Evaluation of Insulin Resistance of Individuals with MAFLD

Öz

Introduction: MAFLD is a new diagnosis that has been brought to the terminology in the last 2 years, and it is thought that the main mechanism underlying its development is Insulin Resistance (IR). In our study, it is planned to research the role of IR level in the etiology of patients with MAFLD. Method: 265 individuals with MAFLD are included in the study by examining their sub-parameters of case diagnosis. While 85 patients have T2DM, 180 patients are found to be Prediabetic. IR is calculated with HOMA-IR. The value of 2.5 and above is considered as high, and below 2.5 is considered as normal. The ratios of HOMA-IR levels and their relationship between waist circumference and BMI were examined. Findings: The value of HOMA-IR was found high in 60.6% of prediabetic MAFLDs, while it was normal in 39.4% of them. Age ((p=0.001; p<0.01) and waist circumference (p=0.028; p<0.05) in the T2DM group were found to be higher than the prediabetic group. Very weak positive correlation was found between HOMA-IR and BMI (r=0.223; p=0.003; p<0.01) and waist circumference (r=0.205; p=0.006; p<0.01) in the prediabetic group. In the T2DM group, there was a very weak positive correlation between BMI and HOMA-IR (r=0.254; p=0.019; p<0.05). Conclusion: In our study, IR was not detected in 39.4% of patients with MAFLD. This result leads us to think that insulin sensitizing agents may not be effective in this patient group in patients with normal IR levels. We think that these agents will not be effective in patients with normal IR levels. Our study should be supported with experimental and histological MAFLD studies.

Anahtar Kelimeler

• MAFLD
• Prediabetes
• Insulin Resistance

MAFLD’lı Bireylerin İnsülin Rezistansı’nın Değerlendirilmesi

Öz

Giriş: MAFLD son 2 yılda terminolojiye kazandırılmış yeni bir tanı olup, gelişiminde altta yatan ana mekanizmanın İnsülin Rezistansı(IR) olduğu düşünülmektedir. Çalışmamızla MAFLD’lı hastaların IR düzeyinin etyolojideki rolünü incelemeyi planladık. Method: Çalışmaya 265 MAFLD’lı vaka tanı alt parametreleri incelenerek dahil edildi. 85 hastada T2DM varken, 180 hasta Prediyabetik’ti. HOMA-IR ile IR hesaplandı. 2.5 ve üzeri yüksek, 2.5 altı normal olarak değerlendirildi. HOMA-IR düzeyi oranları ve bel çevresi ve BMI ile ilişkisi incelendi. Bulgular: Prediyabetik MAFLD’ların %60.6’sında HOMA-IR yüksek iken, %39.4’ünde normaldir. T2DM grubunun yaş((p=0,001; p<0,01) ve bel çevresi(p=0,028; p<0,05) prediyabetik gruptan yüksek tespit edildi. Prediyabetik grupta HOMA-IR ile BMI arasında(r=0,223; p=0,003; p<0,01), bel çevresi arasında(r=0,205; p=0,006; p<0,01) çok zayıf pozitif ilişki tespit edilmiştir. T2DM grubunda ise BMI ile HOMA-IR arasında çok zayıf düzeyde pozitif ilişki tespit edilmiştir(r=0,254; p=0,019; p<0,05). Sonuç: Çalışmamızda MAFLD’lı hastaların %39.4’ünde IR saptanmamıştır. Bu sonuç bize IR düzeyi normal hastalarda insülin duyarlaştırıcı ajanların bu hasta grubunda işe yaramayabileceğini düşündürmektedir. IR seviyesi normal hastalarda bu ajanların işe yaramayacağını düşünmekteyiz. Çalışmamızın deneysel ve histolojik düzeyde MAFLD çalışmaları ile desteklenmesi gerekmektedir.

