therapeuticЮжно-Российский журнал терапевтической практикиSouth Russian Journal of Therapeutic Practice2712-81563033-8344РостГМУ10.21886/2712-8156-2022-3-2-107-115therapeutic-253Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL CASESКлинический случай благоприятного течения неалкогольной жировой болезни печени у больного с сахарным диабетом 2 типаA clinical case of favorable course of non-alcoholic fatty liver disease with type 2 diabetes mellitushttps://orcid.org/0000-0001-7884-2433ВоробьёвС. В.VorobyovS. V.

Воробьёв Сергей Владиславович, д. м. н, проф., заведующий кафедрой эндокринологии с курсом детской эндокринологии

Ростов-на-Дону

Sergey V. Vorobyov, Dr. Sci. (Med.), Professor, Head of the Department of Endocrinology with the course of Pediatric Endocrinology

Rostov-on-Don

endocrinrostov@mail.ruhttps://orcid.org/0000-0001-9802-9810ИвановаА. А.IvanovaA. A.

Иванова Алина Андреевна, ординатор 1 года кафедры эндокринологии с курсом детской эндокринологии

Ростов-на-Дону

Alina A. Ivanova, 1-year resident of the Department of Endocrinology with the course of Pediatric Endocrinology

Rostov-on-Don

alya.an.ivanova@gmail.comhttps://orcid.org/0000-0001-5514-9978РассказоваМ. А.RasskazovaM. A.

Рассказова Мария Алексеевна, лаборант кафедры эндокринологии с курсом детской эндокринологии

Ростов-на-Дону

Maria A. Rasskazova, Laboratory assistant at the Department of Endocrinology with a course in Pediatric Endocrinology

Rostov-on-Don

mari.rasskazova.94@inbox.ruhttps://orcid.org/0000-0002-5054-8491СлюсаренкоД. А.SlyusarenkoD. A.

Слюсаренко Дарья Андреевна, лаборант кафедры эндокринологии с курсом детской эндокринологии

Ростов-на-Дону

Darya A. Slyusarenko, Laboratory assistant of the Department of Endocrinology with a course in pediatric Endocrinology

Rostov-on-Don

dslusarenko1997@gmail.comhttps://orcid.org/0000-0002-9466-0135ПетровскаяЕ. Ю.PetrovskayaE. Y.

Петровская Екатерина Юрьевна, к. м. н., ассистент кафедры эндокринологии с курсом детской эндокринологии

Ростов-на-Дону

Ekaterina Yu. Petrovskaya, PhD, Assistant of the Department of Endocrinology with the course of Pediatric Endocrinology

Rostov-on-Don

kate.rostov@mail.ruhttps://orcid.org/0000-0002-2767-4959КузьменкоН. А.KuzmenkoN. A.

Кузьменко Наталья Александровна, к. м. н., доцент кафедры эндокринологии с курсом детской эндокринологии

Ростов-на-Дону

Natalia A. Kuzmenko, PhD, Associate Professor of the Department of Endocrinology with the course of Pediatric Endocrinology

Rostov-on-Don

natalia-kuzmenko@yandex.ruФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава РоссииРоссияRostov State Medical UniversityRussian Federation20222606202232107115Copyright © Воробьёв С.В., Иванова А.А., Рассказова М.А., Слюсаренко Д.А., Петровская Е.Ю., Кузьменко Н.А., 20222022Воробьёв С.В., Иванова А.А., Рассказова М.А., Слюсаренко Д.А., Петровская Е.Ю., Кузьменко Н.А.Vorobyov S.V., Ivanova A.A., Rasskazova M.A., Slyusarenko D.A., Petrovskaya E.Y., Kuzmenko N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.therapeutic-j.ru/jour/article/view/253

