Non-alcoholic fatty liver disease in type 1 diabetes: Prevalence and pathophysiology

Plator Memaj, François R Jornayvaz, Plator Memaj, François R Jornayvaz

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in the general population with a global prevalence of 25%. It is often associated with metabolic syndrome and type 2 diabetes, as insulin resistance and hyperinsulinemia are known to be favoring factors. Recent studies have described growing incidence of NAFLD in type 1 diabetes (T1D) as well. Although increasing prevalence of metabolic syndrome in these patients seems to explain part of this increase in NAFLD, other underlying mechanisms may participate in the emergence of NAFLD. Notably, some genetic factors are more associated with fatty liver disease, but their prevalence in T1D has not been evaluated. Moreover, oxidative stress, poor glucose control and long-lasting hyperglycemia, as well as exogenous insulin administration play an important role in intrahepatic fat homeostasis. The main differential diagnosis of NAFLD in T1D is glycogenic hepatopathy, which needs to be considered mostly in T1D patients with poor glycemic control. This article aims to review the prevalence and pathophysiology of NAFLD in T1D and open perspectives for clinicians taking care of T1D patients with potential hepatopathy.

Keywords: NAFLD; glycogenic hepatopathy; pathophysiology; prevalence; type 1 diabetes.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Memaj and Jornayvaz.

References

    1. Powell EE, Wong VWS, Rinella M. Non-alcoholic fatty liver disease. Lancet (2021) 397(10290):2212–24. doi: 10.1016/S0140-6736(20)32511-3
    1. Gariani K, Philippe J, Jornayvaz FR. Non-alcoholic fatty liver disease and insulin resistance: from bench to bedside. Diabetes Metab (2013) 39(1):16–26. doi: 10.1016/j.diabet.2012.11.002
    1. de Vries M, Westerink J, Kaasjager KHAH, de Valk HW. Prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes mellitus: A systematic review and meta-analysis. J Clin Endocrinol Metab (2020) 105(12):3842–53. doi: 10.1210/clinem/dgaa575
    1. Petit JM, Pedro L, Guiu B, Duvillard L, Bouillet B, Jooste V, et al. . Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis. Diabetes Med (2015) 32(12):1648–51. doi: 10.1111/dme.12805
    1. Shi Y, Wang Q, Sun Y, Zhao X, Kong Y, Ou X, et al. . The prevalence of Lean/Nonobese nonalcoholic fatty liver disease: A systematic review and meta-analysis. J Clin Gastroenterol (2020) 54(4):378–87. doi: 10.1097/MCG.0000000000001270
    1. Priya G, Kalra S. A review of insulin resistance in type 1 diabetes: Is there a place for adjunctive metformin? Diabetes Ther (2018) 9(1):349–61. doi: 10.1007/s13300-017-0333-9
    1. Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the global burden of chronic liver diseases from 2012 to 2017: The growing impact of NAFLD. Hepatology (2020) 72(5):1605–16. doi: 10.1002/hep.31173
    1. Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, et al. . The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol (2019) 71(4):793–801. doi: 10.1016/j.jhep.2019.06.021
    1. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism (2019) 92:82–97. doi: 10.1016/j.metabol.2018.11.014
    1. Kanwal F, Kramer JR, Li L, Dai J, Natarajan Y, Yu X, et al. . Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in nonalcoholic fatty liver disease. Hepatology (2020) 71(3):808–19. doi: 10.1002/hep.31014
    1. Liu Y, Zhong GC, Tan HY, Hao FB, Hu JJ. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis. Sci Rep (2019) 9(1):11124. doi: 10.1038/s41598-019-47687-3
