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Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism

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Abstract

Non-alcoholic fatty liver disease is mostly associated with diabetes mellitus. Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent. However, its effects on liver fat and pancreatic fat contents are not evaluated yet. The objectives of the study were to evaluate the effects of dulaglutide on liver fat content, pancreatic fat content, liver stiffness, and liver enzyme levels. Patients have taken 0.75 mg subcutaneous dulaglutide each week for 4 weeks, then 1.5 mg weekly for 20 weeks plus standard treatment (metformin plus sulfonylurea and/or insulin; DS group, n = 25), or patients have taken standard treatment (metformin plus sulfonylurea and/or insulin) alone (ST group, n = 46) for type 2 diabetes management. Both groups reported a decrease in liver fat content, pancreatic fat content, and liver stiffness after interventions (p < 0.001 for all). After interventions, the DS group reported a higher decrease in liver fat content, pancreatic fat content, and liver stiffness than that of the ST group (p < 0.001 for all). After interventions, the DS group reported a higher decrease in body mass index than that of the ST group (p < 0.05). There were significant improvements in liver function tests, kidney function tests, lipid profiles, and blood counts after interventions (p < 0.05 for all). Both groups reported a decrease in body mass index after interventions (p < 0.001 for both). The DS group significantly decrease body mass index after interventions (p < 0.05) than the ST group.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Ahmed, B., & Ali, A. (2021). Usage of traditional Chinese medicine, western medicine and integrated Chinese-western medicine for the treatment of allergic rhinitis. SPR, 1(1), 1–10.

    Article  Google Scholar 

  2. Al Fath, A. M., & Harun, S. (2021 [cited 2022 Oct. 18]). The impact of educational practices in learning comics and video media on social science subjects as alternatives in a pandemic period. kuey, 27(3), 1125–1132.

    Article  Google Scholar 

  3. American Diabetes Association. (2018). Glycemic targets: Standards of medical care in diabetes-2018. Diabetes Care, 41(Suppl 1), S55–S64.

    Article  Google Scholar 

  4. Armstrong, M. J., Gaunt, P., Aithal, G. P., Barton, D., Hull, D., Parker, R., Hazlehurst, J. M., Guo, K., LEAN trial team, Abouda, G., Aldersley, M. A., Stocken, D., Gough, S. C., Tomlinson, J. W., Brown, R. M., Hübscher, S. G., & Newsome, P. N. (2016). Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet, 387(10019), 679–690.

    Article  CAS  PubMed  Google Scholar 

  5. Bouchi, R., Nakano, Y., Fukuda, T., Takeuchi, T., Murakami, M., Minami, I., Izumiyama, H., Hashimoto, K., Yoshimoto, T., & Ogawa, Y. (2017). Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: A randomized control trial. Endocrine Journal, 64(3), 269–281.

    Article  CAS  PubMed  Google Scholar 

  6. Cusi, K., Sattar, N., García-Pérez, L. E., Pavo, I., Yu, M., Robertson, K. E., Karanikas, C. A., & Haupt, A. (2018). Dulaglutide decreases plasma aminotransferases in people with type 2 diabetes in a pattern consistent with liver fat reduction: A post hoc analysis of the AWARD programme. Diabetic Medicine, 35(10), 1434–1439.

    Article  CAS  PubMed  Google Scholar 

  7. Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S., & Hultcrantz, R. (2015). Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology, 61(5), 1547–1554.

    Article  CAS  PubMed  Google Scholar 

  8. Meriç, E., & Erdem, M. (2021). Prediction of professional commitment of teachers by the job characteristics of teaching profession. kuey, 26(2), 449–494.

    Google Scholar 

  9. Fala, L. (2015). Trulicity (dulaglutide): A new GLP-1 receptor agonist once-weekly subcutaneous injection approved for the treatment of patients with type 2 diabetes. American Health and Drug Benefits, 8(Spec Feature), 131–134.

    PubMed  PubMed Central  Google Scholar 

  10. Gerstein, H. C., Colhoun, H. M., Dagenais, G. R., Diaz, R., Lakshmanan, M., Pais, P., Probstfield, J., Riesmeyer, J. S., Riddle, M. C., Rydén, L., Xavier, D., Atisso, C. M., Dyal, L., Hall, S., Rao-Melacini, P., Wong, G., Avezum, A., Basile, J., Chung, N., et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet, 394(10193), 121–130.

    Article  CAS  PubMed  Google Scholar 

  11. Ghosal, S., Datta, D., & Sinha, B. (2021). A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D). Scientific Reports, 11(1), 22063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gupta, R., Gupta, P., Gupta, S., & Garg, S. (2021). Comparative evaluation to determine the efficacy of conventional radiography, digital radiography and ultrasound imaging in the diagnosis of periapical lesions. SPR, 1(3), 160–165.

