, Elliott J, et al. Experiences, views, and support needs of family members of people with hypoglycemia unawareness: interview study. Diabetes Care. 2014;37(1):109-115. doi: 10.2337/dc13-1154</mixed-citation><mixed-citation xml:lang="en">Lawton J, Rankin D, Elliott J, et al. Experiences, views, and support needs of family members of people with hypoglycemia unawareness: interview study. Diabetes Care. 2014;37(1):109-115. doi: 10.2337/dc13-1154</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Hansen TI, Olsen SE, Haferstrom ECD, et al. Cognitive deficits associated with impaired awareness of hypoglycaemia in type 1 diabetes. Diabetologia. 2017;60(6):971-979. doi: 10.1007/s00125-017-4233-3</mixed-citation><mixed-citation xml:lang="en">Hansen TI, Olsen SE, Haferstrom ECD, et al. Cognitive deficits associated with impaired awareness of hypoglycaemia in type 1 diabetes. Diabetologia. 2017;60(6):971-979. doi: 10.1007/s00125-017-4233-3</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Little SA, Leelarathna L, Walkinshaw E, et al. Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS). Diabetes Care. 2014;37(8):2114-2122. doi: 10.2337/dc14-0030</mixed-citation><mixed-citation xml:lang="en">Little SA, Leelarathna L, Walkinshaw E, et al. Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS). Diabetes Care. 2014;37(8):2114-2122. doi: 10.2337/dc14-0030</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Leelarathna L, Little SA, Walkinshaw E, et al. Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial. Diabetes Care. 2013;36(12):4063-4070. doi: 10.2337/dc13-1004</mixed-citation><mixed-citation xml:lang="en">Leelarathna L, Little SA, Walkinshaw E, et al. Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial. Diabetes Care. 2013;36(12):4063-4070. doi: 10.2337/dc13-1004</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Little S, Chadwick T, Choudhary P, et al. Comparison of Optimised MDI versus Pumps with or without Sensors in Severe Hypoglycaemia (the Hypo COMPaSS trial). BMC Endocr Disord. 2012;12:33. doi: 10.1186/1472-6823-12-33</mixed-citation><mixed-citation xml:lang="en">Little S, Chadwick T, Choudhary P, et al. Comparison of Optimised MDI versus Pumps with or without Sensors in Severe Hypoglycaemia (the Hypo COMPaSS trial). BMC Endocr Disord. 2012;12:33. doi: 10.1186/1472-6823-12-33</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Shuttlewood E, De Zoysa N, Rankin D, Amiel S. A qualitative evaluation of DAFNE-HART: A psychoeducational programme to restore hypoglycaemia awareness. Diabetes Res Clin Pract. 2015;109(2):347-354. doi: 10.1016/j.diabres.2015.05.034</mixed-citation><mixed-citation xml:lang="en">Shuttlewood E, De Zoysa N, Rankin D, Amiel S. A qualitative evaluation of DAFNE-HART: A psychoeducational programme to restore hypoglycaemia awareness. Diabetes Res Clin Pract. 2015;109(2):347-354. doi: 10.1016/j.diabres.2015.05.034</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Rondags SM, de Wit M, Snoek FJ. HypoAware: development and pilot study of a brief and partly web-based psychoeducational group intervention for adults with Type 1 and insulin-treated Type 2 diabetes and problematic hypoglycaemia. Diabet Med. 2016;33(2):184-191. doi: 10.1111/dme.12876</mixed-citation><mixed-citation xml:lang="en">Rondags SM, de Wit M, Snoek FJ. HypoAware: development and pilot study of a brief and partly web-based psychoeducational group intervention for adults with Type 1 and insulin-treated Type 2 diabetes and problematic hypoglycaemia. Diabet Med. 2016;33(2):184-191. doi: 10.1111/dme.12876</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Rondags SMPA, de Wit M, Twisk JW, Snoek FJ. Effectiveness of HypoAware, a Brief Partly Web-Based Psychoeducational Intervention for Adults With Type 1 and Insulin-Treated Type 2 Diabetes and Problematic Hypoglycemia: A Cluster Randomized Controlled Trial. Diabetes Care. 2016;39(12):2190-2196. doi: 10.2337/dc16-1614</mixed-citation><mixed-citation xml:lang="en">Rondags SMPA, de Wit M, Twisk JW, Snoek FJ. Effectiveness of HypoAware, a Brief Partly Web-Based Psychoeducational Intervention for Adults With Type 1 and Insulin-Treated Type 2 Diabetes and Problematic Hypoglycemia: A Cluster Randomized Controlled Trial. Diabetes Care. 2016;39(12):2190-2196. doi: 10.2337/dc16-1614</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med. 2008;25(7):765-774. doi: 10.1111/j.1464-5491.2008.02486.x</mixed-citation><mixed-citation xml:lang="en">Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med. 2008;25(7):765-774. doi: 10.1111/j.1464-5491.2008.02486.x</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Шестакова М.