Addressing NAFLD as a Type 2 Diabetes Complication Using the Emerging Paradigms in Diagnostic and Management Techniques
Abstract
Several critical epidemiological facts underscore the urgent need to address non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D):
- NAFLD is the most common liver disease in Canada, affecting approximately one in four Canadians;
- NAFLD is projected to become the number one leading indication for liver transplant by 2025;
- Individuals with T2D are at the greatest risk of liver disease progression in NAFLD; T2D is the main predictor of NAFLD-related liver fibrosis and mortality.
To put this into clinical perspective, consider the following fictitious case: A 45-year-old teetotaler, Caucasian woman with T2D and a body mass index (BMI) of 32 kg/m2, with no microvascular or macrovascular complications, was incidentally found to have “fatty liver” on abdominal ultrasound. ALT and AST were both within normal range. She was recommended to lose weight and control A1C. Twelve years later, she developed hematemesis and liver biopsy confirmed end-stage liver cirrhosis, with hepatocellular carcinoma. She was scheduled to undergo a liver transplant at age 59.
Despite the three established facts presented above and an abundance of cases similar to the one presented here, currently NAFLD is not being addressed during routine diabetes care as a complication of T2D.
References
Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease: metaanalytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
Swain MGR, Patel, K, Sebastiani, G, et al. NAFLD Disease Burden - Canada, 2019-2030: a modeling study. CMAJ Open 2020. 8(2):E429-36.
Wong RJ, Aguilar M, Cheung R, , et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 2015;148:547-555.
Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 2017;65:1557-1565.
Loomba, R, Abraham, M, Unalp, A, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 2012;56:943-951.
Sebastiani GR, Swain, MG, Patel, K. A Canadian survey on knowledge of non-alcoholic fatty liver disease among physicians. Canadian Liver Journal 2021;4(2):82-92.
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;67:328-357.
Introduction: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019;42:S1-S2.
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;64:1388-1402.
Kanwal F, Shubrook JH, Adams LA, et al. Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease. Gastroenterology. 2021;161(5):1657-1669.
Koutoukidis DA, Koshiaris C, Henry JA, et al. The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism 2021;115:154455.
Baldwin D, Chennakesavalu M, Gangemi A. Systematic review and meta-analysis of Roux-en-Y gastric bypass against laparoscopic sleeve gastrectomy for amelioration of NAFLD using four criteria. Surg Obes Relat Dis 2019;15:2123-2130.
Newsome PN, Buchholtz K, Cusi K, et al. A placebo controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med 2021;384:1113-1124.
Eriksson JW, Lundkvist P, Jansson PA, et al. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia 2018;61:1923-1934.
Kahl S, Gancheva S, Straßburger K, et al. Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo controlled trial. Diabetes Care 2020;43:298-305.
Musso G, Cassader M, Paschetta E, et al. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med 2017;177:633–640.
Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. The Lancet. 2019;394(10215):2184-2196.
Madrigal Pharmaceuticals Inc. Madrigal announces additional positive results from the pivotal Phase 3 MAESTRO-NASH clinical trial of Resmetirom for the treatment of NASH with liver fibrosis. Globe Newswire. 6 Jan 2023 [accessed 18 Feb 2023]. https://www.globenewswire.com/news-release/2023/01/06/2584391/0/en/Madrigal-Announces-Additional-Positive-Results-from-the-Pivotal-Phase-3-MAESTRO-NASH-Clinical-Trial-of-Resmetirom-for-the-Treatment-of-NASH-with-Liver-Fibrosis.
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Canadian Diabetes & Endocrinology Today
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