    1. Wu S, Wu F, Ding Y, Hou J, Bi J, Zhang Z. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis. Sci Rep (2016) 6(1):33386. doi: 10.1038/srep33386
    1. Sanyal AJ, Banas C, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, et al. . Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis c. Hepatology (2006) 43(4):682–9. doi: 10.1002/hep.21103
    1. Kanwal F, Kramer JR, Mapakshi S, Natarajan Y, Chayanupatkul M, Richardson PA, et al. . Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease. Gastroenterology (2018) 155(6):1828–1837.e2. doi: 10.1053/j.gastro.2018.08.024
    1. Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut (2020) 69(9):1691–705. doi: 10.1136/gutjnl-2020-320622
    1. Syed FZ. Type 1 diabetes mellitus. Ann Intern Med (2022) 175(3):ITC33–48. doi: 10.7326/AITC202203150
    1. Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem (2011) 57(2):176–85. doi: 10.1373/clinchem.2010.148221
    1. Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. . Type 1 diabetes mellitus. Nat Rev Dis Primers (2017) 3:17016. doi: 10.1038/nrdp.2017.16
    1. Pyle L, Kelsey MM. Youth-onset type 2 diabetes: translating epidemiology into clinical trials. Diabetologia (2021) 64(8):1709–16. doi: 10.1007/s00125-021-05480-w
    1. Chiang JL, Kirkman MS, Laffel LMB, Peters AL, Type 1 Diabetes Sourcebook Authors . Type 1 diabetes through the life span: a position statement of the American diabetes association. Diabetes Care (2014) 37(7):2034–54. doi: 10.2337/dc14-1140
    1. Cotter TG, Rinella M. Nonalcoholic fatty liver disease 2020: The state of the disease. Gastroenterology (2020) 158(7):1851–64. doi: 10.1053/j.gastro.2020.01.052
    1. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. . Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology (2005) 41(6):1313–21. doi: 10.1002/hep.20701
    1. Mertens J, Van Gaal LF, Francque SM, De Block C. NAFLD in type 1 diabetes: overrated or underappreciated? Ther Adv Endocrinol Metab (2021) 12:20420188211055556. doi: 10.1177/20420188211055557
    1. Kinner S, Reeder SB, Yokoo T. Quantitative imaging biomarkers of NAFLD. Dig Dis Sci (2016) 61(5):1337–47. doi: 10.1007/s10620-016-4037-1
    1. Mertens J, De Block C, Spinhoven M, Driessen A, Francque SM, Kwanten WJ. Hepatopathy associated with type 1 diabetes: Distinguishing non-alcoholic fatty liver disease from glycogenic hepatopathy. Front Pharmacol (2021) 12:768576. doi: 10.3389/fphar.2021.768576
    1. Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E, et al. . Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology (2019) 69(6):2672–82. doi: 10.1002/hep.30251
    1. de Vries M, El-Morabit F, van Erpecum KJ, Westerink J, Bac ST, Kaasjager HAHK, et al. . Non-alcoholic fatty liver disease: identical etiologic factors in patients with type 1 and type 2 diabetes. Eur J Intern Med (2022) 100:77–82. doi: 10.1016/j.ejim.2022.03.025
    1. Gariani K, Jornayvaz FR. NAFLD: From mechanisms to therapeutic approaches. Biomedicines (2022) 10(7):1747. doi: 10.3390/biomedicines10071747
    1. Asrih M, Jornayvaz FR. Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link? Mol Cell Endocrinol (2015) 418 Pt 1:55–65. doi: 10.1016/j.mce.2015.02.018
    1. Asrih M, Jornayvaz FR. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J Endocrinol (2013) 218(3):R25–36. doi: 10.1530/JOE-13-0201
    1. Nascè A, Gariani K, Jornayvaz FR, Szanto I. NADPH oxidases connecting fatty liver disease, insulin resistance and type 2 diabetes: Current knowledge and therapeutic outlook. Antioxidants (Basel) (2022) 11(6):1131. doi: 10.3390/antiox11061131