Anahtar Kelimeler

• MAFLD
• İnsülin Rezistansı
• Prediyabet

Kaynakça

1. Sanyal AJ. Past, present and future perspectives in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2019;16(6):377–386. doi: 10.1038/s41575-019-0144-8.
2. Eslam M, Sanyal AJ, George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020; 158:1999–2014. doi: 10.1053/j.gastro.2019.11.312.
3. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol 2020;73:202-209. doi: https://doi.org/10.1016/j.jhep.2020.03.039.
4. Cusi K, Sanyal AJ, Zhang S, Hartman ML, Bue-Valleskey JM, Hoogwerf BJ, et al. Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. Diabetes Obes Metab 2017; 19:1630–1634. doi: 10.1111/dom.12973.
5. Vilela BS, Vasques AC, Cassani RS, Forti AC, Pareja JC, Tambascia MA; BRAMS Investigators, Geloneze B. The HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS). PLoS One. 2016 Aug 4;11(8):e0158751. doi: 10.1371/journal.pone.0158751. PMID: 27490249; PMCID: PMC4973901.
6. Hossain IA, Rahman Shah MM, Rahman MK, Ali L. Gamma glutamyl transferase is an independent determinant for the association of insulin resistance with nonalcoholic fatty liver disease in Bangladeshi adults: Association of GGT and HOMA-IR with NAFLD. Diabetes Metab Syndr. 2016 Jan-Mar;10(1 Suppl 1):S25-9. doi: 10.1016/j.dsx.2015.09.005. Epub 2015 Oct 9. PMID: 26482965.
7. Isokuortti E, Zhou Y, Peltonen M, Bugianesi E, Clement K, Bonnefont-Rousselot D, Lacorte JM, Gastaldelli A, Schuppan D, Schattenberg JM, Hakkarainen A, Lundbom N, Jousilahti P, Männistö S, Keinänen-Kiukaanniemi S, Saltevo J, Anstee QM, Yki-Järvinen H. Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study. Diabetologia. 2017 Oct;60(10):1873-1882. doi: 10.1007/s00125-017-4340-1. Epub 2017 Jun 29. PMID: 28660493.
8. Lin S, Huang J, Wang M, Kumar R, Liu Y, Liu S, Wu Y, Wang X, Zhu Y. Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver Int. 2020 Sep;40(9):2082-2089. doi: 10.1111/liv.14548. Epub 2020 Jul 26. PMID: 32478487.

9. Giannarelli R, Aragona M, Coppelli A, Del Prato S. Reducing insulin resistance with metformin: the evidence today. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S28-35. doi: 10.1016/s1262-3636(03)72785-2. PMID: 14502098.
10. Şenyiğit, A., & Kanat, M. (2017). Physiopathological treatment approach and position of pioglitazone in type 2 diabetes. Anatolian Clinic the Journal of Medical Sciences, 22(3), 220-223. https://doi.org/10.21673/anadoluklin.284462
11. Della Pepa G, Russo M, Vitale M, Carli F, Vetrani C, Masulli M, Riccardi G, Vaccaro O, Gastaldelli A, Rivellese AA, Bozzetto L. Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial. Diabetes Res Clin Pract. 2021 Aug;178:108984. doi: 10.1016/j.diabres.2021.108984. Epub 2021 Jul 24. PMID: 34311022.
12. Xu P, Zhang XG, Li YM, Yu CH, Xu L, Xu GY. Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats. J Zhejiang Univ Sci B. 2006 Aug;7(8):627-33. doi: 10.1631/jzus.2006.B0627. PMID: 16845716; PMCID: PMC1533756.
13. Jalali M, Rahimlou M, Mahmoodi M, Moosavian SP, Symonds ME, Jalali R, et al. The effects of metformin administration on liver enzymes and body composition in non-diabetic patients with nonalcoholic fatty liver disease and/or non-alcoholic steatohepatitis: an up-to date systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2020;159:104799. doi: https://doi.org/10.1016/j.phrs.2020.104799.
14. Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012; 55:885-904. doi: https://doi.org/10.1007/s00125-011-2446-4.
15. Lobstein, Tim, Hannah Brinsden, and Margot Neveux. "World Obesity Atlas 2022." (2022).
16. Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag N, Karsidag K, Genc S, Telci A, Canbaz B, Turker F, Yilmaz T, Cakir B, Tuomilehto J; TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013 Feb;28(2):169-80. doi: 10.1007/s10654-013-9771-5. Epub 2013 Feb 14. PMID: 23407904; PMCID: PMC3604592.
17. Sengul S, Akpolat T, Erdem Y, Derici U, Arici M, Sindel S, Karatan O, Turgan C, Hasanoglu E, Caglar S, Erturk S; Turkish Society of Hypertension and Renal Diseases. Changes in hypertension prevalence, awareness, treatment, and control rates in Turkey from 2003 to 2012. J Hypertens. 2016 Jun;34(6):1208-17. doi: 10.1097/HJH.0000000000000901. PMID: 26991534; PMCID: PMC4856172.