diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12095diaendo-12095Research ArticleОбзорыReviewЛиподистрофии в местах инъекций инсулина: современные тренды в эпидемиологии, диагностике и профилактикеLipodystrophy at the insulin injection sites: current trends in epidemiology, diagnostics and preventionhttps://orcid.org/0000-0002-5407-8722КлимонтовВадим ВалерьевичKlimontovVadim V.

д.м.н., профессор РАН 

MD, PhD, Professor

klimontov@mail.ruhttps://orcid.org/0000-0002-5076-6296ЛазаревМихаил МихайловичLazarevMikhail M.

м.н.с.

MD, junior research associate

mmlazarev@mail.ruhttps://orcid.org/0000-0002-9293-4083ЛетягинАндрей ЮрьевичLetyaginAndrey Ju.

д.м.н., профессор

MD, PhD, Professor

letyagin-andrey@yandex.ruhttps://orcid.org/0000-0002-3774-026XБулумбаеваДинара МухтаровнаBulumbaevaDinara M.

м.н.с.

MD, junior research associate

dinar.ka@mail.ruhttps://orcid.org/0000-0002-4507-093XБгатоваНаталия ПетровнаBgatovaNatalia P.

д.б.н., профессор

PhD, Professor

n_bgatova@ngs.ruНаучно-исследовательский институт клинической и экспериментальной лимфологии – филиал «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияResearch Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian FederationНаучно-исследовательский институт клинической и экспериментальной лимфологии – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияResearch Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian Federation202026062020232161173Copyright © Климонтов В.В., Лазарев М.М., Летягин А.Ю., Булумбаева Д.М., Бгатова Н.П., 20202020Климонтов В.В., Лазарев М.М., Летягин А.Ю., Булумбаева Д.М., Бгатова Н.П.Klimontov V.V., Lazarev M.M., Letyagin A.J., Bulumbaeva D.M., Bgatova N.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12095

Липодистрофии в местах инъекций – наиболее частое местное осложнение инсулинотерапии. История изучения осложнения началась в 1926 г., когда были описаны участки липоатрофии в местах введения инсулина. По мере перехода от животных инсулинов к инсулинам человека и к аналогам инсулина на смену иммуноопосредованной атрофической форме липодистрофии пришла гипертрофическая, связанная с анаболическим и митогенным ответом на инсулин.

При физикальном исследовании липогипертрофии в местах инъекций выявляются у 40–70% больных сахарным диабетом, получающих инсулин. Эффективность диагностики при этом зависит от навыков специалиста. В связи с этим представляется обоснованным обучение врачей и медицинских сестер методике осмотра и пальпации мест инъекций инсулина.

В последние годы для диагностики липогипертрофии стало применяться ультразвуковое исследование (УЗИ). Метод обладает большей чувствительностью в сравнении с пальпацией: верифицированные сонографически липогипертрофии выявляются более чем у 80% больных. У пациентов с распространенными зонами липогипертрофии УЗИ может использоваться для поиска оптимальных мест для инъекций («ультразвуковая карта мест инъекций»). Компрессионная соноэластография и объемное исследование кровотока в режиме энергетического допплеровского картирования позволяют дать количественную характеристику параметров жесткости и васкуляризации участков липогипертрофии. Перспективными методами диагностики являются магнитно-резонансная томография (МРТ) и инфракрасная термография.

В целом ряде исследований показано, что наличие липогипертрофии ассоциировано с ухудшением гликемического контроля: повышением уровня HbA1c и вариабельности гликемии, «необъяснимой» гипогликемией, увеличением доз инсулина. Тем самым, липогипертрофия повышает экономические затраты, связанные с сахарным диабетом.

Наиболее важным фактором риска развития индуцированной инсулином липогипертрофии является нарушение техники инъекций: недостаточная ротация мест инъекций, введение инсулина в участки липодистрофии, малая площадь зоны инъекций, редкая смена и избыточная длина игл. Обучение пациентов технике инъекций инсулина является основой профилактики данного осложнения. Прекращение инъекций в область липогипертрофии, регулярная ротация мест инъекций обеспечивают возможность адекватной титрации дозы инсулина и достижения целевого гликемического контроля.