    Article  Google Scholar 

  13. He, Q., Sha, S., Sun, L., Zhang, J., & Dong, M. (2016). GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway. Biochemical and Biophysical Research Communications, 476(4), 196–203.

    Article  CAS  PubMed  Google Scholar 

  14. Kawaguchi, T., Itou, M., Taniguchi, E., & Sata, M. (2014). Exendin-4, a glucagon-like peptide-1 receptor agonist, modulates hepatic fatty acid composition and Δ-5-desaturase index in a murine model of non-alcoholic steatohepatitis. International Journal of Molecular Medicine, 34(3), 782–787.

    Article  CAS  PubMed  Google Scholar 

  15. Kuchay, M. S., Krishan, S., Mishra, S. K., Choudhary, N. S., Singh, M. K., Wasir, J. S., Kaur, P., Gill, H. K., Bano, T., Farooqui, K. J., & Mithal, A. (2020). Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: Randomised controlled trial (D-LIFT trial). Diabetologia, 63(11), 2434–2445.

    Article  CAS  PubMed  Google Scholar 

  16. Kuchay, M. S., Krishan, S., Mishra, S. K., Farooqui, K. J., Singh, M. K., Wasir, J. S., Bansal, B., Kaur, P., Jevalikar, G., Gill, H. K., Choudhary, N. S., & Mithal, A. (2018). Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: A randomized controlled trial (E-LIFT trial). Diabetes Care, 41(8), 1801–1808.

    Article  CAS  PubMed  Google Scholar 

  17. Lee, J., Hong, S. W., Chae, S. W., Kim, D. H., Choi, J. H., Bae, J. C., Park, S. E., Rhee, E. J., Park, C. Y., Oh, K. W., Park, S. W., Kim, S. W., & Lee, W. Y. (2012). Exendin-4 improves steatohepatitis by increasing Sirt1 expression in high-fat diet-induced obese C57BL/6J mice. PLoS One, 7(2), e31394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Li, Z., Zhang, Y., Quan, X., Yang, Z., Zeng, X., Ji, L., Sun, F., & Zhan, S. (2016). Efficacy and acceptability of glycemic control of glucagon-like peptide-1 receptor agonists among type 2 diabetes: A systematic review and network meta-analysis. PLoS One, 11(5), e0154206.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Mells, J. E., Fu, P. P., Sharma, S., Olson, D., Cheng, L., Handy, J. A., Saxena, N. K., Sorescu, D., & Anania, F. A. (2012). Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. American Journal of Physiology. Gastrointestinal and Liver Physiology, 30(2), G225–G235.

    Article  Google Scholar 

  20. Moreira, G. V., Azevedo, F. F., Ribeiro, L. M., Santos, A., Guadagnini, D., Gama, P., Liberti, E. A., Saad, M., & Carvalho, C. (2018). Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. The Journal of Nutritional Biochemistry, 62, 143–154.

    Article  CAS  PubMed  Google Scholar 

  21. Muthmainnah, O., & Khalaf, H. A. (2022). Adoption social media-movie based learning project (SMMBL) to engage students’ online environment. Educational Administration: Theory and Practice, 28(1), 22–36. https://doi.org/10.17762/kuey.v28i01.321

    Article  Google Scholar 

  22. Nelmira, W., Efi, A., Elida, A., & Sandra, Y. (2022). Efforts to develop creativity in vocational education through a learning model based on student research activities. Educational Administration: Theory and Practice, 28(1), 1–9. https://doi.org/10.17762/kuey.v28i01.319

    Article  Google Scholar 

  23. Noureddin, M., Lam, J., Peterson, M. R., Middleton, M., Hamilton, G., Le, T. A., Bettencourt, R., Changchien, C., Brenner, D. A., Sirlin, C., & Loomba, R. (2013). Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology, 58(6), 1930–1940.

    Article  CAS  PubMed  Google Scholar 

  24. Nwuke, C., & Ibeh, B. (2021). Antidiarrheal potential of methanol extract of Combretum dolichopetalum and its fractions in Wistar albino rats. SPR, 1(1), 11–23.

    Article  Google Scholar 

  25. Petit, J. M., Cercueil, J. P., Loffroy, R., Denimal, D., Bouillet, B., Fourmont, C., Chevallier, O., Duvillard, L., & Vergès, B. (2017). Effect of liraglutide therapy on liver fat content in patients with inadequately controlled type 2 diabetes: The Lira-NAFLD study. The Journal of Clinical Endocrinology and Metabolism, 102(2), 407–415.