В., Майоров А.Ю., Филиппов Ю.И., и др. Федеральные клинические рекомендации по помповой инсулинотерапии и непрерывному мониторингу гликемии у больных сахарным диабетом. Проект // Проблемы эндокринологии. — 2015. — Т. 61. — №6. — С. 55-78. [Shestakova MV, Mayorov AY, Philippov YI, et al. Russian national guidelines on insulin pump therapy and continuous glucose monitoring for diabetes mellitus patients. Draft. Problems of endocrinology. 2015;61(6):55-78. (In Russ.)] doi: 10.14341/probl201561655-78</mixed-citation><mixed-citation xml:lang="en">Шестакова М.В., Майоров А.Ю., Филиппов Ю.И., и др. Федеральные клинические рекомендации по помповой инсулинотерапии и непрерывному мониторингу гликемии у больных сахарным диабетом. Проект // Проблемы эндокринологии. — 2015. — Т. 61. — №6. — С. 55-78. [Shestakova MV, Mayorov AY, Philippov YI, et al. Russian national guidelines on insulin pump therapy and continuous glucose monitoring for diabetes mellitus patients. Draft. Problems of endocrinology. 2015;61(6):55-78. (In Russ.)] doi: 10.14341/probl201561655-78</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Battelino T, Conget I, Olsen B, et al.; SWITCH Study Group. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia. 2012;55(12):3155-3162. doi: 10.1007/s00125-012-2708-9</mixed-citation><mixed-citation xml:lang="en">Battelino T, Conget I, Olsen B, et al.; SWITCH Study Group. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia. 2012;55(12):3155-3162. doi: 10.1007/s00125-012-2708-9</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">van Beers CA, DeVries JH, Kleijer SJ, et al. Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial. Lancet Diabetes Endocrinol. 2016;4(11):893-902. doi: 10.1016/S2213-8587(16)30193-0</mixed-citation><mixed-citation xml:lang="en">van Beers CA, DeVries JH, Kleijer SJ, et al. Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial. Lancet Diabetes Endocrinol. 2016;4(11):893-902. doi: 10.1016/S2213-8587(16)30193-0</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Choudhary P, Ramasamy S, Green L, et al. Real-time continuous glucose monitoring significantly reduces severe hypoglycemia in hypoglycemia-unaware patients with type 1 diabetes. Diabetes Care. 2013;36(12):4160-4162. doi: 10.2337/dc13-0939</mixed-citation><mixed-citation xml:lang="en">Choudhary P, Ramasamy S, Green L, et al. Real-time continuous glucose monitoring significantly reduces severe hypoglycemia in hypoglycemia-unaware patients with type 1 diabetes. Diabetes Care. 2013;36(12):4160-4162. doi: 10.2337/dc13-0939</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Rickels MR, Peleckis AJ, Dalton-Bakes C, et al. Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes. J Clin Endocrinol Metab. 2018;103(1):105-114. doi: 10.1210/jc.2017-01516</mixed-citation><mixed-citation xml:lang="en">Rickels MR, Peleckis AJ, Dalton-Bakes C, et al. Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes. J Clin Endocrinol Metab. 2018;103(1):105-114. doi: 10.1210/jc.2017-01516</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Reddy M, Jugnee N, El Laboudi A, et al. A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with Type 1 diabetes and impaired awareness of hypoglycaemia. Diabet Med. 2018;35(4):483-490. doi: 10.1111/dme.13561</mixed-citation><mixed-citation xml:lang="en">Reddy M, Jugnee N, El Laboudi A, et al. A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with Type 1 diabetes and impaired awareness of hypoglycaemia. Diabet Med. 2018;35(4):483-490. doi: 10.1111/dme.13561</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Abitbol A, Rabasa-Lhoret R, Messier V, et al. Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial. Diabetes Technol Ther. 2018;20(3):189-196. doi: 10.1089/dia.2017.0353</mixed-citation><mixed-citation xml:lang="en">Abitbol A, Rabasa-Lhoret R, Messier V, et al. Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial. Diabetes Technol Ther. 2018;20(3):189-196. doi: 10.1089/dia.2017.0353</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Kamel JT, Goodman DJ, Howe K, et al. Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation. Diabetes Metab Res Rev. 2015;31(6):646-650. doi: 10.1002/dmrr.2652</mixed-citation><mixed-citation xml:lang="en">Kamel JT, Goodman DJ, Howe K, et al. Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation. Diabetes Metab Res Rev. 2015;31(6):646-650. doi: 10.1002/dmrr.2652</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Hering BJ, Clarke WR, Bridges ND, et al.; Clinical Islet Transplantation Consortium. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2016;39(7):1230-1240. doi: 10.2337/dc15-1988</mixed-citation><mixed-citation xml:lang="en">Hering BJ, Clarke WR, Bridges ND, et al.; Clinical Islet Transplantation Consortium. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2016;39(7):1230-1240. doi: 10.2337/dc15-1988</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Moheet A, Mangia S, Kumar A, et al. Naltrexone for treatment of impaired awareness of hypoglycemia in type 1 diabetes: A randomized clinical trial. J Diabetes Complications. 2015;29(8):1277-1282. doi: 10.1016/j.jdiacomp.2015.08.004</mixed-citation><mixed-citation xml:lang="en">Moheet A, Mangia S, Kumar A, et al. Naltrexone for treatment of impaired awareness of hypoglycemia in type 1 diabetes: A randomized clinical trial. J Diabetes Complications. 2015;29(8):1277-1282. doi: 10.1016/j.jdiacomp.2015.08.004</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Jin SM. Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions. Endocrinol Metab (Seoul). 2017;32(2):190-194. doi: 10.3803/EnM.2017.32.2.190</mixed-citation><mixed-citation xml:lang="en">Jin SM. Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions. Endocrinol Metab (Seoul). 2017;32(2):190-194. doi: 10.3803/EnM.2017.32.2.190</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Климонтов В.В., Циберкин А.И., Фазуллина О.Н. и др. Гипогликемии у пожилых больных сахарным диабетом 2 типа, получающих инсулин: результаты непрерывного мониторирования глюкозы // Сахарный диабет. — 2014. — Т. 17. — №1. — С. 75-80. [Klimontov VV, Tsiberkin AI, Fazullina ON, et al. Hypoglycemia in type 2 diabetes patients treated with insulin: the advantages of continuous glucose monitoring. Diabetes mellitus. 2014;17(1):75-80. (In Russ.)] doi: 10.14341/DM2014175-80</mixed-citation><mixed-citation xml:lang="en">Климонтов В.В., Циберкин А.И., Фазуллина О.Н. и др. Гипогликемии у пожилых больных сахарным диабетом 2 типа, получающих инсулин: результаты непрерывного мониторирования глюкозы // Сахарный диабет. — 2014. — Т. 17. — №1. — С. 75-80. [Klimontov VV, Tsiberkin AI, Fazullina ON, et al. Hypoglycemia in type 2 diabetes patients treated with insulin: the advantages of continuous glucose monitoring. Diabetes mellitus. 2014;17(1):75-80. (In Russ.)] doi: 10.14341/DM2014175-80</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang XW, Zhang XL, Xu B, Kang LN. Comparative safety and efficacy of insulin degludec with insulin glargine in type 2 and type 1 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):429-441. doi: 10.1007/s00592-018-1107-1</mixed-citation><mixed-citation xml:lang="en">Zhang XW, Zhang XL, Xu B, Kang LN. Comparative safety and efficacy of insulin degludec with insulin glargine in type 2 and type 1 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):429-441. doi: 10.1007/s00592-018-1107-1</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Ritzel R, Roussel R, Giaccari A, et al. Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes. Diabetes Obes Metab. 2018;20(3):541-548. doi: 10.1111/dom.13105</mixed-citation><mixed-citation xml:lang="en">Ritzel R, Roussel R, Giaccari A, et al. Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes. Diabetes Obes Metab. 2018;20(3):541-548. doi: 10.1111/dom.13105</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