Lipodystrophy at the injection sites is most common local complication of insulin therapy. The history of its study started in 1926, when first cases of lipoatrophy at the sites of insulin injections were described. As we moved to human insulin and insulin analogues, immune mediated atrophic form of lipodystrophy has been replaced by hypertrophic one, which reflects anabolic and mitogenic effect of insulin.

Lipohypertrophy at the injection sites is detected by physical examination in 40-70% of insulin-treated subjects. The detection efficiency depends on health care provider`s skills. Therefore, training of medical doctors and nurses in physical examination of injection sites seems to be reasonable.

In recent years, ultrasound was introduced for diagnostics of insulin-induced lipohypertrophy. The method is more sensitive compared to palpation; ultrasound-verified lipohypertropthy was detected in more than 80% of cases. In patients with wide-spread lipohypertrophy ultrasound can be used to find suitable sites for injections (“ultrasound injection map”). Strain sonoelastography and 3D-power Doppler ultrasound can be used for quantitative estimation of rigidity and vascularization of lipohypertrophy. Both MRI and infrared images are considered as promising diagnostic tools.

In a number of studies, it has been shown that the presence of lipohypertrophy is associated with high HbA1c levels, enhanced glycemic variability, «unexplained» hypoglycemia, and increased insulin doses. Thereby, lipohypertrophy aggravates the diabetes-related costs.

The main risk factor for lipohypertrophy is inappropriate injection technique, including the lack of the site rotation, injections into lipodystrophic lesions, small injection area, reuse or excessive length of the needles. Accordingly, training patients in the injection technique is the basis for prevention of complication. The cessation of injections in lipohypertrophy areas and regular site rotation is essential for adequate titration of insulin dose and achievement of glycemic targets.