    1. Delli Bovi AP, Marciano F, Mandato C, Siano MA, Savoia M, Vajro P. Oxidative stress in non-alcoholic fatty liver disease. Updated Mini Rev Front Med (2021) 8:595371. doi: 10.3389/fmed.2021.595371
    1. Shabalala SC, Dludla PV, Mabasa L, Kappo AP, Basson AK, Pheiffer C, et al. . The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. BioMed Pharmacother (2020) 131:110785. doi: 10.1016/j.biopha.2020.110785
    1. Bril F, Lomonaco R, Orsak B, Ortiz-Lopez C, Webb A, Tio F, et al. . Relationship between disease severity, hyperinsulinemia, and impaired insulin clearance in patients with nonalcoholic steatohepatitis. Hepatology (2014) 59(6):2178–87. doi: 10.1002/hep.26988
    1. Serdarova M, Dimova R, Chakarova N, Grozeva G, Todorova A, Tsarkova P, et al. . Metabolic determinants of NAFLD in adults with type 1 diabetes. Diabetes Res Clin Pract avr (2022) 186:109819. doi: 10.1016/j.diabres.2022.109819
    1. Najjar SM, Perdomo G. Hepatic insulin clearance: Mechanism and physiology. Physiol (Bethesda) (2019) 34(3):198–215. doi: 10.1152/physiol.00048.2018
    1. Rorsman P, Eliasson L, Renström E, Gromada J, Barg S, Göpel S. The cell physiology of biphasic insulin secretion. News Physiol Sci (2000) 15:72–7. doi: 10.1152/physiologyonline.2000.15.2.72
    1. Flatt JP. Use and storage of carbohydrate and fat. Am J Clin Nutr (1995) 61(4 Suppl):952S–9S. doi: 10.1093/ajcn/61.4.952S
    1. Regnell SE, Lernmark Å. Hepatic steatosis in type 1 diabetes. Rev Diabetes Stud (2011) 8(4):454–67. doi: 10.1900/RDS.2011.8.454
    1. Rojano-Toimil A, Rivera-Esteban J, Manzano-Nuñez R, Bañares J, Martinez Selva D, Gabriel-Medina P, et al. . When sugar reaches the liver: Phenotypes of patients with diabetes and NAFLD. J Clin Med (2022) 11(12):3286. doi: 10.3390/jcm11123286
    1. Dif N, Euthine V, Gonnet E, Laville M, Vidal H, Lefai E. Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs. Biochem J (2006) 400(1):179–88. doi: 10.1042/BJ20060499
    1. DeBose-Boyd RA, Ye J. SREBPs in lipid metabolism, insulin signaling, and beyond. Trends Biochem Sci (2018) 43(5):358–68. doi: 10.1016/j.tibs.2018.01.005
    1. Bertolio R, Napoletano F, Mano M, Maurer-Stroh S, Fantuz M, Zannini A, et al. . Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat Commun (2019) 10(1):1326. doi: 10.1038/s41467-019-09152-7
    1. Iizuka K, Horikawa Y. ChREBP: A glucose-activated transcription factor involved in the development of metabolic syndrome. Endocr J (2008) 55(4):617–24. doi: 10.1507/endocrj.K07E-110
    1. Roeb E, Weiskirchen R. Fructose and non-alcoholic steatohepatitis. Front Pharmacol (2021) 12:634344. doi: 10.3389/fphar.2021.634344
    1. Bumbu A, Moutairou A, Matar O, Fumeron F, Velho G, Riveline J, et al. . Non-severe hypoglycaemia is associated with weight gain in patients with type 1 diabetes: Results from the diabetes control and complication trial. Diabetes Obes Metab (2018) 20(5):1289–92. doi: 10.1111/dom.13197
    1. Unger RH, Orci L. Paracrinology of islets and the paracrinopathy of diabetes. Proc Natl Acad Sci USA (2010) 107(38):16009–12. doi: 10.1073/pnas.1006639107
    1. Fineman M, Weyer C, Maggs DG, Strobel S, Kolterman OG. The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus. Horm Metab Res (2002) 34(9):504–8. doi: 10.1055/s-2002-34790
    1. Galsgaard KD, Pedersen J, Knop FK, Holst JJ, Wewer Albrechtsen NJ. Glucagon receptor signaling and lipid metabolism. Front Physiol (2019) 10:413. doi: 10.3389/fphys.2019.00413
