Advanced Biomedical Research

Association of subclinical hypothyroidism with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: A cross-sectional study

Document Type : Original Article

Authors

1 Department of Pediatric Nephrology, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Endocrinology and Metabolism, Zahedan University of Medical Sciences, Zahedan, Iran

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are recognized as two common health problems. Metabolic diseases, such as dyslipidemia, obesity, and hypertension are known risk factors for NAFLD. In addition to these risk factors, other risk factors have been recently suggested, such as thyroid dysfunction.
Materials and Methods: In this study, adult patients with T2DM were recruited. Various clinical and biochemical parameters including thyroid function tests, liver function tests, and liver sonography in all participants were assessed and compared between with and without NAFLD groups.
Results: Data from 926 diabetic patients were analyzed; of which, 744 (80.3%) had fatty liver. The prevalence of subclinical hypothyroidism (SCH) in patients with NAFLD was 11.6% and in patients without NAFLD was 6.0% (P = 0.029). Furthermore, the prevalence of overt hypothyroidism was higher in diabetic patients with NAFLD (3.9% vs. 1.6%); this difference was not statistically significant. In univariate logistic regression analysis, hemoglobin A1c (odds ratio [OR]: 8.13); history of insulin consumption (OR: 5.35); duration of diabetes (OR: 2.20); family history of diabetes (OR: 2.85); history of antihypertensive drug use (OR: 2.14) as well as SCH (OR: 2.03) were significant variables for NAFLD. According to the multivariate logistic model, after eliminating the confounding effect of age, sex, and body mass index; the chance of developing NAFLD in patients with SCH was 2.32 times higher than patients without SCH (P = 0.014).
Conclusion: NAFLD is extremely common in patients with T2DM. The relationship between hypothyroidism and NAFLD is independent of other risk factors.

Keywords

1.
Aller R, Fernández-Rodríguez C, Lo Iacono O, Bañares R, Abad J, Carrión JA, et al. Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline. Gastroenterol Hepatol 2018;41:328-49.  Back to cited text no. 1
    
2.
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;67:328-57.  Back to cited text no. 2
    
3.
Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World J Gastroenterol 2018;24:3361-73.  Back to cited text no. 3
    
4.
Samji NS, Verma R, Satapathy SK. Magnitude of nonalcoholic fatty liver disease: Western perspective. J Clin Exp Hepatol 2019;9:497-505.  Back to cited text no. 4
    
5.
Andronescu CI, Purcarea MR, Babes PA. Nonalcoholic fatty liver disease: Epidemiology, pathogenesis and therapeutic implications. J Med Life 2018;11:20-3.  Back to cited text no. 5
    
6.
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;23:8263-76.  Back to cited text no. 6
    
7.
Iqbal U, Perumpail BJ, Akhtar D, Kim D, Ahmed A. The epidemiology, risk profiling and diagnostic challenges of nonalcoholic fatty liver disease. Medicines (Basel) 2019;6:41.  Back to cited text no. 7
    
8.
Duseja A, Dhiman RK, Premkumar M. Nonalcoholic fatty liver disease: Lessons learnt in the last five years. J Clin Exp Hepatol 2021;11:159-62.  Back to cited text no. 8
    
9.
Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019;157:107843.  Back to cited text no. 9
    
10.
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;71:793-801.  Back to cited text no. 10
    
11.
Kitade H, Chen G, Ni Y, Ota T. Nonalcoholic fatty liver disease and insulin resistance: New insights and potential new treatments. Nutrients 2017;9:387.  Back to cited text no. 11
    
12.
Khan RS, Bril F, Cusi K, Newsome PN. Modulation of insulin resistance in nonalcoholic fatty liver disease. Hepatology 2019;70:711-24.  Back to cited text no. 12
    
13.
Fujii H, Kawada N, Japan Study Group Of Nafld Jsg-Nafld. The role of insulin resistance and diabetes in nonalcoholic fatty liver disease. Int J Mol Sci 2020;21:3863.  Back to cited text no. 13
    
14.
Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The liver as an endocrine organ-linking NAFLD and insulin resistance. Endocr Rev 2019;40:1367-93.  Back to cited text no. 14
    
15.
Lei Y, Yang J, Li H, Zhong H, Wan Q. Changes in glucose-lipid metabolism, insulin resistance, and inflammatory factors in patients with autoimmune thyroid disease. J Clin Lab Anal 2019;33:e22929.  Back to cited text no. 15
    