сахарный диабетинсулининъекцииподкожная жировая клетчаткалиподистрофияультразвуковое исследованиеdiabetes mellitusinsulininjectionssubcutaneous tissuelipodystrophyultrasonographyReferencesBarborka CJ. Fatty atrophy from injections of insulin. Report of two cases. JAMA 1926;87(20):1646–1647. doi: https://doi.org/10.1001/jama.1926.92680200003012cBarborka CJ. Fatty atrophy from injections of insulin. Report of two cases. JAMA 1926;87(20):1646–1647. doi: https://doi.org/10.1001/jama.1926.92680200003012cDepisch F. Über lokale lipodystrophie bei lange zeit mit insulin behandelten fllen von diabetes. Klin Wehnschr. 1926;5(42):1965–1966. doi: https://doi.org/10.1007/bf01710208Depisch F. Über lokale lipodystrophie bei lange zeit mit insulin behandelten fllen von diabetes. Klin Wehnschr. 1926;5(42):1965–1966. doi: https://doi.org/10.1007/bf01710208Renold AE, Marble A, Fawcett DW. Action of insulin on deposition of glycogen and storage of fat in adipose tissue. Endocrinology. 1950;46(1):55–66. doi: https://doi.org/10.1210/endo-46-1-55Renold AE, Marble A, Fawcett DW. Action of insulin on deposition of glycogen and storage of fat in adipose tissue. Endocrinology. 1950;46(1):55–66. doi: https://doi.org/10.1210/endo-46-1-55Reeves WG, Allen BR, Tattersall RB. Insulin-induced lipoatrophy: evidence for an immune pathogenesis. BMJ. 1980;280(6230):1500–1503. doi: https://doi.org/10.1136/bmj.280.6230.1500Reeves WG, Allen BR, Tattersall RB. Insulin-induced lipoatrophy: evidence for an immune pathogenesis. BMJ. 1980;280(6230):1500–1503. doi: https://doi.org/10.1136/bmj.280.6230.1500Campbell IW, Duncan C, Anani AR. Paradoxical lipodystrophic changes due to conventional bovine and highly purified porcine/bovine insulins. Postgrad Med J. 1984;60(704):439–441. doi: https://doi.org/10.1136/pgmj.60.704.439Campbell IW, Duncan C, Anani AR. Paradoxical lipodystrophic changes due to conventional bovine and highly purified porcine/bovine insulins. Postgrad Med J. 1984;60(704):439–441. doi: https://doi.org/10.1136/pgmj.60.704.439Kordonouri O, Biester T, Schnell K, et al. Lipoatrophy in children with type 1 diabetes: an increasing incidence? J Diabetes Sci Technol. 2015;9(2):206–208. doi: https://doi.org/10.1177/1932296814558348Kordonouri O, Biester T, Schnell K, et al. Lipoatrophy in children with type 1 diabetes: an increasing incidence? J Diabetes Sci Technol. 2015;9(2):206–208. doi: https://doi.org/10.1177/1932296814558348Gentile S, Guarino G, Giancaterini A, et al. A suitable palpation technique allows to identify skin lipohypertrophic lesions in insulin-treated people with diabetes. Springerplus. 2016;5(1):563. doi: https://doi.org/10.1186/s40064-016-1978-yGentile S, Guarino G, Giancaterini A, et al. A suitable palpation technique allows to identify skin lipohypertrophic lesions in insulin-treated people with diabetes. Springerplus. 2016;5(1):563. doi: https://doi.org/10.1186/s40064-016-1978-yVardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007;77(2):231–236. doi: https://doi.org/10.1016/j.diabres.2006.12.023Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007;77(2):231–236. doi: https://doi.org/10.1016/j.diabres.2006.12.023Blanco M, Hernández MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39(5):445–453. doi: https://doi.org/10.1016/j.diabet.2013.05.006Blanco M, Hernández MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39(5):445–453. doi: https://doi.org/10.1016/j.diabet.2013.05.006Al Ajlouni M, Abujbara M, Batieha A, Ajlouni K. Prevalence of lipohypertrophy and associated risk factors in insulin-treated patients with type 2 diabetes mellitus. Int J Endocrinol Metab. 2015;13(2):e20776. doi: https://doi.org/10.5812/ijem.20776Al Ajlouni M, Abujbara M, Batieha A, Ajlouni K. Prevalence of lipohypertrophy and associated risk factors in insulin-treated patients with type 2 diabetes mellitus. Int J Endocrinol Metab. 