    1. Galsgaard KD. The vicious circle of hepatic glucagon resistance in non-alcoholic fatty liver disease. JCM (2020) 9(12):4049. doi: 10.3390/jcm9124049
    1. Mantovani A, Petracca G, Beatrice G, Csermely A, Lonardo A, Targher G. Glucagon-like peptide-1 receptor agonists for treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An updated meta-analysis of randomized controlled trials. Metabolites (2021) 11(2):73. doi: 10.3390/metabo11020073
    1. Zibar K, Ćuća JK, Blaslov K, Bulum T, Smirčić-Duvnjak L. Difference in glucagon-like peptide-1 concentrations between c-peptide negative type 1 diabetes mellitus patients and healthy controls. Ann Clin Biochem (2015) 52(Pt 2):220–5. doi: 10.1177/0004563214544709
    1. Blaslov K, Bulum T, Zibar K, Duvnjak L. Relationship between metabolic syndrome and meal-induced glucagon like peptide-1 response in type 1 diabetic patients1-1. J Diabetes (2015) 7(3):340–6. doi: 10.1111/1753-0407.12194
    1. Thivolet C, Marchand L, Chikh K. Inappropriate glucagon and GLP-1 secretion in individuals with long-standing type 1 diabetes: effects of residual c-peptide. Diabetologia (2019) 62(4):593–7. doi: 10.1007/s00125-018-4804-y
    1. Lugari R, Dell’Anna C, Ugolotti D, Dei Cas A, Barilli AL, Zandomeneghi R, et al. . Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes. Horm Metab Res (2000) 32(10):424–8. doi: 10.1055/s-2007-978665
    1. Vilsbøll T, Krarup T, Sonne J, Madsbad S, Vølund A, Juul AG, et al. . Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab (2003) 88(6):2706–13. doi: 10.1210/jc.2002-021873
    1. Madhu SV, Jain R, Kant S, Prakash V. Mauriac syndrome: A rare complication of type 1 diabetes mellitus. Indian J Endocrinol Metab (2013) 17(4):764–5. doi: 10.4103/2230-8210.113780
    1. Torbenson M, Chen YY, Brunt E, Cummings OW, Gottfried M, Jakate S, et al. . Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus. Am J Surg Pathol (2006) 30(4):508–13. doi: 10.1097/00000478-200604000-00012
    1. Sherigar JM, Castro JD, Yin YM, Guss D, Mohanty SR. Glycogenic hepatopathy: A narrative review. World J Hepatol (2018) 10(2):172–85. doi: 10.4254/wjh.v10.i2.172
    1. Saikusa M, Yatsuga S, Tonan T, Koga Y. Glycogenic hepatopathy and non-alcoholic fatty liver disease in type 1 diabetes patients. Pediatr Int (2013) 55(6):806–7. doi: 10.1111/ped.12235
    1. Harman DJ, Kaye PV, Harris R, Suzuki A, Gazis A, Aithal GP. Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes. Hepatology (2014) 60(1):158–68. doi: 10.1002/hep.27098
    1. Kupriyanova Y, Zaharia OP, Bobrov P, Karusheva Y, Burkart V, Szendroedi J, et al. . Early changes in hepatic energy metabolism and lipid content in recent-onset type 1 and 2 diabetes mellitus. J Hepatol (2021) 74(5):1028−37. doi: 10.1016/j.jhep.2020.11.030
    1. Leeds JS, Forman EM, Morley S, Scott AR, Tesfaye S, Sanders DS. Abnormal liver function tests in patients with type 1 diabetes mellitus: prevalence, clinical correlations and underlying pathologies. Diabetes Med (2009) 26(12):1235–41. doi: 10.1111/j.1464-5491.2009.02839.x
    1. Singh-Franco D, Robles G, Gazze D. Pramlintide acetate injection for the treatment of type 1 and type 2 diabetes mellitus. Clin Ther (2007) 29(4):535–62. doi: 10.1016/j.clinthera.2007.04.005
    1. Liu W, Luo X, Tang J, Mo Q, Zhong H, Zhang H, et al. . A bridge for short-chain fatty acids to affect inflammatory bowel disease, type 1 diabetes, and non-alcoholic fatty liver disease positively: by changing gut barrier. Eur J Nutr (2021) 60(5):2317−30. doi: 10.1186/s12937-020-00660-7

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere