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Órgano Oficial de la Asociación Mexicana de Hepatología

2018, Number 4

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Ann Hepatol 2018; 17 (4)

Impact of Diabetes Mellitus and Insulin on Nonalcoholic Fatty Liver Disease in the Morbidly Obese

Strey CBM, de Carli LA, Pioner SR, Fantinelli M, Gobbato SS, Bassols GF, Losekann A, Coral GP

Language: English
References: 43
Page: 585-591
PDF size: 154.16 Kb.


ABSTRACT

Introduction and aim. The prevalence of obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease are increasing. Type 2 diabetes mellitus may aggravate non-alcoholic fatty liver disease, increasing the risk of developing cirrhosis and hepatocellular carcinoma. This study aims to determine the effect of type 2 diabetes mellitus and insulin therapy on non-alcoholic fatty liver disease in the patients with morbid obesity. Material and methods. Clinical, anthropometric and laboratory data were analyzed together with intraoperative liver biopsies from morbidly obese patients undergoing bariatric surgery. Results. 219 patients with morbid obesity were evaluated. Systemic arterial hypertension (55.9% vs. 33.8%, p = 0.004) and dyslipidemia (67.1% vs. 39.0%, p ‹ 0.001) were more prevalent in patients with diabetes when compared to patients without diabetes. In multivariate analysis, type 2 diabetes mellitus was an independent risk factor for severe steatosis (RR = 2.04, p = 0.023) and severe fibrosis (RR = 4.57, p = 0.013). Insulin therapy was significantly associated with non-alcoholic steatohepatitis (RR = 1.89, p = 0.001) and fibrosis (RR = 1.75, p = 0.050) when all patients were analysed, but when only patients with diabetes were analysed, insulin therapy was not associated with non-alcoholic steatohepatitis or fibrosis. Conclusion. Type 2 diabetes mellitus plays an important role in the progression of non-alcoholic fatty liver disease as an independent risk factor for severe fibrosis.


REFERENCES

  1. World Health Organization. Diabetes. [Internet]. Fact sheet no 312. Geneva: WHO; 2016 [reviewed 2016 June; cited 2016 June]. Available from: http://www.who.int/mediacentre/ factsheets/fs312/en/

  2. International Diabetes Federation. IDF Diabetes atlas [Internet]. 7th ed. Brussels: IDF; 2015 [cited 2016]. Available from: http://www.diabetesatlas.org/

  3. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015; 313: 2263-73.

  4. 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: 73-84.

  5. Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, Zein CO, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 2010; 52: 913-24.

  6. Wong VW, Wong GL, Choi PC, Chan AW, Li MK, Chan HY, Chim AM, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010; 59: 969-74.

  7. Losekann A, Weston AC, de Mattos AA, Tovo CV, de Carli LA, Espindola MB, Pioner SR, et al. Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients. Int J Mol Sci 2015; 16: 25552-9.

  8. Puchakayala BK, Verma S, Kanwar P, Hart J, Sanivarapu RR, Mohanty SR. Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease. World J Hepatol 2015; 7: 2610-8.

  9. Siddiqui MS, Patidar KR, Boyett S, Luketic VA, Puri P, Sanyal AJ. Performance of Non-invasive Models of Fibrosis in Predicting Mild to Moderate Fibrosis in Patients with Nonalcoholic Fatty Liver Disease (NAFLD). Liver Int 2015; 36: 572-9.

  10. Xia MF, Ling Y, Bian H, Lin HD, Yan HM, Chang XX, Li XM, et al. I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders. Aliment Pharmacol Ther 2016; 43: 631-42.

  11. Kontogianni MD, Tileli N, Margariti A, Georgoulis M, Deutsch M, Tiniakos D, Fragopoulou E, et al. Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutr 2014; 33: 678-83.

  12. Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein A. H. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr 2014; 100: 833-49.

  13. Bekaert M, Verhelst X, Geerts A, Lapauw B, Calders P. Association of recently described adipokines with liver histology in biopsy-proven non-alcoholic fatty liver disease: a systematic review. Obes Rev 2016; 17: 68-80.

  14. Savvidou S, Karatzidou K, Tsakiri K, Gagalis A, Hytiroglou P, Goulis J. Circulating adiponectin levels in type 2 diabetes mellitus patients with or without non-alcoholic fatty liver disease: Results of a small, open-label, randomized controlled intervention trial in a subgroup receiving short-term exenatide. Diabetes Res Clin Pract 2016; 113: 125-34.

  15. Lomonaco R, Ortiz-Lopez C, Orsak B, Webb A, Hardies J, Darland C, Finchi J, et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology 2012; 55: 1389-97.

  16. Lomonaco R, Bril F, Portillo-Sanchez P, Ortiz-Lopez C, Orsak B, Biernacki D, Lo M, et al. Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes. Diabetes Care 2016; 39: 632-8.

  17. Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, Guy CD, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 2016; 63: 764-75.

  18. Luther J, Garber JJ, Khalili H, Dave M, Bale SS, Jindal R, Motola DL, et al. Hepatic Injury in Nonalcoholic Steatohepatitis Contributes to Altered Intestinal Permeability. Cell Mol Gastroenterol Hepatol 2015; 1: 222- 32.

  19. Chattopadhyay M, Khemka VK, Chatterjee G, Ganguly A, Mukhopadhyay S, Chakrabarti S. Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Mol Cell Biochem 2015; 399: 95-103.

  20. Aouacheri O, Saka S, Krim M, Messaadia A, Maidi I. The investigation of the oxidative stress-related parameters in type 2 diabetes mellitus. Can J Diabetes 2015; 39: 44-9.

  21. Palem SP, Abraham P. A Study on the Level of Oxidative Stress and Inflammatory Markers in Type 2 Diabetes Mellitus Patients with Different Treatment Modalities. J Clin Diagn Res 2015; 9: BC04-7.

  22. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-23.

  23. Bower G, Toma T, Harling L, Jiao LR, Efthimiou E, Darzi A, Athanasiou T, et al. Bariatric Surgery and Non-Alcoholic Fatty Liver Disease: a Systematic Review of Liver Biochemistry and Histology. Obes Surg 2015; 25: 2280-9.

  24. Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, et al. Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology 2015; 149: 379-88.

  25. Möller K, Ostermann AI, Rund K, Thoms S, Blume C, Stahl F, Hahn A, et al. Influence of weight reduction on blood levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and oxylipins in obese subjects. Prostaglandins Leukot Essent Fatty Acids 2016; 106: 39-49.

  26. Marchesini G, Petta S, Dale Grave R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology 2016; 63: 2032-43.

  27. European Association for the Study of the Liver; European Association for the Study of Diabetes; European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388-402.

  28. World Health Organization. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. Geneva: WHO; 1995. WHO Technical Report Series No. 854.

  29. Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, Fonseca FA, et al. V Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. Arq Bras Cardiol 2013; 101: 1-20.

  30. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care 2016; 39: S1-109.

  31. Sociedade Brasileira de Cardiologia/Sociedade Brasileira de Hipertensão/Sociedade Brasileira de Nefrologia. VI Diretrizes Brasileiras de Hipertensão. Arq Bras Cardiol 2010; 95: 1-51.

  32. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-21.

  33. Yadav D, Mishra M, Joseph AZ, Subramani SK, Mahajan S, Singh N, Bisen PS, et al. Status of antioxidant and lipid peroxidation in type 2 diabetic human subjects diagnosed with and without metabolic syndrome by using NCEP-ATPIII, IDF and WHO criteria. Obes Res Clin Pract 2015; 9: 158-67.

  34. Van Dieren S, Kengne AP, Chalmers J, Beulens JW, Davis TM, Fulcher G, Heller SR, et al. Intensification of medication and glycaemic control among patients with type 2 diabetes - the ADVANCE trial. Diabetes Obes Metab 2014; 16: 426-32.

  35. Goh GB, Pagadala MR, Dasarathy J, Unalp-Arida A, Sargent R, Hawkins C, Sourianarayanane A, et al. Clinical spectrum of non-alcoholic fatty liver disease in diabetic and non-diabetic patients. BBA Clin 2014; 3: 141-5.

  36. Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol 2004; 2: 262-5.

  37. Bril F, Sninsky JJ, Baca AM, Robert Superko H, Portillo Sanchez P, Biernacki D, Maximos M, et al. Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD. J Clin Endocrinol Metab 2016; 101: 644-52.

  38. Boza C, Riquelme A, Ibañez L, Duarte I, Norero E, Viviani P, Soza A, et al. Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass. Obes Surg 2005; 15: 1148-53.

  39. Jung KY, Cho SY, Kim HJ, Kim SB, Song IH. Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to insulin resistance and liver histology. J Clin Gastroenterol 2014; 48: 883-8.

  40. Siddiqui MS, Cheang KL, Luketic VA, Boyett S, Idowu MO, Patidar K, Puri P, et al. Nonalcoholic Steatohepatitis (NASH) Is Associated with a Decline in Pancreatic Beta Cell (β-Cell) Function. Dig Dis Sci 2015; 60: 2529-37.

  41. Loomba R, Abraham M, Unalp A, Wilson L, Lavine J, Doo E, Bass NM, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 2012; 56: 943-51.

  42. Miyaaki H, Ichikawa T, Nakao K, Yatsuhashi H, Furukawa R, Ohba K, Omagari K, et al. Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis. Liver Int 2008; 28: 519-24.

  43. Musso G, Cassader M, Gambino R. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nat Rev Drug Discov 2016; 15: 249-74.




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