2015;13(2):e20776. doi: https://doi.org/10.5812/ijem.20776Al Hayek AA, Robert AA, Braham RB, Al Dawish MA. Frequency of lipohypertrophy and associated risk factors in young patients with type 1 diabetes: a cross-sectional study. Diabetes Ther. 2016;7(2):259–267. doi: https://doi.org/10.1007/s13300-016-0161-3Al Hayek AA, Robert AA, Braham RB, Al Dawish MA. Frequency of lipohypertrophy and associated risk factors in young patients with type 1 diabetes: a cross-sectional study. Diabetes Ther. 2016;7(2):259–267. doi: https://doi.org/10.1007/s13300-016-0161-3Ji L, Sun Z, Li Q, et al. Lipohypertrophy in China: prevalence, risk factors, insulin consumption, and clinical impact. Diabetes Technol Ther. 2017;19(1):61–67. doi: https://doi.org/10.1089/dia.2016.0334Ji L, Sun Z, Li Q, et al. Lipohypertrophy in China: prevalence, risk factors, insulin consumption, and clinical impact. Diabetes Technol Ther. 2017;19(1):61–67. doi: https://doi.org/10.1089/dia.2016.0334Barola A, Tiwari P, Bhansali A, et al. Insulin-related lipohypertrophy: lipogenic action or tissue trauma? Front Endocrinol (Lausanne). 2018;9:638. doi: https://doi.org/10.3389/fendo.2018.00638Barola A, Tiwari P, Bhansali A, et al. Insulin-related lipohypertrophy: lipogenic action or tissue trauma? Front Endocrinol (Lausanne). 2018;9:638. doi: https://doi.org/10.3389/fendo.2018.00638Gupta SS, Gupta KS, Gathe SS, et al. Clinical implications of lipohypertrophy among people with type 1 diabetes in India. Diabetes Technol Ther. 2018;20(7):483–491. doi: https://doi.org/10.1089/dia.2018.0074Gupta SS, Gupta KS, Gathe SS, et al. Clinical implications of lipohypertrophy among people with type 1 diabetes in India. Diabetes Technol Ther. 2018;20(7):483–491. doi: https://doi.org/10.1089/dia.2018.0074Sürücü HA, O’Kur Arslan H. Lipohypertrophy in individuals with type 2 diabetes: prevalence and risk factors. J Caring Sci. 2018;7(2):67–74. doi: https://doi.org/10.15171/jcs.2018.011Sürücü HA, O’Kur Arslan H. Lipohypertrophy in individuals with type 2 diabetes: prevalence and risk factors. J Caring Sci. 2018;7(2):67–74. doi: https://doi.org/10.15171/jcs.2018.011Tsadik AG, Atey TM, Nedi T, et al. Effect of insulin-induced lipodystrophy on glycemic control among children and adolescents with diabetes in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. J Diabetes Res. 2018;2018:4910962. doi: https://doi.org/10.1155/2018/4910962Tsadik AG, Atey TM, Nedi T, et al. Effect of insulin-induced lipodystrophy on glycemic control among children and adolescents with diabetes in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. J Diabetes Res. 2018;2018:4910962. doi: https://doi.org/10.1155/2018/4910962Gentile S, Strollo F, Satta E, et al. Insulin-related lipohypertrophy in hemodialyzed diabetic people: a multicenter observational study and a methodological approach. Diabetes Ther. 2019;10(4):1423–1433. doi: https://doi.org/10.1007/s13300-019-0650-2Gentile S, Strollo F, Satta E, et al. Insulin-related lipohypertrophy in hemodialyzed diabetic people: a multicenter observational study and a methodological approach. Diabetes Ther. 2019;10(4):1423–1433. doi: https://doi.org/10.1007/s13300-019-0650-2Kordonouri O, Lauterborn R, Deiss D. Lipohypertrophy in young patients with type 1 diabetes. Diabetes Care. 2002;25(3):634. doi: https://doi.org/10.2337/diacare.25.3.634Kordonouri O, Lauterborn R, Deiss D. Lipohypertrophy in young patients with type 1 diabetes. Diabetes Care. 2002;25(3):634. doi: https://doi.org/10.2337/diacare.25.3.634Климонтов В.В., Лазарев М.М., Махотин А.А., и др. Липогипертрофии, индуцированные инсулином: клиническая и ультразвуковая характеристика // Сахарный диабет. — 2018. — Т. 21. — №4. — С. 255–263. [Klimontov VV, Lazarev MM, Makhotin AA, et al. Insulin-induced lipohypertrophy: clinical and ultrasound characteristics. Diabetes mellitus. 