16.
Delitala AP, Fanciulli G, Maioli M, Delitala G. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease. Eur J Intern Med 2017;38:17-24.  Back to cited text no. 16
    
17.
Gutch M, Rungta S, Kumar S, Agarwal A, Bhattacharya A, Razi SM. Thyroid functions and serum lipid profile in metabolic syndrome. Biomed J 2017;40:147-53.  Back to cited text no. 17
    
18.
Jung KY, Ahn HY, Han SK, Park YJ, Cho BY, Moon MK. Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function. J Clin Lipidol 2017;11:1347-53.  Back to cited text no. 18
    
19.
Parikh P, Phadke A, Sawant P. Prevalence of hypothyroidism in nonalcoholic fatty liver disease in patients attending a tertiary hospital in western India. Indian J Gastroenterol 2015;34:169-73.  Back to cited text no. 19
    
20.
Kim D, Vazquez-Montesino LM, Escober JA, Fernandes CT, Cholankeril G, Loomba R, et al. Low thyroid function in nonalcoholic fatty liver disease is an independent predictor of all-cause and cardiovascular mortality. Am J Gastroenterol 2020;115:1496-504.  Back to cited text no. 20
    
21.
Petersmann A, Müller-Wieland D, Müller UA, Landgraf R, Nauck M, Freckmann G, et al. Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes 2019;127:S1-7.  Back to cited text no. 21
    
22.
Ferraioli G, Soares Monteiro LB. Ultrasound-based techniques for the diagnosis of liver steatosis. World J Gastroenterol 2019;25:6053-62.  Back to cited text no. 22
    
23.
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, 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.  Back to cited text no. 23
    
24.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017;390:2627-42.  Back to cited text no. 24
    
25.
NCD Risk Factor Collaboration (NCD-RisC) – Africa Working Group. Trends in obesity and diabetes across Africa from 1980 to 2014: An analysis of pooled population-based studies. Int J Epidemiol 2017;46:1421-32.  Back to cited text no. 25
    
26.
Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: A meta-analysis. Diabetes Care 2018;41:372-82.  Back to cited text no. 26
    
27.
Bano A, Chaker L, Plompen EP, Hofman A, Dehghan A, Franco OH, et al. Thyroid function and the risk of nonalcoholic fatty liver disease: The Rotterdam study. J Clin Endocrinol Metab 2016;101:3204-11.  Back to cited text no. 27
    
28.
Xu L, Ma H, Miao M, Li Y. Impact of subclinical hypothyroidism on the development of non-alcoholic fatty liver disease: A prospective case-control study. J Hepatol 2012;57:1153-4.  Back to cited text no. 28
    
29.
Bril F, Kadiyala S, Portillo Sanchez P, Sunny NE, Biernacki D, Maximos M, et al. Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes. J Investig Med 2016;64:63-8.  Back to cited text no. 29
    
30.
Lee KW, Bang KB, Rhee EJ, Kwon HJ, Lee MY, Cho YK. Impact of hypothyroidism on the development of non-alcoholic fatty liver disease: A 4-year retrospective cohort study. Clin Mol Hepatol 2015;21:372-8.  Back to cited text no. 30
    
31.
Lonardo A, Ballestri S, Mantovani A, Nascimbeni F, Lugari S, Targher G. Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity? Dig Liver Dis 2019;51:462-70.  Back to cited text no. 31
    
32.
Sinha RA, Singh BK, Yen PM. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol 2018;14:259-69.  Back to cited text no. 32
    
33.
Lugari S, Mantovani A, Nascimbeni F, Lonardo A. Hypothyroidism and nonalcoholic fatty liver disease – A chance association? Horm Mol Biol Clin Investig 2018;41:47-51.  Back to cited text no. 33
    
34.
Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017;390:1550-62.  Back to cited text no. 34
    
35.
Lonardo A, Nascimbeni F, Mantovani A, Targher G. Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? J Hepatol 2018;68:335-52.  Back to cited text no. 35
    
36.
Danford CJ, Lai M. NAFLD: A multisystem disease that requires a multidisciplinary approach. Frontline Gastroenterol 2019;10:328-9.  Back to cited text no. 36
    
37.
Bril F, Kadiyala S, Cusi K. Re: “Association between primary hypothyroidism and nonalcoholic fatty liver disease: A systematic review and meta-analysis” by Mantovani et al. (Thyroid 2018;28:1270-1284). Thyroid 2019;29:452.  Back to cited text no. 37
    
38.
Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology 2019;156:1264-81.e4
Advanced Biomedical Research
Volume 2022, December
December 2022
Pages 1-7