Цель: обратить внимание клиницистов (терапевтов, эндокринологов, гастроэнтерологов) на проблему сахарного диабета 2 типа, сочетанного с неалкогольной жировой болезнью печени, для эффективной медикаментозной терапии, улучшения качества жизни и достижения комплаенса с данной категорией больных. Сахарный диабет 2 типа является нарушением углеводного обмена, обусловленным резистентностью к инсулину, протекающим с относительной инсулиновой недостаточностью либо без неё. Сахарный диабет 2 типа часто сочетается с определенными заболеваниями, одним из которых является неалкогольная жировая болезнь печени. Это накладывает определенные ограничения в терапии сахарного диабета 2 типа, которые необходимо учитывать при ведении таких больных. Понимание индивидуализированных рисков позволяет врачу сохранять настороженность в отношении данных пациентов. Комбинация эффективной медикаментозной терапии и коррекции образа жизни позволяет достичь значительного прогресса в терапии сахарного диабета 2 типа, сочетанного с неалкогольной жировой болезнью печени. Это позволяет улучшить качество жизни пациента и прогноз заболевания, а также избежать различных рисков и осложнений, которые могут привести к таким необратимым последствиям, как трансплантация печени.

We want to draw the attention of clinical therapists, endocrinologists and gastroenterologists to the problem of e⁄ective drug therapy for diabetes mellitus type 2 combined with non-alcoholic fatty liver disease, which can improve the life quality and achieve compliance with this category of patients. Type 2 diabetes mellitus is a carbohydrate metabolism disorder caused by insulin resistance, which may be accompanied by relative insulin de‹ciency or not. Type 2 diabetes mellitus is often combined with certain diseases, one of which is non-alcoholic fatty liver disease. This imposes certain limitations in the treatment of type 2 diabetes mellitus, which must be taken into account in order to maintain e⁄ective clinical managment. Understanding the genetically individualized risks allows the doctor to remain wary of these patients and treat them with the appropriate clinical methods. The combination of e⁄ective drug therapy and patient's awareness of the necessity for the lifestyle changes makes it possible to achieve signi‹cant improvements in the treatment of type 2 diabetes mellitus combined with non-alcoholic fatty liver disease. This treatment allows to improve the patient's life quality and prognosis of the disease as well as to avoid various risks and complications that can lead to irreversible consequences such as the need for liver transplantation.

сахарный диабет 2 типанеалкогольная жировая болезнь печенисахароснижающие препаратыжелчные кислотыинкретиныэссенциальные фосфолипидыtype 2 diabetes mellitusnon-alcoholic fatty liver diseaseantihyperglycemic drugsbile acidsincretinsessential phospholipidsReferencesPerumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(47):8263-8276. DOI: 10.3748/wjg.v23.i47.8263.Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(47):8263-8276. DOI: 10.3748/wjg.v23.i47.8263.Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020;21(17):6275. DOI: 10.3390/ijms21176275.Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020;21(17):6275. DOI: 10.3390/ijms21176275.European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402. DOI: 10.1016/j.jhep.2015.11.004.European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402. DOI: 10.1016/j.jhep.2015.11.004.Bril F, Cusi K. Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Call to Action. Diabetes Care. 2017;40(3):419-430. DOI: 10.2337/dc16-1787.Bril F, Cusi K. Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Call to Action. Diabetes Care. 2017;40(3):419-430. DOI: 10.2337/dc16-1787.Han E, Lee YH. Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases. Diabetes Metab J. 2017;41(6):430-437. DOI: 10.4093/dmj.2017.41.6.430.Han E, Lee YH. Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases. Diabetes Metab J. 2017;41(6):430-437. DOI: 10.4093/dmj.2017.41.6.430.Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. DOI: 10.1002/hep.29367.Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. DOI: 10.1002/hep.29367.Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-54. DOI: 10.1002/hep.27368.Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-54. DOI: 10.1002/hep.27368.Morling JR, Fallowfield JA, Guha IN, Nee LD, Glancy S, Williamson RM, et al. Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: the Edinburgh type 2 diabetes study. J Hepatol. 2014;60(2):384-91. DOI: 10.1016/j.jhep.2013.10.017.Morling JR, Fallowfield JA, Guha IN, Nee LD, Glancy S, Williamson RM, et al. Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: the Edinburgh type 2 diabetes study. J Hepatol. 2014;60(2):384-91. DOI: 10.1016/j.jhep.2013.10.017.Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. DOI: 10.1002/hep.28431.Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. DOI: 10.1002/hep.28431.Obika M, Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res. 2012;2012:145754. DOI: 10.1155/2012/145754.Obika M, Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res. 2012;2012:145754. DOI: 10.1155/2012/145754.Kumari M, Schoiswohl G, Chitraju C, Paar M, Cornaciu I, Rangrez AY, et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab. 2012;15(5):691-702. DOI: 10.1016/j.cmet.2012.04.008.Kumari M, Schoiswohl G, Chitraju C, Paar M, Cornaciu I, Rangrez AY, et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab. 2012;15(5):691-702. DOI: 10.1016/j.cmet.2012.04.008.Pingitore P, Pirazzi C, Mancina RM, Motta BM, Indiveri C, Pujia A, et al. Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function. Biochim Biophys Acta. 2014;1841(4):574-80. DOI: 10.1016/j.bbalip.2013.12.006.Pingitore P, Pirazzi C, Mancina RM, Motta BM, Indiveri C, Pujia A, et al. Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function. Biochim Biophys Acta. 2014;1841(4):574-80. DOI: 10.1016/j.bbalip.2013.12.006.Lee M, Kim KJ, Chung TH, Bae J, Lee YH, Lee BW, et al. Nonalcoholic fatty liver disease, diastolic dysfunction, and impaired myocardial glucose uptake in patients with type 2 diabetes. Diabetes Obes Metab. 2021;23(4):1041-1051. DOI: 10.1111/dom.14310.Lee M, Kim KJ, Chung TH, Bae J, Lee YH, Lee BW, et al. Nonalcoholic fatty liver disease, diastolic dysfunction, and impaired myocardial glucose uptake in patients with type 2 diabetes. Diabetes Obes Metab. 2021;23(4):1041-1051. DOI: 10.1111/dom.14310.Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142(4):711-725.e6. DOI: 10.1053/j.gastro.2012.02.003.Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142(4):711-725.e6. DOI: 10.1053/j.gastro.2012.02.003.Zhang L, Huang X, Meng Z, Dong B, Shiah S, Moore DD, et al. Significance and mechanism of CYP7a1 gene regulation during the acute phase of liver regeneration. Mol Endocrinol. 2009;23(2):137-45. DOI: 10.1210/me.2008-0198.Zhang L, Huang X, Meng Z, Dong B, Shiah S, Moore DD, et al. Significance and mechanism of CYP7a1 gene regulation during the acute phase of liver regeneration. Mol Endocrinol. 2009;23(2):137-45. DOI: 10.1210/me.2008-0198.McGlone ER, Bloom SR. Bile acids and the metabolic syndrome. Ann Clin Biochem. 2019;56(3):326-337. DOI: 10.1177/0004563218817798.McGlone ER, Bloom SR. Bile acids and the metabolic syndrome. Ann Clin Biochem. 2019;56(3):326-337. DOI: 10.1177/0004563218817798.Chiang JY. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol. 2004;40(3):539-51. DOI: 10.1016/j.jhep.2003.11.006.Chiang JY. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol. 2004;40(3):539-51. DOI: 10.1016/j.jhep.2003.11.006.Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjærg-Hansen A, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46(4):352-6. DOI: 10.1038/ng.2901.Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjærg-Hansen A, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46(4):352-6. DOI: 10.1038/ng.2901.Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137-74. DOI: 10.1146/annurev.biochem.72.121801.161712.Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137-74. DOI: 10.1146/annurev.biochem.72.121801.161712.Hofmann AF, Hagey LR, Krasowski MD. Bile salts of vertebrates: structural variation and possible evolutionary significance. J Lipid Res. 2010;51(2):226-46. DOI: 10.1194/jlr.R000042.Hofmann AF, Hagey LR, Krasowski MD. Bile salts of vertebrates: structural variation and possible evolutionary significance. J Lipid Res. 2010;51(2):226-46. DOI: 10.1194/jlr.R000042.Zhang M, Chiang JY. Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression. J Biol Chem. 2001;276(45):41690-9. DOI: 10.1074/jbc.M105117200.Zhang M, Chiang JY. Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression. J Biol Chem. 2001;276(45):41690-9. DOI: 10.1074/jbc.M105117200.Duane WC, Javitt NB. 27-hydroxycholesterol: production rates in normal human subjects. J Lipid Res. 1999;40(7):1194-9. PMID: 10393204.Duane WC, Javitt NB. 27-hydroxycholesterol: production rates in normal human subjects. J Lipid Res. 1999;40(7):1194-9. PMID: 10393204.Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65(16):2461-83. DOI: 10.1007/s00018-008-7568-6.Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65(16):2461-83. DOI: 10.1007/s00018-008-7568-6.Mooranian A, Negrulj R, Arfuso F, Al-Salami H. The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study. Drug Deliv Transl Res. 2015;5(5):511-22. DOI: 10.1007/s13346-015-0248-9. PMID: 26242686.Mooranian A, Negrulj R, Arfuso F, Al-Salami H. The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study. Drug Deliv Transl Res. 2015;5(5):511-22. DOI: 10.1007/s13346-015-0248-9. PMID: 26242686.Beglinger C, Hildebrand P, Adler G, Werth B, Luo H, Delco F, et al. Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man. Eur J Clin Invest. 1992;22(12):827-34. DOI: 10.1111/j.1365-2362.1992.tb01453.x.Beglinger C, Hildebrand P, Adler G, Werth B, Luo H, Delco F, et al. Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man. Eur J Clin Invest. 1992;22(12):827-34. DOI: 10.1111/j.1365-2362.1992.tb01453.x.Chen YS, Liu HM, Lee TY. Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice. Cells. 2019;8(3):253. DOI: 10.3390/cells8030253.Chen YS, Liu HM, Lee TY. Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice. Cells. 2019;8(3):253. DOI: 10.3390/cells8030253.Molinaro A, Wahlstrom A, Marschall HU. Role of Bile Acids in Metabolic Control. Trends Endocrinol. Metab. 2018;29:31–41. DOI: 10.1016/j.tem.2017.11.002.Molinaro A, Wahlstrom A, Marschall HU. Role of Bile Acids in Metabolic Control. Trends Endocrinol. Metab. 2018;29:31–41. DOI: 10.1016/j.tem.2017.11.002.Tomkin GH, Owens D. Obesity diabetes and the role of bile acids in metabolism. J Transl Int Med. 2016;4(2):73-80. DOI: 10.1515/jtim-2016-0018.Tomkin GH, Owens D. Obesity diabetes and the role of bile acids in metabolism. J Transl Int Med. 2016;4(2):73-80. DOI: 10.1515/jtim-2016-0018.Ståhlberg D, Rudling M, Angelin B, Björkhem I, Forsell P, Nilsell K, et al. Hepatic cholesterol metabolism in human obesity. Hepatology. 1997;25(6):1447-50. DOI: 10.1002/hep.510250623. PMID: 9185766.Ståhlberg D, Rudling M, Angelin B, Björkhem I, Forsell P, Nilsell K, et al. Hepatic cholesterol metabolism in human obesity. Hepatology. 1997;25(6):1447-50. DOI: 10.1002/hep.510250623. PMID: 9185766.Nadinskaia M, Maevskaya M, Ivashkin V, Kodzoeva K, Pirogova I, Chesnokov E, et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959-975. DOI: 10.3748/wjg.v27.i10.959.Nadinskaia M, Maevskaya M, Ivashkin V, Kodzoeva K, Pirogova I, Chesnokov E, et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959-975. DOI: 10.3748/wjg.v27.i10.959.Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, nonalcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385(9972):956-65. DOI: 10.1016/S0140-6736(14)61933-4.Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, nonalcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385(9972):956-65. DOI: 10.1016/S0140-6736(14)61933-4.

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