2018;21(4):255–263. (In Russ.)] doi: https://doi.org/10.14341/DM9549Климонтов В.В., Лазарев М.М., Махотин А.А., и др. Липогипертрофии, индуцированные инсулином: клиническая и ультразвуковая характеристика // Сахарный диабет. — 2018. — Т. 21. — №4. — С. 255–263. [Klimontov VV, Lazarev MM, Makhotin AA, et al. Insulin-induced lipohypertrophy: clinical and ultrasound characteristics. Diabetes mellitus. 2018;21(4):255–263. (In Russ.)] doi: https://doi.org/10.14341/DM9549Holstein A, Stege H, Kovacs P. Lipoatrophy associated with the use of insulin analogues: a new case associated with the use of insulin glargine and review of the literature. Expert Opin Drug Saf. 2010;9(2):225–231. doi: https://doi.org/10.1517/14740330903496402Holstein A, Stege H, Kovacs P. Lipoatrophy associated with the use of insulin analogues: a new case associated with the use of insulin glargine and review of the literature. Expert Opin Drug Saf. 2010;9(2):225–231. doi: https://doi.org/10.1517/14740330903496402Hernar I, Haltbakk J, Broström A. Differences in depression, treatment satisfaction and injection behaviour in adults with type 1 diabetes and different degrees of lipohypertrophy. J Clin Nurs. 2017;26(23-24):4583–4596. doi: https://doi.org/10.1111/jocn.13801Hernar I, Haltbakk J, Broström A. Differences in depression, treatment satisfaction and injection behaviour in adults with type 1 diabetes and different degrees of lipohypertrophy. J Clin Nurs. 2017;26(23-24):4583–4596. doi: https://doi.org/10.1111/jocn.13801Deeb A, Abdelrahman L, Tomy M, et al. Impact of insulin injection and infusion routines on lipohypertrophy and glycemic control in children and adults with diabetes. Diabetes Ther. 2019;10(1):259–267. doi: https://doi.org/10.1007/s13300-018-0561-7Deeb A, Abdelrahman L, Tomy M, et al. Impact of insulin injection and infusion routines on lipohypertrophy and glycemic control in children and adults with diabetes. Diabetes Ther. 2019;10(1):259–267. doi: https://doi.org/10.1007/s13300-018-0561-7Singha A, Bhattarcharjee R, Ghosh S, et al. Concurrence of lipoatrophy and lipohypertrophy in children with type 1 diabetes using recombinant human insulin: two case reports. Clin Diabetes. 2016;34(1):51–53. doi: https://doi.org/10.2337/diaclin.34.1.51Singha A, Bhattarcharjee R, Ghosh S, et al. Concurrence of lipoatrophy and lipohypertrophy in children with type 1 diabetes using recombinant human insulin: two case reports. Clin Diabetes. 2016;34(1):51–53. doi: https://doi.org/10.2337/diaclin.34.1.51Chakraborty PP, Biswas SN. Distant site lipoatrophy: a rare complication of subcutaneous insulin therapy. Postgrad Med J. 2016;92(1083):57–58. doi: https://doi.org/10.1136/postgradmedj-2015-133639Chakraborty PP, Biswas SN. Distant site lipoatrophy: a rare complication of subcutaneous insulin therapy. Postgrad Med J. 2016;92(1083):57–58. doi: https://doi.org/10.1136/postgradmedj-2015-133639Deng N, Zhang X, Zhao F, et al. Prevalence of lipohypertrophy in insulin-treated diabetes patients: a systematic review and meta-analysis. J Diabetes Investig. 2017. doi: https://doi.org/10.1111/jdi.12742Deng N, Zhang X, Zhao F, et al. Prevalence of lipohypertrophy in insulin-treated diabetes patients: a systematic review and meta-analysis. J Diabetes Investig. 2017. doi: https://doi.org/10.1111/jdi.12742Lopez X, Castells M, Ricker A, et al. Human insulin analog--induced lipoatrophy. Diabetes Care. 2008;31(3):442–444. doi: https://doi.org/10.2337/dc07-1739Lopez X, Castells M, Ricker A, et al. Human insulin analog--induced lipoatrophy. Diabetes Care. 2008;31(3):442–444. doi: https://doi.org/10.2337/dc07-1739Fujikura J, Fujimoto M, Yasue S, et al. Insulin-induced lipohypertrophy: report of a case with histopathology. Endocr J. 2005;52(5):623–628. doi: https://doi.org/10.1507/endocrj.52.623Fujikura J, Fujimoto M, Yasue S, et al. Insulin-induced lipohypertrophy: report of a case with histopathology. Endocr J. 2005;52(5):623–628. doi: https://doi.org/10.1507/endocrj.52.623Wallymahmed ME, Littler P, Clegg C, et al. Nodules of fibrocollagenous scar tissue induced by subcutaneous insulin injections: a cause of poor diabetic control. Postgrad Med J. 2004;80(950):732–733. doi: https://doi.org/10.1136/pgmj.2004.019547Wallymahmed ME, Littler P, Clegg C, et al. Nodules of fibrocollagenous scar tissue induced by subcutaneous insulin injections: a cause of poor diabetic control. Postgrad Med J. 2004;80(950):732–733. doi: https://doi.org/10.1136/pgmj.2004.019547Bernárdez C, Schärer L, Molina-Ruiz AM, Requena L. Nodular amyloidosis at the sites of insulin injections. J Cutan Pathol. 2015;42(7):496–502. doi: https://doi.org/10.1111/cup.12501Bernárdez C, Schärer L, Molina-Ruiz AM, Requena L. Nodular amyloidosis at the sites of insulin injections. J Cutan Pathol. 2015;42(7):496–502. doi: https://doi.org/10.1111/cup.12501Landau S. Images in clinical medicine. Insulin-induced lipohypertrophy. N Engl J Med. 2012;366(5):e9. doi: https://doi.org/10.1056/NEJMicm1101527Landau S. Images in clinical medicine. Insulin-induced lipohypertrophy. N Engl J Med. 2012;366(5):e9. doi: https://doi.org/10.1056/NEJMicm1101527Strollo F, Guarino G, Armentano V, et al. Unexplained hypoglycaemia and large glycaemic variability: skin lipohypertrophy as a predictive sign. Diabetes Res Open J. 2016;2(1):24–32. doi: https://doi.org/10.17140/DROJ-2-126Strollo F, Guarino G, Armentano V, et al. Unexplained hypoglycaemia and large glycaemic variability: skin lipohypertrophy as a predictive sign. Diabetes Res Open J. 2016;2(1):24–32. doi: https://doi.org/10.17140/DROJ-2-126Omar MA, El-Kafoury AA, El-Araby RI. Lipohypertrophy in children and adolescents with type 1 diabetes and the associated factors. BMC Res Notes. 2011;4:290. doi: https://doi.org/10.1186/1756-0500-4-290Omar MA, El-Kafoury AA, El-Araby RI. Lipohypertrophy in children and adolescents with type 1 diabetes and the associated factors. BMC Res Notes. 2011;4:290. doi: https://doi.org/10.1186/1756-0500-4-290Sawatkar GU, Kanwar AJ, Dogra S, et al. Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 south asian patients. Br J Dermatol. 2014;171(6):1402–1406. doi: https://doi.org/10.1111/bjd.13077Sawatkar GU, Kanwar AJ, Dogra S, et al. Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 south asian patients. Br J Dermatol. 2014;171(6):1402–1406. doi: https://doi.org/10.1111/bjd.13077Лазарев М.М., Климонтов В.В., Летягин А.Ю., и др. Комплексная ультразвуковая диагностика липогипертрофий, индуцированных инсулином, у больных сахарным диабетом // Российский электронный журнал лучевой диагностики. — 2019. — Т. 9. — №3. — С. 143–154. [Lazarev MM, Klimontov VV, Letyagin AYu, et al. Complex ultrasound diagnostics of insulin-induced lipohypertropthy in patients with diabetes. Rossijskii jelektronnii zhurnal luchevoi diagnostiki. 2019;9(3):143–154. (In Russ).] doi: https://doi.org/10.21569/2222-7415-2019-9-3-143-154Лазарев М.М., Климонтов В.В., Летягин А.Ю., и др. Комплексная ультразвуковая диагностика липогипертрофий, индуцированных инсулином, у больных сахарным диабетом // Российский электронный журнал лучевой диагностики. — 2019. — Т. 9. — №3. — С. 143–154. [Lazarev MM, Klimontov VV, Letyagin AYu, et al. Complex ultrasound diagnostics of insulin-induced lipohypertropthy in patients with diabetes. Rossijskii jelektronnii zhurnal luchevoi diagnostiki. 2019;9(3):143–154. (In Russ).] doi: https://doi.org/10.21569/2222-7415-2019-9-3-143-154Волкова Н.И., Давиденко И.