    PubMed  Google Scholar 

  26. Piegu, M. K. A., Yakubu, F. J., Kudese, T. Y., & Fokuoh, P. A. (2021). Effects of Nordox 75 WG on the health quality of tomatoes. SPR, 1(3), 182–190.

    Article  Google Scholar 

  27. Rasheed Al-Khafaji, A. H. A. (2022). The effect of tests of higher levels of the cognitive domain in preventing mass electronic fraud in distance education. Educational Administration: Theory and Practice, 28(1), 10–21. https://doi.org/10.17762/kuey.v28i01.320

    Article  Google Scholar 

  28. Sharma, S., Mells, J. E., Fu, P. P., Saxena, N. K., & Anania, F. A. (2011). GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLoS One, 6(9), e25269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Singh, R., & Bahadur, A. (2021). Gender differences in spirituality and subjective well-being among working couples in Indian society. SPR, 1(3), 177–181.

    Article  Google Scholar 

  30. Siraj, I., & Bharti, P. S. (2021). 3D printing process: A review of recent research. SPR, 1(3), 166–176.

    Article  Google Scholar 

  31. Smits, M. M., Tonneijck, L., Muskiet, M. H., Kramer, M. H., Pouwels, P. J., Pieters-van den Bos, I. C., Hoekstra, T., Diamant, M., van Raalte, D. H., & Cahen, D. L. (2016). Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: A randomised placebo-controlled trial. Diabetologia, 59(12), 2588–2593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tang, A., Rabasa-Lhoret, R., Castel, H., Wartelle-Bladou, C., Gilbert, G., Massicotte-Tisluck, K., Chartrand, G., Olivié, D., Julien, A. S., de Guise, J., Soulez, G., & Chiasson, J. L. (2015). Effects of insulin glargine and liraglutide therapy on liver fat as measured by magnetic resonance in patients with type 2 diabetes: A randomized trial. Diabetes Care, 38(7), 1339–1346.

    Article  CAS  PubMed  Google Scholar 

  33. Trevaskis, J. L., Griffin, P. S., Wittmer, C., Neuschwander-Tetri, B. A., Brunt, E. M., Dolman, C. S., Erickson, M. R., Napora, J., Parkes, D. G., & Roth, J. D. (2012). Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. American Journal of Physiology. Gastrointestinal and Liver Physiology, 302(8), G762–G772.

    Article  CAS  PubMed  Google Scholar 

  34. Tuncer Fidan; Mehmet Hilmi Koç. (2021). Teachers’ opinions on ethical and unethical leadership: A phenomenological research. Kuey., 26(2), 355–400.

    Google Scholar 

  35. Wong, V. W., Wong, G. L., Yeung, D. K., Abrigo, J. M., Kong, A. P., Chan, R. S., Chim, A. M., Shen, J., Ho, C. S., Woo, J., Chu, W. C., & Chan, H. L. (2014). Fatty pancreas, insulin resistance, and β-cell function: A population study using fat-water magnetic resonance imaging. The American Journal of Gastroenterology, 109(4), 589–597.

    Article  CAS  PubMed  Google Scholar 

  36. Wu, W. C., & Wang, C. Y. (2013). Association between non-alcoholic fatty pancreatic disease (NAFPD) and the metabolic syndrome: Case-control retrospective study. Cardiovascular Diabetology, 12, 77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhou, J. Y., Poudel, A., Welchko, R., Mekala, N., Chandramani-Shivalingappa, P., Rosca, M. G., & Li, L. (2019). Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways. European Journal of Pharmacology, 861, 172594.

    Article  CAS  PubMed  Google Scholar 

  38. Zhu, W., Feng, P. P., He, K., Li, S. W., & Gong, J. P. (2018). Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet. Biochemical and Biophysical Research Communications, 505(2), 523–529.

    Article  CAS  PubMed  Google Scholar 

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Funding

Effects of semaglutide on pancreatic fat content and pancreatic β-cell function in obese patients with type 2 diabetes mellitus (item number2022-3-080).

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Authors and Affiliations

  1. Jinhua Municipal Central Hospital, Department of Endocrinology, Jinhua, 321000, China

    Huaying Huang, Heye Chen & Yanfen Liu

  2. Jinhua Municipal Central Hospital, Department of Neurology, Jinhua, 321000, China

    Shuihong Zheng

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The SL confirms sole responsibility for the following: study conception and design, data collection, analysis and interpretation of results, and manuscript preparation.

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Correspondence to Shuihong Zheng.

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Zheng, S., Huang, H., Chen, H. et al. Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism. Appl Biochem Biotechnol 195, 5238–5251 (2023). https://doi.org/10.1007/s12010-023-04505-x

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