Ю. Клиническое значение липогипертрофий без визуальных и пальпаторных изменений, выявленных с помощью УЗИ подкожной жировой клетчатки // Терапевтический архив. — 2019. — Т. 91. — №4. —С. 62–66. [Volkova NI, Davidenko IY. Clinical significance of lipohypertrophy without visual and palpable changes detected by ultrasonography of subcutaneous fat. Ter arkh. 2019;91(4):62–66. (In Russ.)] doi: https://doi.org/10.26442/00403660.2019.04.000128Волкова Н.И., Давиденко И.Ю. Клиническое значение липогипертрофий без визуальных и пальпаторных изменений, выявленных с помощью УЗИ подкожной жировой клетчатки // Терапевтический архив. — 2019. — Т. 91. — №4. —С. 62–66. [Volkova NI, Davidenko IY. Clinical significance of lipohypertrophy without visual and palpable changes detected by ultrasonography of subcutaneous fat. Ter arkh. 2019;91(4):62–66. (In Russ.)] doi: https://doi.org/10.26442/00403660.2019.04.000128Abu Ghazaleh H, Hashem Р, Forbes A, et al. A Systematic review of ultrasound-detected lipohypertrophy in insulin-exposed people with diabetes. Diabetes Ther. 2018;9(5):1741–1756. doi: https://doi.org/10.1007/s13300-018-0472-7Abu Ghazaleh H, Hashem Р, Forbes A, et al. A Systematic review of ultrasound-detected lipohypertrophy in insulin-exposed people with diabetes. Diabetes Ther. 2018;9(5):1741–1756. doi: https://doi.org/10.1007/s13300-018-0472-7Volkova N, Davidenko I, Rudakova Ju, Sesukina A. Insulin-induced lipohypertrophy diagnostics in diabetic patients: subcutaneous fat ultrasonography. Endocrine Abstracts 2015:37:EP351. doi: https://doi.org/10.1530/endoabs.37.EP351Volkova N, Davidenko I, Rudakova Ju, Sesukina A. Insulin-induced lipohypertrophy diagnostics in diabetic patients: subcutaneous fat ultrasonography. Endocrine Abstracts 2015:37:EP351. doi: https://doi.org/10.1530/endoabs.37.EP351Kapeluto JE, Paty BW, Chang SD, Meneilly GS. Ultrasound detection of insulin-induced lipohypertrophy in type 1 and type 2 diabetes. Diabet Med. 2018;35(10):1383–1390. doi: https://doi.org/10.1111/dme.13764Kapeluto JE, Paty BW, Chang SD, Meneilly GS. Ultrasound detection of insulin-induced lipohypertrophy in type 1 and type 2 diabetes. Diabet Med. 2018;35(10):1383–1390. doi: https://doi.org/10.1111/dme.13764Perciun R. Ultrasonographic aspect of su bcutaneous tissue dystrophies as a result of insulin injections. Med Ultrasonogr. 2010;12(2):104–109Perciun R. Ultrasonographic aspect of su bcutaneous tissue dystrophies as a result of insulin injections. Med Ultrasonogr. 2010;12(2):104–109Mulnier H, Hashem R, Duaso M, et al. Subcutaneous tissue changes and dermal inflammation at insulin injections sites: a feasibility study using ultrasound to describe characterize and grade lipohypertrophy. Diabetologia. 2017;60(Suppl 1):S90.Mulnier H, Hashem R, Duaso M, et al. Subcutaneous tissue changes and dermal inflammation at insulin injections sites: a feasibility study using ultrasound to describe characterize and grade lipohypertrophy. Diabetologia. 2017;60(Suppl 1):S90.Bertuzzi F, Meneghini E, Bruschi E, et al. Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus. J Endocrinol Invest. 2017;40(10):1107–1113. doi: https://doi.org/10.1007/s40618-017-0675-1Bertuzzi F, Meneghini E, Bruschi E, et al. Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus. J Endocrinol Invest. 2017;40(10):1107–1113. doi: https://doi.org/10.1007/s40618-017-0675-1Kaltheuner L, Kaltheuner M, Heinemann L. Lipohypertrophic skin changes in patients with diabetes: visualization by infrared images. J Diabetes Sci Technol. 2018;12(6):1152–1158. doi: https://doi.org/10.1177/1932296818777264Kaltheuner L, Kaltheuner M, Heinemann L. Lipohypertrophic skin changes in patients with diabetes: visualization by infrared images. J Diabetes Sci Technol. 2018;12(6):1152–1158. doi: https://doi.org/10.1177/1932296818777264Gradel AK, Porsgaard T, Lykkesfeldt J, et al. Factors affecting the absorption of subcutaneously administered insulin: effect on variability. J Diabetes Res. 2018;2018:1205121. doi: https://doi.org/10.1155/2018/1205121Gradel AK, Porsgaard T, Lykkesfeldt J, et al. Factors affecting the absorption of subcutaneously administered insulin: effect on variability. J Diabetes Res. 2018;2018:1205121. doi: https://doi.org/10.1155/2018/1205121Famulla S, Hövelmann U, Fischer A, et al. Insulin injection into lipohypertrophic tissue: blunted and more variable insulin absorption and action and impaired postprandial glucose control. Diabetes Care. 2016;39(9):1486–1492. doi: https://doi.org/10.2337/dc16-0610Famulla S, Hövelmann U, Fischer A, et al. Insulin injection into lipohypertrophic tissue: blunted and more variable insulin absorption and action and impaired postprandial glucose control. Diabetes Care. 2016;39(9):1486–1492. doi: https://doi.org/10.2337/dc16-0610Климонтов В.В. Влияние вариабельности гликемии на риск развития сердечно-сосудистых осложнений при сахарном диабете // Кардиология. — 2018. — Т. 58. — №10. — С. 80–87. [Klimontov VV. Impact of glycemic variability on cardiovascular risk in diabetes. Cardiology. 2018;58(10):80–87. (In Russ.)] doi: https://doi.org/10.18087/cardio.2018.10.10152Климонтов В.В. Влияние вариабельности гликемии на риск развития сердечно-сосудистых осложнений при сахарном диабете // Кардиология. — 2018. — Т. 58. — №10. — С. 80–87. [Klimontov VV. Impact of glycemic variability on cardiovascular risk in diabetes. Cardiology. 2018;58(10):80–87. (In Russ.)] doi: https://doi.org/10.18087/cardio.2018.10.10152Klimontov 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: https://doi.org/10.1016/j.dsx.2016.08.023Klimontov 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: https://doi.org/10.1016/j.dsx.2016.08.023Майоров А.Ю., Мельникова О.Г., Котешкова О.М., и др. Техника инъекций и инфузии при лечении сахарного диабета. Методическое руководство. — М., 2018. — 64 с. [Mayorov AY, Melnikova OG, Koteshkova OM, et al. The technique of injection and infusion in the treatment of diabetes. Methodological guidance. Moscow; 2018. 64 р. (In Russ.)]Майоров А.Ю., Мельникова О.Г., Котешкова О.М., и др. Техника инъекций и инфузии при лечении сахарного диабета. Методическое руководство. — М., 2018. — 64 с. [Mayorov AY, Melnikova OG, Koteshkova OM, et al. The technique of injection and infusion in the treatment of diabetes. Methodological guidance. Moscow; 2018. 64 р. (In Russ.)]Smith M, Clapham L, Strauss K. UK lipohypertrophy interventional study. Diabetes Res Clin Pract. 2017;126:248–253. doi: https://doi.org/10.1016/j.diabres.2017.01.020Smith M, Clapham L, Strauss K. UK lipohypertrophy interventional study. Diabetes Res Clin Pract. 2017;126:248–253. doi: https://doi.org/10.1016/j.diabres.2017.01.020Samdal F, Amland PF, Sandsmark M, Birkeland KI. Diabetic lipohypertrophy treated with suction-assisted lipectomy. J Intern Med. 1993;234(5):489–492. doi: https://doi.org/10.1111/j.1365-2796.1993.tb00782.xSamdal F, Amland PF, Sandsmark M, Birkeland KI. Diabetic lipohypertrophy treated with suction-assisted lipectomy. J Intern Med. 1993;234(5):489–492. doi: https://doi.org/10.1111/j.1365-2796.1993.tb00782.xGandolfi E, Thione A. A case of insulin lipohypertrophy in a young diabetic female successfully treated by vibroliposuction. J Plast Reconstr Aesthet Surg. 2009;62(12):e601–603. doi: https://doi.org/10.1016/j.bjps.2008.11.114Gandolfi E, Thione A. A case of insulin lipohypertrophy in a young diabetic female successfully treated by vibroliposuction. J Plast Reconstr Aesthet Surg. 2009;62(12):e601–603. doi: https://doi.org/10.1016/j.bjps.2008.11.114RadiAnt DICOM Viewer [Software]. Version 5.0.0 [cited 2019 November 19]. Available from: https://www.radiantviewer.com/blog/RadiAnt DICOM Viewer [Software]. Version 5.0.0 [cited 2019 November 19]. Available from: https://www.radiantviewer.com/blog/

The authors declare that there are no conflicts of interest present.